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Cirrhosis File - Related Information
Cirrhosis File
Patients all over the world have used the information in The Cirrhosis File since 1992, when the Center for Current Research—one of the first 80 companies on the Internet—was founded. Their highly trained researchers (all of whom hold Ph.D.s) have searched the advanced medical database at the National Library of Medicine and compiled a comprehensive collection of research descriptions on Cirrhosis and its care.
The following research descriptions detail the findings published in the most respected journals in the field. Because the research descriptions are written in medical terms, you may come across them in your medical transcription.
We at ProfitMTFuture medical transcription education/medical word editing education are hoping this compilation of articles on cirrhosis will be helpful to you if you come across some of these terms. We commend you in your medical transcription education search for terms! Medical transcriptionists, good ones, really become detectives! See the American Association for Medical transcription site regarding great qualities for medical transcriptionists: http://www.aamt.org/scriptcontent/rjobdesc.cfm
Welcome to the Cirrhosis File
Patients all over the world
have used the information in The Cirrhosis File since 1992, when
the Center for Current Research—one of the first 80 companies
on the Internet—was founded. Our highly trained researchers
(all of whom hold Ph.D.s) have searched the advanced medical
database at the National Library of Medicine and compiled a comprehensive
collection of research descriptions on Cirrhosis and its care.
As you will see, the following research descriptions detail the
findings published in the most respected journals in the field.
Because the research descriptions are written in medical terms,
most people will bring all or parts of the Cirrhosis File to
their doctor for further explanation and discussion. Often your
doctor will have access to full-text articles and other information
that could be useful in planning a successful course of treatment
and prevention. Note that the titles of the journals are abbreviated
according to the National Library of Medicine's format; your
doctor can provide the full title if you need it.
Thank you for accessing the Cirrhosis File. We truly hope the
information fosters better health.
Sincerely,
Gregory A. Fraser, Ph.D.
Director of Research
Cirrhosis File - Related Information
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Latest Research on Cirrhosis
Cardiovasc Intervent Radiol. 2006 Sep-Oct;29(5):785-90.
Transjugular intrahepatic portosystemic shunt placement in
patients with cirrhosis and concomitant portal vein thrombosis.
Van Ha TG, Hodge J, Funaki B, Lorenz J, Rosenblum J, Straus C, Leef J.
Department of Radiology, Section of Interventional Radiology, The University of
Chicago, 5841 South Maryland Avenue MC 2026, Chicago, IL 60637, USA. tgvanha@radiology.bsd.uchicago.edu
PURPOSE: To determine the safety and efficacy of transjugular intrahepatic
portosystemic shunt (TIPS) creation in patients with liver cirrhosis complicated
by thrombosed portal vein. METHODS: This study reviewed 15 cases of TIPS
creation in 15 cirrhotic patients with portal vein thrombosis at our institution
over an 8-year period. There were 2 women and 13 men with a mean age of 53
years. Indications were refractory ascites, variceal hemorrhage, and refractory
pleural effusion. Clinical follow-up was performed in all patients. RESULTS: The
technical success rate was 75% (3/4) in patients with chronic portal vein
thrombosis associated with cavernomatous transformation and 91% (10/11) in
patients with acute thrombosis or partial thrombosis, giving an overall success
rate of 87%. Complications included postprocedural encephalopathy and localized
hematoma at the access site. In patients with successful shunt placement, the
total follow-up time was 223 months. The 30-day mortality rate was 13%. Two
patients underwent liver transplantation at 35 days and 7 months, respectively,
after TIPS insertion. One patient had an occluded shunt at 4 months with an
unsuccessful revision. The remaining patients had functioning shunts at
follow-up. CONCLUSION: TIPS creation in thrombosed portal vein is possible and
might be a treatment option in certain patients.
Endoscopy. 2006 Sep;38(9):896-901.
The use of self-expanding metal stents to treat acute esophageal
variceal bleeding.
Hubmann R, Bodlaj G, Czompo M, Benko L, Pichler P, Al-Kathib S, Kiblbock P,
Shamyieh A, Biesenbach G.
2nd Dept. of Internal Medicine, Linz General Hospital, Linz, Austria.
rainer.hubmann@akh.linz.at
BACKGROUND AND STUDY AIMS: Acute variceal bleeding is a life-threatening
complication of liver cirrhosis. Essential factors for survival after variceal
bleeding are the rapidity and efficacy of initial primary hemostasis. Endoscopic
and vasoactive therapy is the gold standard in the management of acute variceal
hemorrhage. The primary aim of this study was to evaluate the use of
self-expandable metallic stents to arrest uncontrollable acute variceal
bleeding. PATIENTS AND METHODS: Between November 2002 and May 2005, esophageal
stents were implanted in 20 patients (18 men, two women; mean age 52, range
27-87) with massive ongoing bleeding from esophageal varices, as an alternative
treatment to balloon tamponade. The patients had not been successfully managed
with prior pharmacologic or endoscopic therapy. They had had one to five
previous bleeding episodes (mean 2.4). Eight of the patients were in Child-Pugh
grade B and 12 in grade C. A new type of stent with special introducers was
developed that allowed placement without radiographic assistance. RESULTS: The
stents were successfully placed in all of the patients and were left in place
for 2-14 days. Bleeding from the esophageal varices ceased immediately after
implantation of the stent in all cases. While the stent was in place, further
diagnostic steps were carried out to optimize management of the patients'
illness and portal hypertension. No recurrent bleeding, morbidity, or mortality
occurred during treatment with the esophageal stent. All of the stents were
extracted without any complications after definitive treatment had been started.
CONCLUSIONS: In this pilot study, the new method of implantation of an
esophageal stent was found to be a safe and effective treatment for massive
bleeding from esophageal varices in patients with liver cirrhosis. These initial
clinical results will of course have to be confirmed in comparative studies
including a large number of patients.
Hepatology. 2006 Sep;44(3):640-9.
The effect of single oral low-dose losartan on posture-related
sodium handling in post-TIPS ascites-free cirrhosis.
Therapondos G, Hol L, Benjaminov F, Wong F.
Division of Gastroenterology, Department of Medicine, Toronto General Hospital,
University of Toronto, Canada.
Post-TIPS ascites-free patients with cirrhosis and previous refractory ascites
demonstrate subtle sodium retention when challenged with a high sodium load.
This is also observed in pre-ascitic patients with cirrhosis. This phenomenon is
dependent on an intrarenal angiotensin II (ANG II) mechanism related to the
assumption of erect posture. We investigated whether similar mechanisms were
involved in post-TIPS ascites-free patients, by studying 10 patients with
functioning TIPS and no ascites. We measured the effect of changing from supine
to erect posture on sodium excretion at baseline and after single oral low dose
losartan (7.5 mg) which has been shown to blunt proximal and distal tubular
sodium reabsorption in pre-ascites. At baseline, the assumption of erect posture
produced a reduction in sodium excretion (from 0.30+/-0.06 to 0.13+/-0.02 mmol/min,
P=.05), which was mainly due to an increase in proximal tubular reabsorption of
sodium (PTRNa) (69.7+/-3.1% to 81.1+/-1.8%, P=.003). The administration of
losartan resulted in a blunting of PTRNa (supine 69.7+/-3.1% to 63.9+/-3.9%,
P=.01 and erect 81.1+/-1.8% to 73.8+/-2.4%, P=.01), accompanied by an increased
distal tubular reabsorption of sodium in both postures, with no overall
improvement in sodium excretion on standing. In conclusion, post-TIPS ascites-free
patients with cirrhosis exhibit erect posture-induced sodium retention. We
speculate that (1) this effect is partly mediated by the effect of ANG II on
PTRNa and (2) that the inability of low dose losartan to block the erect
posture-induced sodium retention may be related to the erect posture-induced
rise in aldosterone which is unmodified by losartan.
Can J Gastroenterol. 2006 Aug;20(8):531-4.
Acute management and secondary prophylaxis of esophageal variceal
bleeding: a western Canadian survey.
Cheung J, Wong W, Zandieh I, Leung Y, Lee SS, Ramji A, Yoshida EM.
Department of Medicine, University of Alberta, Edmonton.
BACKGROUND: Acute esophageal variceal bleeding (EVB) is a major cause of
morbidity and mortality in patients with liver cirrhosis. Guidelines have been
published in 1997; however, variability in the acute management and prevention
of EVB rebleeding may occur. METHODS: Gastroenterologists in the provinces of
British Columbia, Alberta, Manitoba and Saskatchewan were sent a self-reporting
questionnaire. RESULTS: The response rate was 70.4% (86 of 122). Intravenous
octreotide was recommended by 93% for EVB patients but the duration was
variable. The preferred timing for endoscopy in suspected acute EVB was within
12 h in 75.6% of respondents and within 24 h in 24.6% of respondents. Most
(52.3%) gastroenterologists do not routinely use antibiotic prophylaxis in acute
EVB patients. The preferred duration of antibiotic therapy was less than three
days (35.7%), three to seven days (44.6%), seven to 10 days (10.7%) and
throughout hospitalization (8.9%). Methods of secondary prophylaxis included
repeat endoscopic therapy (93%) and beta-blocker therapy (84.9%). Most
gastroenterologists (80.2%) routinely attempted to titrate beta-blockers to a
heart rate of 55 beats/min or a 25% reduction from baseline. The most common
form of secondary prophylaxis was a combination of endoscopic and
pharmacological therapy (70.9%). CONCLUSIONS: Variability exists in some areas
of EVB treatment, especially in areas for which evidence was lacking at the time
of the last guideline publication. Gastroenterologists varied in the use of
prophylactic antibiotics for acute EVB. More gastroenterologists used
combination secondary prophylaxis in the form of band ligation eradication and
beta-blocker therapy rather than either treatment alone. Future guidelines may
be needed to address these practice differences.
J Am Coll Surg. 2006 Aug;203(2):145-51. Epub 2006 Jun 22.
Laparoscopic cholecystectomy in cirrhotic patients: the role of
subtotal cholecystectomy and its variants.
Palanivelu C, Rajan PS, Jani K, Shetty AR, Sendhilkumar K, Senthilnathan P,
Parthasarthi R.
Department of GI and Minimal Access Surgery, Gem Hospital, Coimbatore, Tamilnadu,
India.
BACKGROUND: Open cholecystectomy is associated with considerable morbidity and
mortality in cirrhotic patients. Laparoscopic cholecystectomy may offer a better
option because of the magnification available and the availability of newer
instruments like the ultrasonic shears. We present our experience of 265
laparoscopic cholecystectomies and attempt to identify the difficulties
encountered in this group of patients. STUDY DESIGN: Between 1991 and 2005, 265
cirrhotic patients of Child-Pugh Classification A and B, with symptomatic
gallstones, were subjected to laparoscopic cholecystectomy. We describe here our
tailored approach and our techniques of subtotal cholecystectomy. RESULTS:
Features of acute cholecystitis were present in 35.1% of the patients, and 64.9%
presented with chronic cholecystitis. In 81.5% of the patients, the diagnosis of
cirrhosis was established preoperatively. In 8.3% of the patients, a fundus
first method was adopted when the hilum could not be approached despite
additional ports. Modified subtotal cholecystectomy was performed in a total of
206 patients. Mean operative time in the subtotal cholecystectomy group was 72
minutes; in the standard group, it was 41 minutes. There was no mortality. In
15% of patients, postoperative deterioration in liver function occurred.
Worsening of ascites, port site infection, port site bleeding, intraoperative
hemorrhage, bilious drainage, and stone formation in the remnant were the other
complications encountered. CONCLUSIONS: Laparoscopic cholecystectomy is a safe
and effective treatment for calculous cholecystitis in cirrhotic patients.
Appropriate modification of subtotal cholecystectomy should be practiced,
depending on the risk factors present, to avoid complications.
Transplant Proc. 2006 Jul-Aug;38(6):1659-63.
Total parenteral nutrition: challenges and practice in the
cirrhotic patient.
Buchman AL.
Division of Gastroenterology, Intestinal Rehabilitation Center, Feinberg School
of Medicine, Northwestern University, 676 N. St. Clair Street, Chicago,
Illinois, USA. a-buchman@northwestern.edu
Patients with cirrhosis develop metabolic derangements of protein, carbohydrate,
and lipid metabolism. Malnutrition is commonplace and is associated with
morbidity and mortality. Specific nutrient deficiencies may occur and enteral or
parenteral nutritional support may improve outcome in appropriately selected
patients. Parenteral nutrition itself has been associated with hepatic
dysfunction, although the preponderance of evidence suggests that hepatic
dysfunction is more a function of the underlying disorder and malabsorption.
Intravenously infused organic nutrients may be metabolized differently than the
same nutrient consumed enterally. The pathophysiology of total parenteral
nutrition-associated liver disease is discussed as well as potential management
options.
Am J Transplant. 2006 Jun;6(6):1398-406.
No Improvement in Long-Term Liver Transplant Graft Survival in
the Last Decade: An Analysis of the UNOS Data.
Futagawa Y, Terasaki PI, Waki K, Cai J, Gjertson DW.
Terasaki Foundation Laboratory, Los Angeles, California, USA.
We analyzed change in outcomes during two successive 5-year periods (period I =
1992-1996 vs period II = 1997-2002) among 35 186 deceased adult liver transplant
recipients reported to the United Network for Organ Sharing (UNOS) Registry. The
5-year graft survival was 67.4% in the first period and 67.5% in the second,
though the 1-year survival had improved from 81.0 to 83.5%. Comparison of
blended survival rates during the two study periods showed decreased long-term
graft survival in period II, explicable by an increased number of hepatitis C
virus cirrhosis (HCV) patients and an increase in patients with HCV antibodies (HCVab)
during this later period. Analysis wherein these patients with HCV were excluded
revealed the same long-term graft survival during both periods. Non-HCV patients
who had HCVab also had worse 5-year graft survival. We conclude that hepatitis C
prevented improved outcomes during period II and that improved, more effective,
treatment for hepatitis C virus would have great positive impact on overall
survival of liver transplant recipients.
Arch Surg. 2006 Apr;141(4):385-8; discussion 388.
Distal splenorenal shunt: preferred treatment for recurrent
variceal hemorrhage in the patient with well-compensated cirrhosis.
Elwood DR, Pomposelli JJ, Pomfret EA, Lewis WD, Jenkins RL.
Division of Hepatobiliary Surgery and Liver Transplantation, Lahey Clinic
Medical Center, Burlington, Mass.
HYPOTHESIS: Distal splenorenal shunt (DSRS) is a safe and effective treatment
for patients with Child-Pugh class A and B cirrhosis with recurrent variceal
hemorrhage after failed transjugular intrahepatic portosystemic shunt. DESIGN:
Retrospective case review. SETTING: Hepatobiliary surgery and liver
transplantation department in a tertiary referral medical center. PATIENTS:
Between August 1, 1985, and May 1, 2005, 119 patients with Child-Pugh class A
and B cirrhosis underwent DSRS for recurrent variceal hemorrhage. Of these, 17
(14.3%) had thrombosed or failing transjugular intrahepatic portosystemic shunt
prior to DSRS. INTERVENTION: Distal splenorenal shunt for recurrent variceal
hemorrhage after failure of conservative management. MAIN OUTCOME MEASURES:
Morbidity, mortality, and subsequent liver transplantation rate. RESULTS: The
overall perioperative morbidity rate was 31.5%. Thirteen patients (11.7%)
developed encephalopathy and 6 (5.4%) had recurrent variceal hemorrhage. Other
complications included portal vein thrombosis, pancreatitis, pancreatic
pseudocyst, pneumonia, and wound infection. The 30-day operative mortality rate
was 6.4% (n = 7). The 1-year survival rate was 85.9%. The incidence of DSRS for
failed transjugular intrahepatic portosystemic shunt during the first 12 years
of the study (1985-1997) was 11.1% (9/81). This proportion increased to 26.7%
(8/30) during the second half of the study (1997-2005). During the 20-year
period, 15 patients (13.5%) underwent liver transplantation a mean of 5.1 years
after DSRS without an increase in morbidity or mortality after transplantation.
CONCLUSIONS: Distal splenorenal shunt may be the preferred treatment for
recurrent variceal hemorrhage in the patient with well-compensated cirrhosis. In
addition, DSRS does not cause increased morbidity or mortality in subsequent
liver transplantation.
Transpl Infect Dis. 2006 Mar;8(1):3-12.
Rejection rates in a randomised trial of tacrolimus monotherapy
versus triple therapy in liver transplant recipients with hepatitis C virus
cirrhosis.
Samonakis DN, Mela M, Quaglia A, Triantos CK, Thalheimer U, Leandro G, Pesci A,
Raimondo ML, Dhillon AP, Rolles K, Davidson BR, Patch DW, Burroughs AK.
Liver Transplantation and Hepatobiliary Unit, Royal Free Hospital, Hampstead,
London, UK.
Background. Reducing immunosuppression not only reduces complications but also
may lessen recurrent hepatitis C virus (HCV) infection after liver
transplantation. Patients/Methods. HCV-infected cirrhotic patients randomised to
tacrolimus monotherapy (MT) or triple therapy (TT) using tacrolimus 0.1
mg/kg/day, azathioprine 1 mg/kg/day, and prednisolone 20 mg/day, tapering over 3
months. Results. Twenty-seven patients (MT) and 29 (TT) - median follow up 661
days (range, 1-1603). Rejection episodes (protocol/further biopsies) within
first 3 months and use of empirical treatment were evaluated. New rejection was
diagnosed if repeat biopsy (5-day interval) did not show improvement. Treated
rejection episodes: 20 MT (15 biopsy-proven) vs. 24 TT (21 biopsy-proven), with
19 (MT) vs. 24 (TT) methylprednisolone boluses. Overall: 35 episodes (MT) and 46
(TT). Fewer MT patients had histological rejection (70%) than TT patients (86%),
with fewer episodes of rejection (18.5% vs. 10%), and more moderate rejection
(22% vs. 41%). The MT group had higher early tacrolimus levels. Rates of renal
dysfunction, retransplantation, and death were not significantly different.
Conclusion. Tacrolimus monotherapy is a viable immunosuppressive strategy in HCV-infected
liver transplant recipients.
Clin Transplant. 2006 Mar;20(2):211-20.
Long-term follow-up after recurrence of primary biliary cirrhosis
after liver transplantation in 100 patients.
Jacob DA, Neumann UP, Bahra M, Klupp J, Puhl G, Neuhaus R, Langrehr JM.
Department of General, Visceral and Transplantation Surgery, Humboldt University
of Berlin, Charite Virchow Clinic, Berlin, Germany.
Orthotopic liver transplantation (OLT) is the only effective curative therapy
for end-stage primary biliary cirrhosis (PBC). Survival after OLT is excellent,
although recent data have shown a recurrence rate of PBC of up to 32% after
transplantation. The aim of this study is to investigate the course after
disease recurrence, particularly with regard to liver function and survival in a
long-term follow-up. Between April 1989 and April 2003, 1553 liver
transplantations were performed in 1415 patients at the Charite, Virchow Clinic.
Protocol liver biopsies were taken after one, three, five, seven, 10 and 13 yr.
One hundred (7%) patients suffered from histologically proven PBC. Primary
immunosuppression consisted of cyclosporine (n=54) or tacrolimus (Tac) (n=46).
Immediately after OLT, all patients received ursodeoxycholic acid.
Corticosteroids were withdrawn three to six months after OLT. The median age of
the 85 women and 15 men was 55 yr (range 25-66 yr). The median follow-up after
liver transplantation was 118 months (range 16-187 months) and after recurrence
30 months (range 4-79 months). Actuarial patient survival after five, 10 and 15
yr was 87, 84 and 82% respectively. Ten patients (10%) died after a median
survival time of 32 months. Two of these patients developed organ dysfunction
owing to recurrence of PBC. Histological recurrence was found in 14 patients
(14%) after a median time of 61 months (range 36-122 months). Patients with Tac
immunosuppression developed PBC recurrence more often (p<0.05) and also earlier
(p<0.05). Fifty-seven patients developed an acute rejection and two patients a
chronic rejection episode. Liver function did not alter within the first five yr
after histologically proven PBC recurrence. Multivariate analysis of the
investigated patients showed that the recipient's age and Tac immunosuppression
were significant risk factors for PBC recurrence. Long-term follow-up of up to
15 yr after liver transplantation, owing to PBC, in addition to maintenance of
liver function, shows excellent organ and patient survival rates. Although
protocol liver biopsies revealed histological recurrence in 14 (14%) patients,
only two patients developed graft dysfunction. Tac-treated patients showed more
frequently and also earlier histologically proven PBC recurrence; however, in
our population we could not observe an impact on graft dysfunction and patient's
survival.
Gastroenterology. 2006 Mar;130(3):715-20.
Excellent long-term survival in patients with primary biliary
cirrhosis and biochemical response to ursodeoxycholic Acid.
Pares A, Caballeria L, Rodes J.
Liver Unit, Digestive Diseases Institute, Hospital Clinic, IDIBAPS, Barcelona,
Spain. pares@ub.edu
BACKGROUND & AIMS: Because the efficacy of UDCA on long-term outcome of primary
biliary cirrhosis (PBC) has not been completely elucidated, we have assessed the
course and survival of patients with PBC treated with UDCA and compared with the
survival predicted by the Mayo model and the estimated survival of a
standardized population. METHODS: (One hundred ninety-two patients [181 women]
with PBC treated with UDCA [15 mg/kg per day] for 1.5-14 years.) Response to
treatment was defined by an alkaline phosphatase decrease greater than 40% of
baseline values or normal levels after 1 year of treatment. The predicted
survival was obtained by the Mayo model and the estimated survival was taken
from the standardized matched Spanish population. RESULTS: Seventeen patients
died or fulfilled criteria for liver transplantation (8.9%). The observed
survival was higher than that predicted by the Mayo model and lower than that of
the control population (P < .001). One hundred seventeen patients (61%)
responded to treatment. The survival of responders was significantly higher than
that predicted by the Mayo model and similar to that estimated for the control
population (P = .15). By contrast, the survival of patients without biochemical
response was lower than that estimated for the Spanish population (P < .001)
although higher than that predicted by the Mayo model. CONCLUSIONS: Biochemical
response to UDCA after 1 year is associated with a similar survival to the
matched control population, clearly supporting the favorable effects of this
treatment in PBC. The suboptimal survival of nonresponders identifies the group
for further treatments.
Liver Transpl. 2006 Feb;12(2):320-3.
Indications for chronic albumin infusion.
Perkins JD.
Liver Transplantation Worldwide, University of Washington Medical Center,
Seattle, WA.
While transjugular intrahepatic portosystemic shunt (TIPS) is a common therapy
for cirrhotic patients with diuretic-resistant or diuretic-refractory ascites,
some patients are unsuitable for the procedure for technical or medical reasons.
We report our experience with the use of chronic intravenous albumin infusions
to achieve diuresis in this difficult patient population and review the historic
experience of chronic albumin infusions as a treatment for ascites. Nineteen
patients with cirrhosis and diuretic-resistant or diuretic-refractory ascites
who were deemed unsuitable for TIPS received outpatient intravenous albumin
infusions (50 g) weekly for at least 4 weeks. The following endpoints were
retrospectively recorded: serum sodium, serum creatinine, blood urea nitrogen,
hematocrit, bilirubin, albumin, international normalized ratio, body weight, and
Model for End-stage Liver Disease (MELD) score. The contraindications for TIPS
included the following: portal vein thrombosis, two; advanced age, one;
encephalopathy, nine; hyperbilirubinemia, five; and other, two. Compared to
pretreatment, posttreatment weight decreased in 17 patients, remained unchanged
in 0 patients, and increased in 2 patients. The overall mean change in body
weight (before vs. after therapy) was 8 lb (P < 0.05). The only significant
change in biochemistries was an increase in serum albumin from 2.5 g/dl before
therapy to 3.5 g/dl after therapy (P < 0.05). We conclude that (1) recurrent
intravenous weekly albumin infusions resulted in significant loss of edema and
ascites as measured by loss of body weight, and (2) clinicians may want to
consider chronic albumin infusions for selected patients with refractory ascites
who are not candidates for TIPS.
J Hepatol. 2006 Feb;44(2):400-6. Epub 2005 Nov 15.
Long term outcome and response to therapy of primary biliary
cirrhosis-autoimmune hepatitis overlap syndrome.
Chazouilleres O, Wendum D, Serfaty L, Rosmorduc O, Poupon R.
Service d'Hepatologie, Centre de reference des maladies inflammatoires du foie
et des voies biliaires, Hopital Saint Antoine, Assistance Publique-Hopitaux de
Paris, Faculte de Medecine Pierre et Marie Curie, Paris, France.
BACKGROUND/AIMS: Whether primary biliary cirrhosis (PBC)-autoimmune hepatitis (AIH)
overlap syndrome requires immunosuppressive therapy in addition to
ursodeoxycholic acid (UDCA) is a controversial issue. METHODS: Seventeen
patients with simultaneous form of strictly defined overlap were followed for
7.5 years. First-line treatment was UDCA alone (UDCA) in 11 and combination of
immunosuppressors and UDCA (UDCA+IS) in 6. RESULTS: Characteristics at
presentation were not significantly different between the 2 groups. In the
UDCA+IS group (f-up 7.3 years), biochemical response in terms of AIH features
(ALT<2ULN and IgG<16g/L) was achieved in 4/6 and fibrosis did not progress. In
the UDCA group, biochemical response was observed in three patients together
with stable or decreased fibrosis (f-up 4.5 years) whereas the eight others were
non-responders with increased fibrosis in four (f-up 1.6 years). Seven of these
eight patients subsequently received combined therapy for 3 years. Biochemical
response was obtained in 6/7 and no further increase of fibrosis was
demonstrated. Overall, fibrosis progression in non-cirrhotic patients occurred
more frequently under UDCA monotherapy (4/8) than under combined therapy (0/6)
(P=0.04). CONCLUSIONS: Combination of UDCA and immunosuppressors appears to be
the best therapeutic option for strictly defined PBC-AIH overlap syndrome.
J Gastroenterol Hepatol. 2006 Jan;21(1):303-7.
Terlipressin versus albumin in paracentesis-induced circulatory
dysfunction in cirrhosis: A randomized study.
Singh V, Kumar R, Nain CK, Singh B, Sharma AK.
Department of Hepatology, Postgraduate Institute of Medical Education and
Research, Chandigarh, India.
Background: Therapeutic paracentesis in patients with cirrhosis induces arterial
vasodilatation, causes a decrease in effective arterial blood volume and leads
to circulatory dysfunction, which can be prevented by intravenous albumin.
However, the use of albumin, being a blood product, is controversial. Recently,
terlipressin, a vasoconstrictor, has been successfully used to combat this
adverse effect of therapeutic paracentesis. Therefore, the aim of the present
study was to investigate the preventive effect of terlipressin on paracentesis-induced
circulatory dysfunction in patients with cirrhosis after therapeutic
paracentesis and compared with that of intravenous albumin. Methods: Forty
patients with cirrhosis and tense ascites underwent therapeutic paracentesis
with albumin or terlipressin in a randomized pilot study at a tertiary center.
Effective arterial blood volume was assessed by measuring plasma renin activity
at baseline and at 4-6 days after treatment. Results: Effective arterial blood
volumes as indicated by plasma renin activity before and 4-6 days after
paracentesis did not differ in the two groups (19.15 +/- 12.1 to 20.33 +/- 12.8
ng/mL per h, P = 0.46 in the albumin group; and 20.11 +/- 10.6 to 21.08 +/-
10.52 ng/mL per h, P = 0.44 in the terlipressin group). Plasma aldosterone
concentrations before and 4-6 days after paracentesis were also similar in both
groups (1334.75 +/- 1058 to 1440.0 +/- 1161 pg/mL, P = 0.06 in the albumin
group; and 1473.0 +/- 1168 to 1572.29 +/- 1182 pg/mL, P = 0.24 in the
terlipressin group). Both terlipressin and albumin prevented paracentesis-induced
renal impairment in these patients. Conclusions: Terlipressin may be as
effective as intravenous albumin in preventing paracentesis-induced circulatory
dysfunction in patients with cirrhosis after therapeutic paracentesis.
Hepatology. 2006 Jan 30;43(S1):S99-S112 [Epub ahead of print]
Nonalcoholic fatty liver disease: From steatosis to cirrhosis.
Farrell GC, Larter CZ.
The Storr Liver Unit, Westmead's Millennium Institute, University of Sydney at
Westmead Hospital, Westmead, NSW, Australia.
Nonalcoholic steatohepatitis (NASH), the lynchpin between steatosis and
cirrhosis in the spectrum of nonalcoholic fatty liver disorders (NAFLD), was
barely recognized in 1981. NAFLD is now present in 17% to 33% of Americans, has
a worldwide distribution, and parallels the frequency of central adiposity,
obesity, insulin resistance, metabolic syndrome and type 2 diabetes. NASH could
be present in one third of NAFLD cases. Age, activity of steatohepatitis, and
established fibrosis predispose to cirrhosis, which has a 7- to 10-year
liver-related mortality of 12% to 25%. Many cases of cryptogenic cirrhosis are
likely endstage NASH. While endstage NAFLD currently accounts for 4% to 10% of
liver transplants, this may soon rise. Pathogenic concepts for NAFLD/NASH must
account for the strong links with overnutrition and underactivity, insulin
resistance, and genetic factors. Lipotoxicity, oxidative stress, cytokines, and
other proinflammatory mediators may each play a role in transition of steatosis
to NASH. The present "gold standard" management of NASH is modest weight
reduction, particularly correction of central obesity achieved by combining
dietary measures with increased physical activity. Whether achieved by
"lifestyle adjustment" or anti-obesity surgery, this improves insulin resistance
and reverses steatosis, hepatocellular injury, inflammation, and fibrosis. The
same potential for "unwinding" fibrotic NASH is indicated by studies of the
peroxisome proliferation activator receptor (PPAR)-gamma agonist "glitazones,"
but these agents may improve liver disease at the expense of worsening obesity.
Future challenges are to approach NAFLD as a preventive public health initiative
and to motivate affected persons to adopt a healthier lifestyle. (Hepatology
2006;43:S99-S112.).
Wien Klin Wochenschr. 2005 Dec;117 Suppl 6:54-9.
[Peritoneal dialysis in patients with liver cirrhosis and/or
ascites.]
[Article in German]
Paul G.
3. Medizinische Abteilung, Donauspital, Sozialmedizinisches Zentrum Ost der
Stadt Wien, Wien, Austria, gernot.paul@wienkav.at.
In older textbooks the use of peritoneal dialysis (PD) in patients with liver
cirrhosis and/or ascites was contraindicated. Only a small number of papers have
focused on this problem and they mainly consist of case reports and
retrospective studies of small numbers of patients. In addition, most
nephrologists' experience of performing PD in patients with liver diseases is
rather limited. Nevertheless, for these patients PD offers a wide range of
advantages, such as a simplified ascites management, since repeated abdominal
punctures become unnecessary. Furthermore, because of continuous peritoneal
ultrafiltration, hemodynamic tolerance during PD is significantly better than in
hemodialysis and results in a markedly lower frequency of hypotensive episodes.
The risk of nosocomial infection with hepatitis B or C viruses can also be
reduced by treating these patients with home PD. Although some authors suggest
that PD patients with liver cirrhosis have an especially increased risk of
Gram-negative peritonitis, currently available data show controversial results.
There is also little information in the literature on the impact of increased
peritoneal protein loss on malnutrition and outcome of these patients.
Nevertheless, recent studies have shown that protein loss into the peritoneal
cavity in PD patients with liver cirrhosis is high only initially, stabilizing
at a lower level in the further course of treatment. In conclusion, in patients
with end-stage renal disease suffering from liver cirrhosis and/or ascites, PD
can be considered as a good or adequate treatment option.
Am Surg. 2005 Dec;71(12):996-1000.
Cirrhosis and trauma: a deadly duo.
Christmas AB, Wilson AK, Franklin GA, Miller FB, Richardson JD, Rodriguez JL.
Department of Surgery, University of Louisville, Louisville, Kentucky 40292,
USA.
It has been previously reported that trauma patients with cirrhosis undergoing
emergency abdominal operations exhibit a fourfold increase in mortality
independent of their Child's classification. We undertook this review to assess
the impact of cirrhosis on trauma patients. We reviewed the records of patients
from 1993 to 2003 with documented hepatic cirrhosis and compared them to a 2:1
control population without hepatic cirrhosis and matched for age, sex, Injury
Severity Score (ISS), and Glasgow Coma Score (GCS). Demographic, severity of
injury, and outcome data were recorded. Student's t test and X2 were used for
statistical analysis and a P < 0.05 was significant. Sixty-one patients had
documented cirrhosis and were compared to 156 matched controls. Comparing the
two groups demonstrates there was no difference in age, ISS, or GCS. Intensive
care stay, hospital length of stay, blood requirements in the first 24 hours
postinjury, and mortality (33% vs 1%) was significantly greater in the trauma
patients with cirrhosis. Fifty-five per cent of deaths in the cirrhosis group
was due to sepsis, and, as the Child's class increases, so does the mortality
(Child's A, 15%; B, 37%; and C, 63%). In 64 per cent of cirrhotics without an
emergent abdominal operation, mortality was 21 per cent. In the 36 per cent of
cirrhotics who had emergent abdominal operation, mortality was 55 per cent.
Hepatic cirrhosis in trauma patients, regardless of severity of injury or the
need for an abdominal intervention, is a poor prognostic indicator. The
necessity of an abdominal operative intervention further amplifies this effect.
Trauma and cirrhosis is, in fact, a deadly duo.
Arq Gastroenterol. 2005 Oct-Dec;42(4):256-62. Epub 2006 Jan 19.
Trimethoprim-sulfamethoxazole versus norfloxacin in the
prophylaxis of spontaneous bacterial peritonitis in cirrhosis.
Alvarez RF, Mattos AA, Correa EB, Cotrim HP, Nascimento TV.
Department of Gastroenterology and Hepatology, Federal School of Medical
Sciences of Porto Alegre, Porto Alegre, RS, Brazil.
BACKGROUND: The prognosis of patients with chronic liver disease and spontaneous
bacterial peritonitis is poor, being of great importance its prevention. AIM: To
compare the effectiveness of trimethoprim-sulfamethoxazole versus norfloxacin
for prevention of spontaneous bacterial peritonitis in patients with cirrhosis
and ascites. PATIENTS AND METHODS: Fifty seven patients with cirrhosis and
ascites were evaluated between March 1999 and March 2001. All of them had a
previous episode of spontaneous bacterial peritonitis or had ascitic fluid
protein concentration < or = 1 g/dL and/or serum bilirubin > or = 2.5 mg/dL. The
patients were randomly assigned to receive either 800/160 mg/day of
trimethoprim-sulfamethoxazole 5 days a week or 400 mg of norfloxacin daily. The
mean time of observation was 163 days for the norfloxacin group and 182 days for
the trimethoprim-sulfamethoxazole group. In the statistical analysis,
differences were considered significant at the level of 0.05. RESULTS: According
to the inclusion criteria, 32 patients (56%) were treated with norfloxacin and
25 (44%) with trimethoprim-sulfamethoxazole. Spontaneous bacterial peritonitis
occurred in three patients receiving norfloxacin (9.4%) and in four patients
receiving trimethoprim-sulfamethoxazole (16.0%). Extraperitoneal infections
occurred in 10 patients receiving norfloxacin (31.3%) and in 6 patients
receiving trimethoprim-sulfamethoxazole (24.0%). Death occurred in seven
patients (21.9%) who received norfloxacin and in five (20.0%) who received
trimethoprim-sulfamethoxazole. Side effects occurred only in the
trimethoprim-sulfamethoxazole group. CONCLUSION: In spite of the reduced number
of patients and time of observation, trimethoprim-sulfamethoxazole and
norfloxacin were equally effective in spontaneous bacterial peritonitis
prophylaxis, suggesting that trimethoprim-sulfamethoxazole is a valid
alternative to norfloxacin.
Radiologe. 2005 Nov;45(11):1012-9.
[Interventions for benign biliary strictures.]
[Article in German]
Lubienski A, Duex M, Lubienski K, Blietz J, Kauffmann GW, Helmberger T.
Institut fur Radiologie, Campus Lubeck des Universitatsklinikums
Schleswig-Holstein.
Due to their potential for serious consequences, even including biliary liver
cirrhosis, benign biliary strictures pose a considerable diagnostic and
therapeutic challenge. In addition to inflammatory disease or an acute liver
injury, iatrogenically caused biliary strictures following hepatobiliary surgery
represent in 95% of cases the main cause for all benign entities.The diagnosis
should be determined noninvasively with magnetic resonance
cholangiopancreaticography (MRCP). Invasive techniques such as ERCP or
percutaneous transhepatic cholangiography (PTC) should be reserved for unclear
cases and first performed before the scheduled intervention.Depending on the
site and cause of the stricture, surgical and interventional procedures are
employed in the treatment of biliary strictures. The best results are obtained
in short-segment strictures of the main bile duct. Interventional methods such
as balloon dilation and/or stent application with concomitant drain insertion
achieve patency rates of up to 75% after 5 and 55% after 12 years with a total
complication rate of 5-8%. Due to the fact that most of the cases involve
cicatricial fibroses, predisposition for recurrence of biliary strictures after
interventional therapy can be very high, ranging up to 66% depending on the
localization.
Hepatology. 2005 Nov;42(5):1184-93.
Methotrexate (MTX) plus ursodeoxycholic acid (UDCA) in the
treatment of primary biliary cirrhosis.
Combes B, Emerson SS, Flye NL, Munoz SJ, Luketic VA, Mayo MJ, McCashland TM,
Zetterman RK, Peters MG, Di Bisceglie AM, Benner KG, Kowdley KV, Carithers RL Jr,
Rosoff L Jr, Garcia-Tsao G, Boyer JL, Boyer TD, Martinez EJ, Bass NM, Lake JR,
Barnes DS, Bonacini M, Lindsay KL, Mills AS, Markin RS, Rubin R, West AB,
Wheeler DE, Contos MJ, Hofmann AF.
The University of Texas Southwestern Medical Center at Dallas, Dallas, TX.
This placebo-controlled, randomized, multicenter trial compared the effects of
MTX plus UDCA to UDCA alone on the course of primary biliary cirrhosis (PBC).
Two hundred and sixty five AMA positive patients without ascites, variceal
bleeding, or encephalopathy; a serum bilirubin less than 3 mg/dL; serum albumin
3 g/dL or greater, who had taken UDCA 15 mg/kg daily for at least 6 months, were
stratified by Ludwig's histological staging and then randomized to MTX 15
mg/m(2) body surface area (maximum dose 20 mg) once a week while continuing on
UDCA. The median time from randomization to closure of the study was 7.6 years
(range: 4.6-8.8 years). Treatment failure was defined as death without liver
transplantation; transplantation; variceal bleeding; development of ascites,
encephalopathy, or varices; a doubling of serum bilirubin to 2.5 mg/dL or
greater; a fall in serum albumin to 2.5 g/dL or less; histological progression
by at least two stages or to cirrhosis. Patients were continued on treatment
despite failure of treatment, unless transplantation ensued, drug toxicity
necessitated withdrawal, or the patient developed a cancer. There were no
significant differences in these parameters nor to the time of development of
treatment failures observed for patients taking UDCA plus MTX, or UDCA plus
placebo. The trial was conducted with a stopping rule, and was stopped early by
the National Institutes of Health at the advice of our Data Safety Monitoring
Board for reasons of futility. In conclusion, methotrexate when added to UDCA
for a median period of 7.6 years had no effect on the course of PBC treated with
UDCA alone. Supplementary material for this article can be found on the
HEPATOLOGY website (http://www.interscience.wiley.com/jpages/0270-9139/suppmat/index.html).
(HEPATOLOGY 2005;42:1184-1193.).
Liver Transpl. 2005 Oct;11(10):1252-7.
Recurrent primary biliary cirrhosis: Peritransplant factors and
ursodeoxycholic acid treatment post-liver transplant.
Guy JE, Qian P, Lowell JA, Peters MG.
Department of Medicine University of California San Francisco, CA.
Primary biliary cirrhosis (PBC) recurs after orthotopic liver transplantation (OLT)
in up to one-third of patients. These patients are typically asymptomatic, can
be identified by abnormal liver biochemistries, and have evidence of histologic
recurrence on liver biopsy. The effect of treatment on recurrence has not been
determined. This pilot study evaluates the factors associated with recurrent PBC
and describes our experience using ursodeoxycholic acid treatment in this
patient population. Forty-eight patients with PBC were followed for at least 1
yr post-OLT, and 27 patients (56%) developed abnormal serum alkaline phosphatase.
Seventeen patients (35%) had evidence of recurrent PBC by liver biopsy. Patients
with recurrent PBC had a trend toward longer warm ischemia times and more
episodes of acute cellular rejection in the first year posttransplant, but this
was not significant in multivariate analysis. Donor or recipient age, donor and
recipient cytomegalovirus status, and dose of immunosuppression did not
correlate with recurrence of PBC. Those patients diagnosed with recurrent PBC
were placed on ursodeoxycholic acid, 15 mg/kg daily, with improvement in serum
alkaline phosphatase in the majority. In conclusion, recurrent PBC is not
infrequent post-OLT, and ursodeoxycholic acid can be used with some benefit
post-OLT. Treatment effects on long-term survival are not known. (Liver Transpl
2005;11:1252-1257.).
Rev Prat. 2005 Sep 30;55(14):1539-48.
[Liver cirrhosis in adults: etiology and specific treatments]
[Article in French]
Fartoux L, Serfaty L.
Service d'hepatologie, hopital Saint-Antoine, 75571 Paris. laetitia.fartoux@sat.ap-hop.paris.fr
Cirrhosis is the result of chronic inflammation and of the progressive increase
of fibrosis. In France, hepatitis C infection is the second cause of cirrhosis
after alcohol abuse. The other causes of cirrhosis are: hepatitis B infection,
genetic haemochromatosis, autoimmune hepatitis, primary biliary cirrhosis,
drug-induced cirrhosis, secondary biliary cirrhosis, Wilson's disease and al-antitrypsin
deficiency. Etiological treatment is based upon: abstinence in case of alcoholic
cirrhosis, the combination of pegylated interferon alpha (PEG IFN) with
ribavirin in case of C viral cirrhosis, the PEG IFN and the nucleoside analogs
in case of B viral cause; corticosteroids and immunosuppressive drugs in case of
autoimmune cirrhosis; venesections in case of genetic haemochromatosis and
stopping the drug in case of drug-induced cirrhosis. The complications of
cirrhosis such as ascites, oesophageal varices, bleeding, hepatic encephalopathy
and hepatocellular carcinoma mainly explain the high rate of morbidity and
mortality. Liver transplantation is the established therapy for decompensated
liver disease of any etiology significantly changed the outcome of patients with
advanced cirrhosis.
Z Gastroenterol. 2005 Sep;43(9):1051-9.
Ursodeoxycholic acid in the therapy for primary biliary
cirrhosis: effects on progression and prognosis.
Leuschner U, Manns MP, Eisebitt R.
Medizinische Klinik der Johann Wolfgang Goethe Universitat, Frankfurt am Main,
Germany. U.Leuschner@em.uni-Frankfurt.de
The effects in clinical studies of UDCA on the endpoints "death" or
"pre-transplantation survival" can only be shown when UDCA therapy is started in
an early disease phase, preferably in stage I but no later than stage II, and is
then continued into stages III/IV, or preferably stage IV. The reasons for this
lie in the observation that, in stages I/II, no patient suffers from progressive
disease that irrevocably leads to death or transplantation, while a measurable
effect of UDCA, as is true for other drugs and other hepatic diseases, continues
to dwindle and finally disappears as patients progress through the fibrotic and
cirrhotic stages III and IV. Hence, administration of UDCA must begin in the
phase of progressive inflammation (stages I and II) and the outcome documented
after many years of long-term therapy. This requires very large, probably
unattainable, patient collectives. Whether it is justified to administer placebo
to one-half of these patients over such an extended period of time represents a
profound ethical dilemma. Because these arguments were not considered in the two
meta-analyses cited above or in any other study, they do not allow a definitive
statement on the life expectancy of patients on UDCA therapy. On the other hand,
it is possible using generally accepted, independent prognostic variables and
mathematical models, whose limitations are well-known and must be considered, to
predict with a high degree of accuracy the disease course of treated and
untreated patients and calculate their life expectancy and/or
pre-transplantation survival. Because UDCA exerts a significant positive effect
on the most important prognostic markers for PBC, such as serum bilirubin,
piecemeal necroses, histological disease progression, ascites and edema, and
apparently the scores for pruritus and fatigue, this permits us to demonstrate
not only a decrease in the incidence of transplantation but also to calculate a
prolongation in life expectancy.
Semin Liver Dis. 2005 Aug;25(3):321-6.
The natural history of PBC: has it changed?
Lee YM, Kaplan MM.
Tufts-New England Medical Center, Boston, MA 02111, USA. ylee@tufts-nemc.org
The prognosis and natural history of primary biliary cirrhosis (PBC) have
improved significantly during the last few decades. Patients are diagnosed at
earlier stages, are more likely to be asymptomatic at diagnosis, and are more
likely to receive medical treatment. The survival of asymptomatic patients is
longer than the median survival of symptomatic patients. The natural history of
PBC has been assessed in the presence of effective therapy, ursodeoxycholic acid
(UDCA). Evidence suggests that UDCA delays histological progression in PBC and
decreases the risk of development of esophageal varices. Survival of UDCA-treated
patients is better than that of untreated patients and also is better than that
predicted by the Mayo model. For patients in early stages of PBC, UDCA treatment
may normalize survival. However, patients with stage III and IV PBC do not
respond as well to UDCA. Therefore, there is a continued need for additional
treatment in patients with advanced disease.
Semin Liver Dis. 2005 Aug;25(3):311-20.
Overlap syndromes.
Beuers U, Rust C.
Department of Medicine II-Grosshadern, Ludwig Maximilians-University of Munich,
Germany. Beuers@med.uni-muenchen.de
In hepatology, the term overlap syndrome describes variant forms of the major
hepatobiliary autoimmune diseases, autoimmune hepatitis (AIH), primary biliary
cirrhosis (PBC), and primary sclerosing cholangitis (PSC). Patients with overlap
syndromes present with both hepatitic and cholestatic biochemical and
histological features of AIH, PBC, and/or PSC, and usually show a progressive
course toward liver cirrhosis and liver failure without adequate treatment.
AIH-PBC overlap syndromes have been reported in almost 10% of adults with AIH or
PBC, whereas AIH-PSC overlap syndromes were found in 6 to 8% of children,
adolescents, and young adults with AIH or PSC. A minority of patients may also
show transition from stable PBC to AIH, AIH to PBC, or AIH to PSC, as documented
by single case reports and small case series. Single cases of AIH and autoimmune
cholangitis (antimitochondrial antibody-negative PBC) overlap have also been
reported. Empiric medical treatment of AIH-PBC and AIH-PSC overlap syndromes
includes anticholestatic therapy with ursodeoxycholic acid and immunosuppressive
therapy with corticosteroids and azathioprine. In end-stage disease, liver
transplantation is the treatment of choice.
Am J Gastroenterol. 2005 Aug;100(8):1876-85.
Colchicine for primary biliary cirrhosis: a cochrane
hepato-biliary group systematic review of randomized clinical trials.
Gong Y, Gluud C.
The Cochrane Hepato-Biliary Group, Copenhagen Trial Unit, Center for Clinical
Intervention Research, H:S Rigshospitalet, Copenhagen University Hospital,
Copenhagen, Denmark.
OBJECTIVES: Colchicine is used for patients with primary biliary cirrhosis due
to its immunomodulatory and antifibrotic potential. The results from randomized
clinical trials have, however, been inconsistent. We conducted a systematical
review to evaluate the effect of colchicine for primary biliary cirrhosis.
METHODS: We identified randomized clinical trials comparing colchicine with
placebo/no intervention. We analyzed effects by fixed and random effects model.
We investigated heterogeneity by subgroup and sensitivity analyses. RESULTS: We
included 10 trials involving 631 patients, four of which were high-quality
trials. No significant differences were detected between colchicine and
placebo/no intervention regarding mortality (relative risk (RR), 1.21; 95%
confidence interval (CI), 0.71-2.06), mortality or liver transplantation (RR =
1.00; 95% CI, 0.67-1.49), liver complications, liver biochemical variables,
liver histology, or adverse events. Regarding mortality, an extreme case
analysis favoring colchicine did not demonstrate beneficial effects of
colchicine, whereas an extreme case analysis favoring placebo/no intervention
demonstrated a detrimental effect of colchicine (RR = 2.28; 95% CI, 1.17-4.44).
The number of patients without improvement of pruritus significantly decreased
in the colchicine group (RR = 0.75; 95% CI, 0.65-0.87). However, this estimate
was based on only 156 patients from three trials. CONCLUSIONS: There is
insufficient evidence to support the use of colchicine for patients with primary
biliary cirrhosis. As we are unable to exclude a risk of increased mortality, we
recommend to use colchicine only in randomized clinical trials. (Am J
Gastroenterol 2005;100:1-10).
Hepatogastroenterology. 2005 Jul-Aug;52(64):1180-5.
Clinical outcome of 214 liver resections using microwave tissue
coagulation.
Satoi S, Kamiyama Y, Matsui Y, Kitade H, Kaibori M, Yamamoto H, Yanagimoto H,
Takai S, Kwon AH.
Department of Surgery, Kansai Medical University, Osaka, Japan. satoi@takii.kmu.ac.jp
BACKGROUND/AIMS: Liver resection is the most effective form of treatment for
patients with hepatocellular carcinoma. The use of a microwave tissue coagulator
has been reported to enable limited liver resections for the patients with poor
hepatic reserve. Herein, we report the clinical outcome of 214 patients with HCC
who underwent non-anatomical liver resection using MTC in accordance with the
tumor size. METHODOLOGY: A consecutive series of 214 patients who underwent
liver resections using MTC were observed over a 10-year study period. The
clinical characteristics of patients were evaluated. The operative mortality and
morbidity, overall patient survival and disease-free survival were calculated.
RESULTS: Seventy-two percent of patients suffered from type C hepatitis and 47%
of patients had pathologically proven liver cirrhosis. The overall patient
survival rates were 91, 72, and 58% at 1, 3 and 5 years, respectively.
Disease-free survival rates were 74, 46, and 28% at 1, 3 and 5 years,
respectively. Postoperative morbidity was 36% and hospital mortality was 2.8%.
Complications in most patients were well controlled. CONCLUSIONS: Non-anatomical
liver resections using MTC, in accordance with tumor sizes, can be achieved
safely with acceptable results and without the need to use special techniques.
Cochrane Database Syst Rev. 2005 Jul 20;(3):CD004385.
Methotrexate for primary biliary cirrhosis.
Gong Y, Gluud C.
Copenhagen Trial Unit, Centre for Clinical Intervention Research, Copenhagen
University Hospital, Dept. 7102, Blegdamsvej 9, H:S Rigshospitalet, Copenhagen,
DENMARK, DK-2100.
BACKGROUND: Methotrexate, a folic acid antagonist with immunosuppressive
properties, has been used to treat patients with primary biliary cirrhosis. The
therapeutic responses to methotrexate in randomised clinical trials have been
heterogeneous. OBJECTIVES: To assess the beneficial and harmful effects of
methotrexate for patients with primary biliary cirrhosis. SEARCH STRATEGY:
Relevant randomised clinical trials were identified by searching The Cochrane
Hepato-Biliary Group Controlled Trials Register (June 2004), The Cochrane
Central Register of Controlled Trials on The Cochrane Library (Issue 2, 2004),
MEDLINE (January 1966 to August 2004), EMBASE (January 1980 to August 2004), and
manual searches of bibliographies. We contacted authors of trials and
pharmaceutical companies. SELECTION CRITERIA: Randomised clinical trials
comparing methotrexate with placebo, no intervention, or another drug were
included irrespective of blinding, language, year of publication, and
publication status. DATA COLLECTION AND ANALYSIS: Our primary outcomes were
mortality and mortality or liver transplantation. Dichotomous outcomes were
reported as relative risk (RR) and hazard ratio (HR) if applicable. Continuous
outcomes were reported as weighted mean difference (WMD). We examined
intervention effects by using both a random-effects model and a fixed-effect
model. Heterogeneity was investigated by subgroup analyses and sensitivity
analyses. MAIN RESULTS: We identified four trials (370 patients) that compared
methotrexate with placebo with or without ursodeoxycholic acid as
co-intervention. One additional trial (87 patients) compared methotrexate with
colchicine without and later with ursodeoxycholic acid as co-intervention. The
methodological quality of the trials was low. We did not find significant
effects of methotrexate on pruritus, fatigue, liver complications, liver
biochemistry, liver histology, or adverse events. The pruritus score (WMD -
0.68, 95% CI - 1.11 to - 0.25), the levels of serum alkaline phosphatases (WMD -
0.41, 95% CI - 0.70 to - 0.12) and plasma immunoglobulin M (WMD - 0.47, 95% CI -
0.74 to - 0.20) were significantly lower in the patients receiving methotrexate.
AUTHORS' CONCLUSIONS: Methotrexate increased mortality in patients with primary
biliary cirrhosis. We do not recommend methotrexate for patients with primary
biliary cirrhosis outside randomised trials.
Cochrane Database Syst Rev. 2005 Jul 20;(3):CD004792.
Vitamin K for upper gastrointestinal bleeding in patients with
liver diseases.
Marti-Carvajal A, Marti-Pena A.
BACKGROUND: Upper gastrointestinal bleeding is one of the most frequent causes
of morbidity and mortality in the course of liver cirrhosis. Several treatments
are used for upper gastrointestinal bleeding in patients with liver diseases.
However, supplementary interventions are often used as well. One of them is
vitamin K administration, but it is unknown whether it benefits or harms
patients with liver disease and upper gastrointestinal bleeding. OBJECTIVES: To
assess the beneficial and harmful effects of vitamin K for patients with liver
disease and upper gastrointestinal bleeding. SEARCH STRATEGY: We searched The
Cochrane Hepato-Biliary Group Controlled Trials Register (February 2004), which
comprises references identified from comprehensive electronic database searches
and handsearching of relevant journals and abstract books of conference
proceedings, The Cochrane Central Register of Controlled Trials (CENTRAL) in The
Cochrane Library (Issue 1, 2004), MEDLINE (1966 to March 2004), EMBASE (1988 to
March 2004), and LILACS (1982 to March 2004). Additional randomised trials were
sought from the reference lists of the trials found and reviews identified by
the electronic searches. SELECTION CRITERIA: We intended to include randomised
clinical trials. DATA COLLECTION AND ANALYSIS: We intended to summarise data by
standard Cochrane Collaboration methodologies. MAIN RESULTS: We could not find
any randomised trials on vitamin K for upper gastrointestinal bleeding in
patients with liver diseases. AUTHORS' CONCLUSIONS: We were unable to identify
randomised trials on the safety and efficacy of vitamin K for upper
gastrointestinal bleeding in patients with liver diseases. The effects of
vitamin K need to be tested in randomised clinical trials.
Arch Surg. 2005 Jul;140(7):650-4; discussion 655.
The safety of intra-abdominal surgery in patients with cirrhosis:
model for end-stage liver disease score is superior to Child-Turcotte-Pugh
classification in predicting outcome.
Befeler AS, Palmer DE, Hoffman M, Longo W, Solomon H, Di Bisceglie AM.
Division of Gastroenterology and Hepatology, Department of Internal Medicine,
Saint Louis University, St Louis, MO 63110, USA.
HYPOTHESIS: We hypothesized that the model for end-stage liver disease (MELD)
score may be a better and less subjective method than the Child-Turcotte-Pugh
score for stratifying patients with cirrhosis before abdominal surgery. DESIGN:
Retrospective medical record review. SETTING: Tertiary care institution.
PATIENTS: Fifty-three adult patients with histologically proven cirrhosis
undergoing abdominal surgery at Saint Louis University Hospital, St Louis, Mo,
between 1991 and 2001. Those undergoing hepatic surgery (such as resection or
transplantation) or closed abdominal surgery (such as hernia repair) were
excluded. MAIN OUTCOME MEASURE: A poor outcome after surgery was defined as
death or liver transplantation within 90 days of the operative procedure or a
hospital stay of longer than 21 days. Demographic, clinical, and laboratory
features predictive of poor outcome were assessed by multivariate analysis.
RESULTS: A total of 13 patients (25%) had poor outcomes including 9 deaths
(17%). Model for end-stage liver disease score and plasma hemoglobin levels
lower than 10 g/dL were found to be independent predictors of poor outcomes. A
MELD score of 14 or greater was a better clinical predictor of poor outcome than
Child-Turcotte-Pugh class C. CONCLUSIONS: A MELD score of 14 or greater should
be considered as a replacement for Child-Turcotte-Pugh class C as a predictor of
being very high risk for abdominal surgery. Patients with cirrhosis with
hemoglobin levels lower than 10 g/dL should receive corrective blood
transfusions before abdominal surgery.
Hepatology. 2005 Jun;41(6):1305-12.
A randomized, controlled crossover trial of ondansetron in
patients with primary biliary cirrhosis and fatigue.
Theal JJ, Toosi MN, Girlan L, Heslegrave RJ, Huet PM, Burak KW, Swain M,
Tomlinson GA, Heathcote EJ.
Department of Medicine, University Health Network, University of Toronto,
Toronto, Canada.
Fatigue is common in primary biliary cirrhosis (PBC). Altered central
serotonergic neurotransmission may be involved in its pathogenesis. This
multicenter, randomized, double-blind, placebo-controlled, crossover trial
evaluated the efficacy of ondansetron, a selective 5-HT3 receptor subtype
antagonist, for treating fatigue in PBC. A crossover design was chosen, allowing
subjects to serve as their own controls-appropriate to evaluate fatigue, a
subjective symptom. Sixty patients with clinically stable PBC, a Fatigue
Severity Score (FSS) > 4, and no other identifiable cause for fatigue were
enrolled. Subjects were randomized to receive ondansetron (4 mg) or placebo
orally 3 times daily for 4 weeks (period 1). Subjects then crossed over, after a
minimum 1-week washout period, for a further 4 weeks of ondansetron or placebo
(period 2). Fatigue was measured at the beginning and end of each period by
using the FSS and Fatigue Impact Scale (FIS). Six patients withdrew; the
remaining 54 subjects had a mean baseline FSS of 5.55 (+/-0.1). Response to
study medication in period 1 versus period 2 was not uniform; thus, it was
necessary to analyze the trial periods separately. In period 1, there was no
significant additional fatigue reduction on ondansetron over placebo. During
period 2, FSS and FIS decreased significantly on ondansetron versus placebo (P =
.001). However, period 2 results were invalidated because drug side effects
unblinded subjects (constipation affected 63.0% of patients taking ondansetron,
versus 13.3% on placebo). In conclusion, ondansetron administration did not
confer clinically significant fatigue reduction when compared with placebo in
our study population.Dig Liver Dis. 2005 Mar;37(3):176-180. Epub 2004 Dec 15.
-
Quantitative treatment of the hyponatremia of cirrhosis.
Castello L, Pirisi M, Sainaghi PP, Bartoli E.
Department of Internal Medicine, Piemonte Orientale Hospital, 'Amedeo Avogadro',
Via Solaroli, 17, 28100 Novara, Italy.
BACKGROUND.: Hyponatremia represents a frequent complication of liver cirrhosis,
associated with adverse events and death. It is caused either by excessive water
retention or solute depletion, or a combination of both. AIMS.: To determine the
cause of hyponatremia clinically and to examine the usefulness of quantitative
calculations of water excess and Na deficit to guide treatment. METHODS.: We
studied 23 patients with liver cirrhosis and PNa</=131meq/L to determine the
cause of hyponatremia and results of quantitative treatment. RESULTS.: The most
frequent cause of hyponatremia was diuretic-induced Na depletion, which occurred
in 14 out of 23 instances, while four patients had water excess. Hyponatremia
was corrected after a quantitative estimate of the Na deficit or relative water
excess by algebraic formulas. The former was quantitatively replenished as 3%
NaCl, the latter was excreted with the technique of furosemide-induced diuresis
and re-infusion of solute, but not water, losses. After quantitative
replacement, there was a significant correlation (R=0.98, P<0.001) between the
Na concentration predicted mathematically and that actually measured.
CONCLUSIONS.: The hyponatremia of cirrhosis is frequently caused by diuretics.
Its treatment can be effectively guided with the aid of quantitative estimates
of Na deficit and/or water excess in all instances, although the methods of
correction described are indicated in severe clinical conditions.
Clin Rev Allergy Immunol. 2005 Apr;28(2):167-74.
Surgical treatment of primary biliary cirrhosis and primary
sclerosing cholangitis.
Loehe F, Schauer RJ.
Department of Surgery, Ludwig-Maximilians-University of Munich, Klinikum
Grosshadern, Munich, Germany.
Primary biliary cirrhosis (PBC) and primary sclerosing cholangitis (PSC) are
progressivecholestatic liver diseases of supposed auto-immune etiology. The
clinical course is unpredictableand, in many patients, leads to end-stage liver
disease or a poor quality of life. Conservativetherapy only has a limited effect
on the natural history, but orthotopic liver transplantation(OLT) offers a
definitive therapeutic option.Retrospective analysis was performed for 38
patients with PBC and 17 patients with PSCwho underwent OLT between January 1986
and June 2003 at our institution. Median followupafter OLT was 72 mo.Cumulative
survival at 5 yr post-OLT was 84% in the PBC group and 73% in the PSCgroup.
Compared with OLT for other benign diseases, actuarial survival rates at 5 and
10 yrpost-OLT were significantly better for patients with PBC, whereas there was
no difference insurvival after OLT for patients with PSC. Survival rate at 5 yr
post-OLT was significantlyincreased for patients with PBC who had a Child-Pugh B
liver cirrhosis (93%) compared withthose who had Child-Pugh C cirrhosis (60%).
Retransplantation rate was 18.2% (resulting frombiliary complications in three
cases). Surgical techniques had no effect on outcome after OLTin both groups.We
concluded that liver transplantation represents a safe and beneficial therapy
forpatients with end-stage PBC. Cirrhotic patients with PSC also benefit from
OLT, with an outcomecomparable to that of liver cirrhosis of other etiologies.
Cochrane Database Syst Rev. 2005 Apr 18;(2):CD002148.
Colchicine for alcoholic and non-alcoholic liver fibrosis and
cirrhosis.
Rambaldi A, Gluud C.
Copenhagen Trial Unit, Centre for Clinical Intervention Research, Department
7102, H:S Rigshospitalet,, Copenhagen University Hospital, Blegdamsvej 9,
Copenhagen, DENMARK, DK-2100.
BACKGROUND: Alcohol and hepatotropic viruses cause the majority of liver
cirrhosis cases in the Western World. Colchicine is an anti-inflammatory and
anti-fibrotic medication. Several randomised clinical trials have addressed the
question whether colchicine has any efficacy in patients with alcoholic or
non-alcoholic fibrosis and cirrhosis. OBJECTIVES: To assess the beneficial and
harmful effects of colchicine in patients with alcoholic or non-alcoholic
fibrosis or cirrhosis, excluding primary biliary cirrhosis. SEARCH STRATEGY: The
Cochrane Hepato-Biliary Group Controlled Trials Register, The Cochrane
Controlled Trials Register on The Cochrane Library, MEDLINE, EMBASE, Web of
Science, and full text searches were combined (September 2004). Manufacturers
and researchers in the field were also contacted. SELECTION CRITERIA: We
included randomised trials irrespective of blinding, language, or publication
status comparing per oral colchicine with placebo or no intervention for
patients with fibrosis or cirrhosis induced by either alcohol, virus, or unknown
factors (cryptogenic). DATA COLLECTION AND ANALYSIS: The statistical package (RevMan
Analyses) provided by The Cochrane Collaboration was used. The methodological
quality of the randomised clinical trials was evaluated. MAIN RESULTS: We could
include fifteen randomised clinical trials in which 1714 patients were
randomised. We found no significant effects of colchicine on mortality (relative
risks (RR) 1.00, 95% confidence interval (CI) 0.87 to 1.16), liver-related
mortality (RR 1.08, 95% CI 0.88 to 1.33), complications (RR 1.01, 95% CI 0.74 to
1.38), liver biochemistry, liver histology, and alcohol consumption (RR 1.03,
95% CI 0.77 to 1.39). Colchicine was associated with a significantly increased
risk of adverse events (RR 4.35, 95% CI 2.16 to 8.77). AUTHORS' CONCLUSIONS:
Colchicine should not be used for alcoholic, viral, or cryptogenic liver
fibrosis or liver cirrhosis outside randomised clinical trials.
Gastroenterology. 2005 Apr;128(4):882-90.
Colchicine treatment of alcoholic cirrhosis: a randomized,
placebo-controlled clinical trial of patient survival.
Morgan TR, Weiss DG, Nemchausky B, Schiff ER, Anand B, Simon F, Kidao J, Cecil
B, Mendenhall CL, Nelson D, Lieber C, Pedrosa M, Jeffers L, Bloor J, Lumeng L,
Marsano L, McClain C, Mishra G, Myers B, Leo M, Ponomarenko Y, Taylor D, Chedid
A, French S, Kanel G, Murray N, Pinto P, Fong TL, Sather MR.
VA Long Beach Healthcare Systems, Long Beach, CA 90822, USA. timothy.morgan@med.va.gov
BACKGROUND & AIMS: Colchicine improved survival and reversed cirrhosis in
several small clinical trials. We compared the efficacy and safety of long-term
colchicine, as compared with placebo, in patients with advanced alcoholic
cirrhosis. METHODS: Five hundred forty-nine patients with advanced (Pugh B or C)
alcoholic cirrhosis were randomized to receive either colchicine 0.6 mg twice
per day (n = 274) or placebo (n = 275). Treatment lasted from 2 to 6 years. The
primary outcome was all-cause mortality. Secondary outcomes were liver-related
morbidity and mortality. Liver biopsy was requested prior to entry and after 24
months of treatment. RESULTS: Attendance at scheduled clinic visits and
adherence with study medication were similar in colchicine and placebo groups.
Alcohol intake was less than 1 drink per day in 69% of patients. In an
intention-to-treat analysis, all-cause mortality was similar in colchicine (49%)
and placebo (45%) patients (P = .371). Mortality attributed to liver disease was
32% in colchicine and 28% in placebo patients (P = .337). Fewer patients
receiving colchicine developed hepatorenal syndrome. In 54 patients with repeat
liver biopsies after 24 or more months of treatment, cirrhosis improved to
septal fibrosis in 7 patients (3 colchicine, 4 placebo) and to portal fibrosis
in 1 patient (colchicine). CONCLUSIONS: In patients with advanced alcoholic
cirrhosis, colchicine does not reduce overall or liver-specific mortality. Liver
histology improves to septal fibrosis in a minority of patients after 24 months
of treatment, with similar rates of improvement in patients receiving placebo
and colchicine. Colchicine is not recommended for patients with advanced
alcoholic cirrhosis.
Gastroenterology. 2005 Apr;128(4):870-81.
Randomized study comparing banding and propranolol to prevent
initial variceal hemorrhage in cirrhotics with high-risk
esophageal varices.
Jutabha R, Jensen DM, Martin P, Savides T, Han SH, Gornbein J.
Division of Digestive Diseases, David Geffen School of Medicine at UCLA, Los
Angeles, CA, USA.
BACKGROUND & AIMS: Standard care for prevention of first esophageal variceal
hemorrhage is beta-blockade, but this may be ineffective or unsafe. Our purpose
was to compare endoscopic banding with propranolol for prevention of first
variceal hemorrhage. METHODS: In a multicenter, prospective trial, 62 patients
with cirrhosis with high-risk esophageal varices were randomized to propranolol
(titrated to reducing resting pulse by > or =25%) or banding (performed monthly
until varices were eradicated) and were followed up on the same schedule for a
mean duration of 15 months. The primary end point was treatment failure, defined
as the development of endoscopically documented variceal hemorrhage or a severe
medical complication requiring discontinuation of therapy. Direct costs were
estimated from Medicare reimbursements and fixed or variable charges for
services up to treatment failure. RESULTS: Background variables of the treatment
groups were similar. The trial was stopped early after an interim analysis
showed that the failure rate of propranolol was significantly higher than that
of banding (6/31 vs. 0/31; difference, 19.4%; P = .0098; 95% confidence interval
for true difference, 6.4%-37.2%). Significantly more propranolol than banding
patients had esophageal variceal hemorrhage (4/31 vs. 0/31; difference, 12.9%; P
= .0443; 95% confidence interval for true difference, 0.8%-29%), and the
cumulative mortality rate was significantly higher in the propranolol than in
the banding group (4/31 vs. 0/31; difference, 12.9%; P = .0443; 95% confidence
interval for true difference, 0.8%-29%). Direct costs of care were not
significantly different. CONCLUSIONS: For patients with cirrhosis with high-risk
esophageal varices and no history of variceal hemorrhage, propranolol-treated
patients had significantly higher failure rates of failure, first esophageal
varix hemorrhage, and cumulative mortality than banding patients. Direct costs
of medical care were not significantly different.
Rev Med Suisse. 2005 Jan 19;1(3):242, 245-7.
[Auto-immune liver diseases and their treatment]
[Article in French]
Hess J, Thorens J, Pache I, Troillet FX, Moradpour D, Gonvers JJ.
Service de gastro-enterologie et d'hepatologie, CHUV, Rue du Bugnon 44, 1011
Lausanne. jurghess@bluewin.ch
There are three main types of auto-immune liver disease, auto-immune hepatitis,
primary biliary cirrhosis and primary sclerosing cholangitis. In the case of
auto-immune hepatitis, prednisone therapy, with or without azathioprine, can
improve quality of life and halt progression to cirrhosis. If there is no
response or if the therapy is poorly tolerated, mycophenolate mofetil or
cyclosporin should be considered. Ursodeoxycholic acid (UDCA), at a dosage of 13
to 15 mg/kg/day slows the progression of fibrosis in patients with primary
biliary cirrhosis. Pruritis may be treated with cholestyramine, rifampicin or
opiate antagonists. Ursodeoxycholic acid at a dosage of 20 to 30 mg/kg/day will
slow the evolution of fibrosis.
Rev Med Suisse. 2005 Jan 19;1(3):249-50, 252-5.
[Complications of liver cirrhosis: oesophageal varices, ascites
and hepato-cellular carcinoma]
[Article in French]
Troillet FX, Halkic N, Froehlich F, Moradpour D, Gonvers JJ, Denys A.
Service de chirurgie viscerale, CHUV, Lausanne. Francois-Xavier.Troillet@chuv.hospvd.ch
The principal treatment for bleeding oesophageal varices is endoscopic ligation.
Non-cardioselective beta-blockers are the gold-standard of primary prophylaxis.
The principal treatment for ascites is a salt-free diet and diuretics, mainly
spironolactone, if necessary associated with a loop diuretic. In refractory
ascites, paracentesis or installation of a transjugular intrahepatic
portosystemic shunt (TIPS) are two possible treatment options. Cirrhosis
patients are at higher risk of developing hepato-cellular carcinoma. Surgery is
only possible in a small number of cases. Percutaneous destruction techniques
have nearly the same survival rate as that obtained by surgery and should be
proposed to patients where surgery is not an option.
Liver Int. 2005 Feb;25(1):117-21.
Raloxifene improves bone mass in osteopenic women with primary
biliary cirrhosis: results of a pilot study.
Levy C, Harnois DM, Angulo P, Jorgensen R, Lindor KD.
Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN, USA.
Levy C, Harnois DM, Angulo P, Jorgensen R, Lindor KD. Raloxifene improves bone
mass in osteopenic women with primary biliary cirrhosis - results of a pilot
study. Liver International 2005: 25: 117-121. (c) Blackwell Munksgaard 2005
Abstract: Background/Aims: Bone disease is common in patients with primary
biliary cirrhosis (PBC). Our aim was to evaluate safety and efficacy of
raloxifene in this population. Methods: Nine postmenopausal women with PBC were
enrolled and seven completed the study. Subjects received raloxifene 60 mg daily
for 1 year. Each patient on raloxifene was age-matched to three controls. Liver
biochemistries were monitored periodically; bone mineral density (BMD) of the
lumbar spine (LS) and femoral neck (FN) was measured at baseline and at 1 year.
Results: No significant adverse effects were reported. Liver biochemistries
remained unchanged. Baseline LS-BMD was similar in the treatment group and
controls [median 0.720 g/cm(2) (range 0.620-0.867) vs. 0.740 g/cm(2)
(0.570-1.040), P=0.5]. Conclusion: Compared with baseline, LS-BMD improved
significantly with 1 year of therapy [0.72 g/cm(2) (0.62-0.87) vs. 0.74 g/cm(2)
(0.63-0.97), P=0.02]. FN-BMD remained stable [0.53 g/cm(2) (0.50-0.60) vs. 0.54
g/cm(2) (0.49-0.63), P=0.6]. Improvement in LS BMD was seen in patients on
raloxifene but not in matched controls [0.02 g/cm(2) (0.01-0.10) vs. 0.00
g/cm(2) (-0.120-0.040), P=0.06)]. In conclusion, raloxifene appears safe and of
benefit in preventing bone loss in patients with PBC. Larger studies with longer
follow-up are warranted.
Aliment Pharmacol Ther. 2005 Feb 1;21(3):217-26.
Long-term ursodeoxycholic acid therapy for primary biliary
cirrhosis: a follow-up to 12 years.
Chan CW, Gunsar F, Feudjo M, Rigamonti C, Vlachogiannakos J, Carpenter JR,
Burroughs AK.
Liver Transplantation and Hepatobiliary Medicine, Royal Free Hospital, London,
UK.
Summary Background : It is uncertain whether ursodeoxycholic acid therapy slows
down the progression of primary biliary cirrhosis, according to two
meta-analyses. However, the randomized trials evaluated had only a median of 24
months of follow-up. Aim : To evaluate long-term ursodeoxycholic acid therapy in
primary biliary cirrhosis. Methods : We evaluated 209 consecutive primary
biliary cirrhosis patients, 69 compliant with ursodeoxycholic acid and 140
untreated [mean follow-up 5.79 (s.d. = 4.73) and 4.87 (s.d. = 5.21) years,
respectively] with onset of all complications documented. Comparison was made
following adjustment for baseline differences according to Cox modelling, Mayo
and Royal Free prognostic models. Results : Bilirubin and alkaline phosphatase
concentrations improved with ursodeoxycholic acid (at 36 months, P = 0.007 and
0.018, respectively). Unadjusted Kaplan-Meier analysis showed benefit (P =
0.028), as 44 (31%) untreated and 15 (22%) ursodeoxycholic acid patients died or
had liver transplantation. However, there was no difference when adjusted by Cox
modelling (P = 0.267), Mayo (P = 0.698) and Royal Free models (P = 0.559). New
pruritus or fatigue or other complications were not different, either before or
after adjustment for baseline characteristics. Conclusions : Long-term
ursodeoxycholic acid therapy did not alter disease progression in primary
biliary cirrhosis patients despite a significant improvement in serum bilirubin
and alkaline phosphatase consistent with, and similar to, those seen in
ursodeoxycholic acid cohorts in randomized trials.
Gastroenterology. 2005 Feb;128(2):297-303.
The effect of ursodeoxycholic acid therapy on the natural course
of primary biliary cirrhosis.
Corpechot C, Carrat F, Bahr A, Chretien Y, Poupon RE, Poupon R.
Background & Aims: We used a multistate modeling approach to assess the effect
of ursodeoxycholic acid (UDCA) therapy on the natural course of primary biliary
cirrhosis (PBC), which remains controversial. Methods: Our population included
262 patients with PBC who had received 13-15 mg/kg UDCA daily for a mean of 8
years (range, 1-22 years). Data were analyzed using a multistate Markov model,
with histologic stage progression, death, and orthotopic liver transplantation (OLT)
as main end points. Survival without OLT was compared with that predicted by the
updated Mayo model and with the expected survival in the control population.
Results: Forty-five patients developed cirrhosis, 20 underwent OLT, and 16 died
by the censor date. Ten deaths were due to liver disease. The overall survival
rates were 92% at 10 years and 82% at 20 years. Survival rates without OLT were
84% and 66% at 10 and 20 years, respectively, which were slightly lower than the
survival rate of an age- and sex-matched control population (relative risk [RR],
1.4; P = .1) but better than the spontaneous survival rate as predicted by the
updated Mayo model (RR, .5; P < .01). The survival rate of patients in stage 1
and 2 was similar to that in the control population (RR, .8; P = .5), whereas
the probability of death or OLT remained significantly increased in treated
patients in late histologic stages (RR, 2.2; P < .05). Conclusions: Treatment
with UDCA alone normalizes the survival rate of patients with PBC when given at
early stages. However, there is a continued need for new therapeutic options in
patients with advanced disease.
Am J Gastroenterol. 2004 Dec;99(12):2348-55.
Pilot studies of single and combination antiretroviral therapy in
patients with primary biliary cirrhosis.
Mason AL, Farr GH, Xu L, Hubscher SG, Neuberger JM.
Section of Gastroenterology and Hepatology, Ochsner Clinic Foundation, New
Orleans, Louisiana, USA.
OBJECTIVE: Preliminary reports suggest that patients with primary biliary
cirrhosis (PBC) have evidence of human betaretrovirus infection. The aim of this
study was to determine whether antiviral therapy impacts on the disease process.
METHODS: We conducted two consecutive open-labeled, nonrandomized, 1-yr pilot
studies; the first with lamivudine 150 mg/day and the second with Combivir
combination therapy using lamivudine 150 mg and zidovudine 300 mg twice a day.
Eleven PBC patients enrolled in each study, seven patients were entered into
both studies, and one patient was withdrawn from each study due to side effects.
RESULTS: Evaluation of liver biopsies before and after lamivudine therapy showed
a 4-5 increase in necroinflammatory score, a 1-1.5 elevation in bile duct
injury, with little change in the percentage of portal tracts with bile ducts
(50-52%). None of the patients in the lamivudine study normalized alkaline
phosphatase. Histological assessment following Combivir therapy revealed a 6 to
4 improvement in necroinflammatory score (p < 0.03, 95% CI: 0.53-2.33), a 3 to 1
reduction in bile duct injury (p < 0.02, 95% CI: 1.08-2.07), and a 45-75%
increase in portal tracts with bile ducts (p < 0.05, 95% CI: 0.02-0.29). In the
Combivir cohort, five patients normalized alkaline phosphatase and four
developed normal AST, ALT, and alkaline phosphatase. CONCLUSIONS: Histological
and biochemical endpoints were achieved in the Combivir pilot study suggesting a
larger placebo-controlled trial is required as a proof of principle to assess
whether antiviral therapy impacts the PBC disease process.
Hepatol Res. 2004 Dec;30S:25-29. Epub 2004 Nov 11.
Branched-chain amino acid treatment in patients with liver
cirrhosis.
Suzuki K, Kato A, Iwai M.
First Department of Internal Medicine, Iwate Medical University, 19-1 Uchimaru,
Morioka 020-8505, Japan.
We discuss branched-chain amino acid (BCAA) treatment for the management of
hepatic encephalopathy (HE) and protein-energy malnutrition (PEM) in patients
with liver cirrhosis (LC). PEM is closely associated with the prognosis of
patients with LC independently of liver function. Therefore, adequate protein
and energy intake is a fundamental management to improve the status of PEM in
patients with LC. However, it is difficult to maintain good nutritional status
with diet therapy alone in patients with LC, because the majority of these
patients have disturbances of the nutritious metabolism including urea synthesis
in the liver, together with the existence of portal-systemic shunt which is
related with the pathogenesis of HE. BCAA enriched amino acid solution was
administered at first to treat chronic HE based on amino acid imbalance and
neurotransmitter theory. Furthermore, recent studies have suggested that the
supplement of BCAA enriched oral mixture and BCAA granules with diet therapy
might improve the status of PEM in patients with LC. However, as the effects of
these BCAA supplements are basically related to the severity of liver damage,
further investigations are required to identify the efficacy of these
treatments.
Rev Gastroenterol Disord. 2004 Fall;4(4):175-85.
Management of ascites in patients with end-stage liver disease.
Saadeh S, Davis GL.
Division of Hepatology, Baylor University Medical Center, Dallas, Texas, USA.
Ascites is the most common complication in patients with decompensated
cirrhosis. Approximately 50% of patients with compensated cirrhosis will develop
ascites over a 10-year period. This occurrence is an important milestone in the
natural history of end-stage liver disease because only 50% of patients survive
2 to 5 years (depending on the cause of cirrhosis) after its onset. Salt
restriction and diuretics are the mainstays of therapy, and these measures are
effective in approximately 90% of patients. Large-volume paracentesis or
transjugular intrahepatic portosystemic shunt can be used in patients with
refractory ascites as either a bridge to transplant or as palliation. Cirrhotic
patients with ascites should be carefully monitored for the development of
bacterial peritonitis, and those at greatest risk should receive antibiotic
prophylaxis. When spontaneous bacterial peritonitis is suspected, prompt
diagnostic paracentesis followed by broad-spectrum antibiotics and albumin
infusion can be life saving. Orthotopic liver transplantation should be
considered in all patients with decompensated liver disease with or without
ascites.
Med Hypotheses. 2005;64(1):118-119.
Bupropion for fatigue and as a tumor necrosis factor-alpha
lowering agent in primary biliary cirrhosis.
Altschuler EL, Kast RE.
Mount Sinai School of Medicine, 1425 Madison Avenue, Box 1240, New York, NY
10029, USA.
Primary biliary cirrhosis (PBC) is a chronic cholestatic disease which can often
be severe, progressive and necessitate liver transplantation. The cause of PBC
is not known, and treatments other than liver transplantation are often not
effective. Among the more common and troublesome symptoms of PBC is fatigue. The
etiology of fatigue in PBC is not well-understood, and there is no known
treatment for it. Here, we suggest that for a number of reasons that the safe
and commonly used oral antidepressant bupropion might be effective for fatigue
in PBC: (1) increased monoaminergic and dopaminergic tone to combat fatigue, (2)
treatment of concomitant depression, (3) in general for PBC as a tumor necrosis
factor-alpha (TNF) lowering agent, if TNF is eventually found to play a role in
PBC pathogenesis.
Yakugaku Zasshi. 2004 Nov;124(11):711-24.
Wilson's Disease and Its Pharmacological Treatment.
Hayashi H, Suzuki R, Wakusawa S.
Department of Medicine, Faculty of Pharmaceutical Sciences of Hokuriku
University.
Wilson's disease is an inherited copper toxicosis caused by defective putative
copper transporting ATPase in the liver. Because of impaired biliary secretion,
copper remains in the liver, resulting in chronic hepatic lesions including
fatty metamorphosis, chronic hepatitis and cirrhosis. In the latter stage,
extrapyramidal syndromes may develop with and without symptomatic hepatic
lesions. Acute liver damage associated with hemolysis and deep jaundice may be
the first manifestation. The majority of patients show hypoceruloplasminemia,
which has been used as a screening test for the disease. A large number of
mutations in the ATP7B gene have been reported. Thus, genetic diagnosis might be
limitedly used to presymptomatic diagnosis of siblings when mutations are
identified in an index patient. Introduction of penicillamine caused a
revolution in the treatment of patients. Another chelater, trientine, is now
available for those intolerant of penicillamine. Tetrathiomolibdate and zinc
acetate are additional alternatives currently being tested.
Hypoceruloplasminemia and further reduction after chelation therapy may be
associated with iron overload. This complication is closely related with
impaired transport of ferrous ion due to ferroxidase deficiency. Noncompliance
and teratogenicity are other major concerns because any treatment with the
agents listed above is a life long regimen. Despite various side effects of
penicillamine, its teratogenicity is negligible. These data indicate that
penicillamine is the first choice of drug for this disease.
Cochrane Database Syst Rev. 2004 Oct 18(4):CD004789.
D-penicillamine for primary biliary cirrhosis.
Gong Y, Frederiksen S, Gluud C.
Copenhagen Trial Unit, Centre for Clinical Intervention Research, Copenhagen
University Hospital, Dept. 7102, Blegdamsvej 9, H:S Rigshospitalet, Copenhagen,
DENMARK, DK-2100.
BACKGROUND: D-penicillamine is used for patients with primary biliary cirrhosis
due to its hepatic copper decreasing and immunomodulatory potentials. The
results from randomised clinical trials have been inconsistent. OBJECTIVES: To
systematically review the beneficial and harmful effects of D-penicillamine for
patients with primary biliary cirrhosis. SEARCH STRATEGY: We identified trials
through electronic searches of The Cochrane Hepato-Biliary Group Controlled
Trials Register (September 2003), The Cochrane Central Register of Controlled
Trials on The Cochrane Library (Issue 3, 2003), MEDLINE (January 1966 to
September 2003), EMBASE (January 1980 to September 2003), The Chinese Biomedical
CD Database (January 1979 to August 2003), and LILACS (1982 to 2003); through
manual searches of bibliographies; and by contacting authors of the trials and
pharmaceutical companies. SELECTION CRITERIA: We included randomised clinical
trials comparing D-penicillamine with placebo/no intervention or other control
intervention irrespective of language, year of publication, and publication
status. DATA COLLECTION AND ANALYSIS: Two reviewers independently assessed the
methodological quality of the trials and extracted data, validated by a third
reviewer. The primary outcomes were 1) mortality and 2) a combination of those
who died or underwent liver transplantation. We analysed dichotomous outcomes as
relative risk (RR) with 95% confidence interval (CI) by a fixed effect model and
a random effects model. We investigated sources of heterogeneity by subgroup
analyses and tested the robustness of our findings by sensitivity analyses. MAIN
RESULTS: We included seven trials randomising 706 patients with primary biliary
cirrhosis. D-penicillamine compared with placebo/no intervention tended to
increase mortality (RR 1.34, 95% CI 1.09 to 1.64, fixed; RR 1.46, 95% CI 0.85 to
2.50, random). However, there was substantial heterogeneity. No significant
differences were detected regarding the risks of mortality or liver
transplantation, pruritus, liver complications, progression of liver
histological stage, or the levels of liver biochemical variables (except alanine
aminotransferase). D-penicillamine versus placebo/no intervention significantly
increased the risk of adverse events (RR 3.11, 95% CI 2.33 to 4.16, fixed; RR
4.18, 95% CI 1.38 to 12.69, random). REVIEWERS' CONCLUSIONS: D-penicillamine did
not appear to reduce the risk of mortality, but significantly increased the
occurrences of adverse events in patients with primary biliary cirrhosis. We do
not support the use of D-penicillamine for patients with primary biliary
cirrhosis.
Nippon Geka Gakkai Zasshi. 2004 Oct;105(10):669-73.
[Hepatic failure after liver resection in patients with
cirrhosis]
[Article in Japanese]
Kubo S, Tanaka H, Shuto T, Takemura S, Uenishi T, Tanaka S, Hirohashi K.
Department of Gastroenterological and Hepato-Biliary-Pancreatic Surgery, Osaka
City University Graduate School of Medicine, Osaka, Japan.
Despite improvements in the preoperative assessment of liver function and
advances in surgical techniques, liver resection for hepatocellular carcinoma
still holds a risk for postoperative hepatic failure, especially in patients
with cirrhosis. Physiologic characteristics in patients with cirrhosis include
hyperdynamic state of the systemic circulation, decrease in hepatic blood flow,
portal hypertension, metabolic disorders, dysfunction of the reticuloendothelial
system, and thrombocytopenia. Surgical stress including massive bleeding,
disturbance of hepatic circulation, and infection are risk factors for
postoperative hepatic failure. The risk of hepatic failure also correlates with
the severity of active hepatitis and the degree of hepatic fibrosis. To prevent
postoperative hepatic failure, dopamine, prostaglandin, and hydrocortisone have
been used. Although various treatments including plasma exchange have been tried
in hepatic failure, the results have often been unsatisfactory. Careful
preoperative evaluation of the hepatic functional reserve and the severity of
active hepatitis, and adequate selection of surgical method are important to
prevent postoperative hepatic failure.
Gastroenterology. 2004 Oct;127(4):1123-30.
Recombinant factor VIIa for upper gastrointestinal bleeding in
patients with cirrhosis: a randomized, double-blind trial.
Bosch J, Thabut D, Bendtsen F, D'Amico G, Albillos A, Gonzalez Abraldes J,
Fabricius S, Erhardtsen E, de Franchis R; European Study Group on rFVIIa in UGI
Haemorrhage.
Hospital Clinic, Liver Unit, Barcelona, Spain. jbosch@medicina.ub.es
BACKGROUND & AIMS: Upper gastrointestinal bleeding (UGIB) is a severe and
frequent complication of cirrhosis. Recombinant coagulation factor VIIa (rFVIIa)
has been shown to correct the prolonged prothrombin time in patients with
cirrhosis and UGIB. This trial aimed to determine efficacy and safety of rFVIIa
in cirrhotic patients with variceal and nonvariceal UGIB. METHODS: A total of
245 cirrhotic patients (Child-Pugh < 13; Child-Pugh A = 20%, B = 52%, C = 28%)
with UGIB (variceal = 66%, nonvariceal = 29%, bleeding source unknown = 5%) were
randomized equally to receive 8 doses of 100 microg/kg rFVIIa or placebo in
addition to pharmacologic and endoscopic treatment. The primary end point was a
composite including: (1) failure to control UGIB within 24 hours after first
dose, or (2) failure to prevent rebleeding between 24 hours and day 5, or (3)
death within 5 days. RESULTS: Baseline characteristics were similar between
rFVIIa and placebo groups. rFVIIa showed no advantage over standard treatment in
the whole trial population. Exploratory analyses, however, showed that rFVIIa
significantly decreased the number of failures on the composite end point (P =
0.03) and the 24-hour bleeding control end point (P = 0.01) in the subgroup of
Child-Pugh B and C variceal bleeders. There were no significant differences
between rFVIIa and placebo groups in mortality (5- or 42-day) or incidence of
adverse events including thromboembolic events. CONCLUSIONS: Although no overall
effect of rFVIIa was observed, exploratory analyses in Child-Pugh B and C
cirrhotic patients indicated that administration of rFVIIa significantly
decreased the proportion of patients who failed to control variceal bleeding.
Dosing with rFVIIa appeared safe. Further studies are needed to verify these
findings.
Annu Rev Pharmacol Toxicol. 2004 Oct 07 [Epub ahead of print]
Hepatic Fibrosis: Molecular Mechanisms and Drug Targets.
Lotersztajn S, Julien B, Teixeira-Clerc F, Grenard P, Mallat A.
Unite INSERM 581 Hopital Henri Mondor, 94010 Creteil, France sophie.lotersztajn@im3.inserm.fr,
Unite INSERM 581 Hopital Henri Mondor, 94010 Creteil, France boris.julien@im3.inserm.fr,
Unite INSERM 581 Hopital Henri Mondor, 94010 Creteil, France fatima.clerc@im3.inserm.fr,
Unite INSERM 581 Hopital Henri Mondor, 94010 Creteil, France pascale.grenard@im3.inserm.fr,
Unite INSERM 581 et Service d'Hepatologie et de Gastroenterologie, Hopital Henri
Mondor, 94010 Creteil, ariane.mallat@hmn.ap-hop-paris.fr.
Liver fibrosis is the common response to chronic liver injury, ultimately
leading to cirrhosis and its complications, portal hypertension, liver failure,
and hepatocellular carcinoma. Efficient and well-tolerated antifibrotic drugs
are currently lacking, and current treatment of hepatic fibrosis is limited to
withdrawal of the noxious agent. Efforts over the past decade have mainly
focused on fibrogenic cells generating the scarring response, although promising
data on inhibition of parenchymal injury and/or reduction of liver inflammation
have also been obtained. A large number of approaches have been validated in
culture studies and in animal models, and several clinical trials are underway
or anticipated for a growing number of molecules. This review highlights recent
advances in the molecular mechanisms of liver fibrosis and discusses
mechanistically based strategies that have recently emerged. Expected online
publication date for the Annual Review of Pharmacology and Toxicology Volume 45
is January 6, 2005. Please see http://www.annualreviews.org/catalog/pub_dates.asp
for revised estimates.
Expert Opin Ther Targets. 2004 Oct;8(5):423-35.
Targeted treatments for cirrhosis.
Fallowfield JA, Iredale JP.
Liver Research Group, Division of Infection, Inflammation and Repair,
Southampton General Hospital, Mailpoint 811, D Level, Southampton, SO16 6YD, UK.
jonfalluk@yahoo.co.uk
The causes of hepatic scarring (fibrosis) are protean but, unchecked, all result
in a common fate--the development of cirrhosis--with gross disruption of the
normal liver architecture. Subsequent liver cell dysfunction and portal
hypertension give rise to major systemic complications and premature death.
Cirrhosis and its sequelae represent a huge, and global, healthcare burden. The
success of liver transplantation and the development of efficacious antiviral
regimens for hepatitis B and C should not be underestimated, but they also serve
to highlight our current inability to manipulate the underlying fibrotic process
in many patients with liver disease. Moreover, transplantation as a treatment is
limited by organ availability, among other factors. The development of
antifibrotic therapies is urgently needed and for this we require a mechanistic
and evidence-based approach. Accumulating data from clinical and laboratory
studies demonstrate that even advanced fibrosis and cirrhosis are potentially
reversible. The hepatic stellate cells have been identified as the pivotal
effector cells orchestrating the fibrotic process and, furthermore,
reversibility appears to hinge upon their elimination. This review draws on
recent scientific advances, and highlights emerging therapeutic interventions in
liver fibrosis.
Surgery. 2004 Oct;136(4):804-11.
An initial experience and evolution of laparoscopic hepatic
resectional surgery.
Buell JF, Thomas MJ, Doty TC, Gersin KS, Merchen TD, Gupta M, Rudich SM, Woodle
ES.
Division of Transplantation, University of Cincinnati, OH 45267-0558, USA.
BACKGROUND: The use of minimally invasive procedures has revolutionized modern
surgery. Only recently has laparoscopy been introduced for use in hepatic
surgery. METHODS: Patient demographics, tumor characteristics, and outcomes were
evaluated for all initial cases of laparoscopic hepatic resection. RESULTS:
Twenty-one resections were performed in 17 patients; 5 were performed for
malignancy, of which 3 had underlying cirrhosis, and the remaining 12 for benign
symptomatic disease. Mean patient age was 55.4 (range, 24-82 years). The mean
number of lesions was 1.4 (range, 1-5), having an average size of 7.6 cm (range,
2-30 cm). Mean operative time was 2.8 hours (range, 2-5 hours) hours. Most
resections involved 1 or more Couinaud segments. Mean blood loss was 288 cc
(range, 50-150 cc). Complications included re-operation for hemorrhage (n=2),
biliary leakage (n=1), and death from hepatic failure (n=1). Mean length of stay
was 2.9 days (range, 1-14). When compared with our series of 100 patients who
underwent open hepatic resection for benign tumors, significantly greater means
( P <.05) were noted for blood loss (485 cc), operative time (4.5 hours), and
length of stay (6.5 days). CONCLUSIONS: Laparoscopic hepatic surgery, though
complex, can be performed safely and efficaciously. Minimally invasive surgery
appears to provide several distinct advantages over traditional open hepatic
surgery. However, techniques for the laparoscopic control of bleeding and bile
leak remain in their infancy.
J Hepatol. 2004 Oct;41(4):560-6.
Bleeding ectopic varices-treatment with transjugular intrahepatic
porto-systemic shunt (TIPS) and embolisation.
Vangeli M, Patch D, Terreni N, Tibballs J, Watkinson A, Davies N, Burroughs AK.
Liver Transplantation and Hepatobiliary Unit, Royal Free Hospital and NHS
Hampstead Trust, London, UK.
BACKGROUND/AIMS: Bleeding ectopic varices due to cirrhosis can be difficult to
manage. We report our experience of uncontrolled bleeding from ectopic varices
treated with transjugular intrahepatic porto-systemic shunt (TIPS). METHODS: We
selected the 21 cirrhotics who underwent TIPS for bleeding ectopic varices from
our database: Child-Pugh grade A (2), B (11) and C (8). Site of bleeding was
rectal (11), colonic (2), ileal 1, jejunal 1, duodenal 1, and stomal (5).
RESULTS: TIPS was performed successfully in 19/21 (90%) patients. All except 1
had either a reduction in portosystemic pressure gradient </= 12mmHg (n=12) or
reduction by 25-50% of baseline (n=6). TIPS alone was used in 12/19: 7 of these
12 had no further bleeding; 5 (42%) rebled within 48h, and had embolisation, 4
without further bleeding. In 7 of 19, TIPS and embolisation were performed
together: 2 patients (28%) rebled; further embolisation stopped the bleeding.
CONCLUSIONS: Ectopic varices do rebleed despite a reduction of porto-systemic
pressure gradient </= 12mmHg or by 25-50% of baseline, following TIPS.
Embolisation stopped bleeding in all but 1 patient. We recommend performing
embolisation at the time of the initial TIPS to control bleeding from ectopic
varices.
Gastrointest Endosc. 2004 Aug;60(2):180-5.
Endoscopic sphincterotomy vs. endoscopic papillary balloon
dilation for choledocholithiasis in patients with liver cirrhosis and
coagulopathy.
Park do H, Kim MH, Lee SK, Lee SS, Choi JS, Song MH, Seo DW, Min YI.
Current affiliation: Department of Internal Medicine, University of Ulsan
College of Medicine, Asan Medical Center, Seoul, Korea.
BACKGROUND: To determine whether endoscopic papillary balloon dilation decreases
the risk of hemorrhage without increasing the risk of acute pancreatitis, the
results of endoscopic papillary balloon dilation were compared with those of
endoscopic biliary sphincterotomy in patients with cirrhosis and coagulopathy.
METHODS: Twenty-one patients with liver cirrhosis with coagulopathy had
endoscopic papillary balloon dilation for choledocholithiasis from January 2001
to September 2003. Twenty patients with cirrhosis and coagulopathy who underwent
endoscopic biliary sphincterotomy from January 1998 to December 2000, served as
a historical control group. RESULTS: The rate of endoscopic biliary
sphincterotomy related hemorrhage was 30% (6/20), whereas the rate for
endoscopic papillary balloon dilation related hemorrhage was 0% (p=0.009). With
regard to rates of hemorrhage in relation to Child-Pugh class, most (n=5) of the
bleeding complications occurred in patients with Child-Pugh class C cirrhosis;
bleeding occurred in only one patient with Child-Pugh B cirrhosis. There was no
significant difference between the endoscopic biliary sphincterotomy and the
endoscopic papillary balloon dilation groups for procedure-related pancreatitis
(10% vs. 4.7%, respectively; p>0.05). CONCLUSIONS: Endoscopic papillary balloon
dilation may significantly reduce the risk of bleeding compared with endoscopic
biliary sphincterotomy in patients with advanced cirrhosis and coagulopathy. In
these patients, the substitution of endoscopic papillary balloon dilation for
endoscopic biliary sphincterotomy is recommended for treatment of
choledocholithiasis.
Expert Opin Biol Ther. 2004 Jul;4(7):1073-91.
Gene therapy of liver diseases.
Prieto J, Qian C, Hernandez-Alcoceba R, Gonzalez-Aseguinolaza G, Mazzolini G,
Sangro B, Kramer MG.
Clinica Universitaria de Navarra, Department of Internal Medicine, Avda. Pio XII
36, 31008 Pamplona, Spain. mgkramer@unav.es
Many liver diseases lack satisfactory treatment and alternative therapeutic
options are urgently needed. Gene therapy is a new mode of treatment for both
inherited and acquired diseases, based on the transfer of genetic material to
the tissues. Genes are incorporated into appropriate vectors in order to
facilitate their entrance and function inside the target cells. Gene therapy
vectors can be constructed on the basis of viral or non-viral molecular
structures. Viral vectors are frequently used, due to their higher transduction
efficiency. Both the type of vector and the expression cassette determine the
duration, specificity and inducibility of gene expression. A considerable number
of preclinical studies indicate that a great variety of liver diseases,
including inherited metabolic defects, chronic viral hepatitis, liver cirrhosis
and primary and metastatic liver cancer, are amenable to gene therapy. Gene
transfer to the liver can also be used to convert this organ into a factory of
secreted proteins needed to treat conditions that do not affect the liver
itself. Clinical trials of gene therapy for the treatment of inherited diseases
and liver cancer have been initiated but human gene therapy is still in its
infancy. Recent progress in vector technology and imaging techniques, allowing
in vivo assessment of gene expression, will facilitate the development of
clinical applications of gene therapy.
-
Chest. 2004 Jul;126(1):142-8.
Outcome analysis of cirrhotic patients undergoing chest tube
placement.
Liu LU, Haddadin HA, Bodian CA, Sigal SH, Korman JD, Bodenheimer HC Jr, Schiano
TD.
Division of Liver Diseases, Mount Sinai Medical Center, New York, NY 10029, USA.
OBJECTIVES: Patients with cirrhosis can acquire pulmonary conditions that may or
may not be related to their illness. Although posing a greater risk for
complications, chest tubes are sometimes placed as treatment for hepatic
hydrothorax and other pulmonary conditions. The aim of this study was to analyze
the outcomes of chest tube placement in cirrhotic patients. METHODS: A
retrospective analysis was performed of 59 adults with cirrhosis undergoing
chest tube placement. Variables that were investigated included reason for chest
tube placement, complications developing while having the tube in place, and
outcome. RESULTS: The 59 subjects were classified as having Child-Turcotte-Pugh
(CTP) class A cirrhosis (n = 3), CTP class B cirrhosis (n = 31), and CTP class C
cirrhosis (n = 25). Indications for having a chest tube placed were hepatic
hydrothorax (n = 24), pneumothorax (n = 9), empyema (n = 8), video-assisted
thoracoscopy (VAT) [n = 7], non-VAT (n = 5), and hemothorax (n = 3). The CTP
class A subjects had their chest tubes removed without further complications
early in the course, and were excluded from further statistical analysis.
Twenty-five subjects (42%) had significant pleural effusions requiring chest
tube placement. Among the CTP class B and class C subjects, the median duration
with chest tube in place was 5.0 days (range, 1 to 53 days). Serum total
bilirubin levels, presence of portosystemic encephalopathy, and CTP C
classification were predictors of mortality. Mortalities were seen in 5 of 31
CTP class B subjects (16%), and 10 of 25 CTP class C subjects (40%). The tubes
were successfully removed in a total of 39 subjects (66%) with no further
procedure. Forty-seven subjects (80%) acquired one or more of the following
complications: renal dysfunction, electrolyte imbalances, and infection.
CONCLUSIONS: When placed for all indications, chest tubes may be successfully
removed in the majority of cirrhotic patients. However, a third of all patients
still die with the chest tube still in place. Failure to remove the chest tube
increases mortality in patients with increasing severity of liver disease.
Hepatology. 2004 Jul;40(1):65-72.
Ligation versus propranolol for the primary prophylaxis of
variceal bleeding in cirrhosis.
Schepke M, Kleber G, Nurnberg D, Willert J, Koch L, Veltzke-Schlieker W,
Hellerbrand C, Kuth J, Schanz S, Kahl S, Fleig WE, Sauerbruch T; German Study
Group for the Primary Prophylaxis of Variceal Bleeding.
Department of Internal Medicine I, University of Bonn, Bonn, Germany.
In this randomized controlled multicenter trial, we compared endoscopic variceal
banding ligation (VBL) with propranolol (PPL) for primary prophylaxis of
variceal bleeding. One hundred fifty-two cirrhotic patients with 2 or more
esophageal varices (diameter >5 mm) without prior bleeding were randomized to
VBL (n = 75) or PPL (n = 77). The groups were well matched with respect to
baseline characteristics (age 56 +/- 10 years, alcoholic etiology 51%,
Child-Pugh score 7.2 +/- 1.8). The mean follow-up was 34 +/- 19 months. Data
were analyzed on an intention-to-treat basis. Neither bleeding incidence nor
mortality differed significantly between the 2 groups. Variceal bleeding
occurred in 25% of the VBL group and in 29% of the PPL group. The actuarial
risks of bleeding after 2 years were 20% (VBL) and 18% (PPL). Fatal bleeding was
observed in 12% (VBL) and 10% (PPL). It was associated with the ligation
procedure in 2 patients (2.6%). Overall mortality was 45% (VBL) and 43% (PPL)
with the 2-year actuarial risks being 28% (VBL) and 22% (PPL). 25% of patients
withdrew from PPL treatment, 16% due to side effects. In conclusion, VBL and PPL
were similarly effective for primary prophylaxis of variceal bleeding. VBL
should be offered to patients who are not candidates for long-term PPL
treatment.
Hepatology. 2004 Jul;40(1):55-64.
Midodrine, octreotide, albumin, and TIPS in selected patients
with cirrhosis and type 1 hepatorenal syndrome.
Wong F, Pantea L, Sniderman K.
Division of Gastroenterology, Department of Medicine, Toronto General Hospital,
University of Toronto, Toronto, Ontario, Canada. florence.wong@utoronto.ca
Hepatorenal syndrome (HRS) is a functional renal disorder complicating
decompensated cirrhosis. Treatments to date, except liver transplantation, have
been able to improve but not normalize renal function. The aim of this study was
to determine the efficacy of transjugular intrahepatic portosystemic stent shunt
(TIPS) as a treatment for type 1 HRS in ascitic cirrhotic patients, following
improvement in systemic hemodynamics with a combination of midodrine, octreotide,
and albumin (medical treatment). Fourteen ascitic cirrhotic patients with type 1
HRS received medical therapy until their serum creatinine reached below 135
micromol/L for at least 3 days, followed by a TIPS if there were no
contraindications. Patients were assessed before and after medical treatment, as
well as at 1 week and 1, 3, 6, and 12 months post-TIPS with measurements of
renal function, sodium handling, systemic hemodynamics, central blood volume,
and hormonal markers. Medical therapy for 14 +/- 3 days improved renal function
(serum creatinine: 233 +/- 29 micromol/L vs. 112 +/- 8 micromol/L, P =.001) and
renal sodium excretion (5 +/- 2 mmol/d vs. 9 +/- 2 mmol/d, P =.002) in 10 of the
14 patients. TIPS insertion in five of the responders further improved renal
function and sodium excretion, so that by 12 months post-TIPS, glomerular
filtration rate (96 +/- 20 mL/min, P <.01 vs. pre-TIPS) and urinary sodium
excretion (119 +/- 15 mmol/d, P <.01 vs. pre-TIPS) were normal, associated with
normalization of plasma renin and aldosterone levels and elimination of ascites.
In conclusion, TIPS is an effective treatment for type 1 HRS in suitable
patients with cirrhosis and ascites, following the improvement of renal function
with combination therapy of midodrine, octreotide, and albumin.
Gastroenterology. 2004 Jun;126(7):1740-9.
Long-term benefit of interferon alpha therapy of chronic
hepatitis D: regression of advanced hepatic fibrosis.
Farci P, Roskams T, Chessa L, Peddis G, Mazzoleni AP, Scioscia R, Serra G, Lai
ME, Loy M, Caruso L, Desmet V, Purcell RH, Balestrieri A.
Dipartimento di Scienze Mediche, Universita di Cagliari, SS 554 Bivio Sestu,
09042 Cagliari, Italy. farcip@pacs.unica.it
BACKGROUND & AIMS: Little is known about the long-term effects of interferon
alpha on clinical outcome and survival of patients with chronic hepatitis D.
METHODS: Thirty-six patients with chronic hepatitis D who participated in a
randomized controlled trial of a 48-week course of high (9 million units) or low
(3 million units) doses of interferon alpha or no treatment were followed for an
additional 2 to 14 years. RESULTS: Long-term survival was significantly longer
in the high-dose group than in untreated controls (P = 0.003) or in the low-dose
group (P = 0.019) but did not differ between patients treated with 3 million
units and controls. Among surviving patients at 12 years of follow-up, a
biochemical response was present in 7 of 12 treated with 9 million units, in 2
of 4 who received 3 million units, and in none of 3 controls. Long-term alanine
aminotransferase (ALT) normalization correlated with improved hepatic function
and loss of IgM antibody to hepatitis delta antigen (anti-HD). Patients in the
high-dose group had a sustained decrease in HDV replication (P = 0.008), leading
to clearance of HDV RNA and, eventually, hepatitis B virus (HBV) in some
patients, as well as a dramatic improvement in liver histology with respect to
activity grade (P = 0.0004) and fibrosis stage (P = 0.007). Strikingly, we
documented an absence of fibrosis in the final biopsy of 4 patients with a
long-term biochemical response and an initial diagnosis of active cirrhosis.
CONCLUSIONS: High doses of interferon alpha-2a significantly improved the
long-term clinical outcome and survival of patients with chronic hepatitis D,
even though the majority had active cirrhosis before the onset of therapy.
Am J Gastroenterol. 2004 Jun;99(6):1105-10.
Extracorporeal albumin dialysis: a procedure for prolonged relief
of intractable pruritus in patients with primary biliary cirrhosis.
Pares A, Cisneros L, Salmeron JM, Caballeria L, Mas A, Torras A, Rodes J.
Liver Unit, Institut Clinic de Malalties Digestives, Hospital Clinic, Barcelona,
Spain.
BACKGROUND AND AIMS: Pruritus is a distressing symptom in patients with primary
biliary cirrhosis, and when uncontrollable it is an indication for liver
transplantation. Since pruritus can result from unknown substances that
accumulate systemically as a consequence of impaired biliary secretion, we have
assessed whether a new extracorporeal albumin dialysis (ECAD) procedure, the
molecular-adsorbing recirculating system-MARS, has any effect on pruritus of
cholestasis. METHODS: Four patients with primary biliary cirrhosis and resistant
pruritus were treated with two 7-h ECAD sessions 1 day apart. Pruritus was
recorded from 15 days before the first session, before and after each session,
and during the follow-up using a visual analogue scale (VAS). Standard liver
tests as well as serum bile acid levels were also measured. RESULTS: There was a
clear association between ECAD treatment and relief of itching, which promptly
disappeared in two patients, or decreased markedly in the other two. One patient
was free of pruritus for 18 months except for short periods with mild pruritus.
The second patient experienced amelioration of itching, which almost disappeared
completely and recurred mildly 4 months later. In the other two patients
pruritus was alleviated markedly after ECAD but gradually recurred. These two
patients were treated again 9 and 7 months later with favorable effects on
pruritus. The scratching skin lesions improved or disappeared in parallel with
the alleviation of itching. The albumin dialysis procedure did not result in
liver test changes, except for circulating bile acids, which decreased in all
the patients. No significant adverse effects were observed. CONCLUSIONS: The
ECAD procedure seems to be an effective alternative for the treatment of
patients with pruritus of cholestasis who do not respond to other therapeutic
methods.
Eur J Gastroenterol Hepatol. 2004 Jun;16(6):567-70.
Nitric oxide and renal function in cirrhotic patients with
ascites: from physiopathology to practice.
Grange JD, Amiot X.
Department of Gastroenterology and Hepatology, Hopital Tenon, Paris, France.
jean-didier.grange@tnn.ap-hop-paris.fr
Patients with cirrhosis and ascites show systemic and splanchnic arterial
vasodilation, which causes a reduction in effective arterial blood volume and
the activation of hormonal anti-natriuretic systems. Renal impairment is the
most important predictor of hospital mortality in cirrhotic patients with SBP.
In patients with SBP, the inflammatory response to the infection (TNF-alpha,
IL-6) may be an important mechanism of renal dysfunction. Ascitic-fluid NO
metabolites are related independently to the development of renal impairment.
Treatment of SBP with intravenous albumin in addition to cefotaxime prevents
renal impairment and reduces mortality in comparison with treatment with
cefotaxime alone. As soon as ascites develops, liver transplantation should be
considered in eligible patients, especially when local mean waiting times exceed
life expectancy. Nitric oxide (NO), tumour necrosis factor alpha (TNF-alpha) and
interleukin-6 (IL-6) have been implicated in the pathogenesis of circulatory
alterations observed in cirrhotic patients with ascites. Kidney failure is one
of the main factors associated with mortality in patients with end-stage liver
disease developing complications, particularly severe infections and variceal
haemorrhage. Renal impairment occurs in patients with the highest concentration
of cytokines in plasma and ascitic fluid and is associated with marked
activation of the renin-angiotensin system. In patients with spontaneous
bacterial peritonitis (SBP), serum and ascitic fluid levels of NO metabolites
(nitrites and nitrates) were higher than those of patients with sterile ascites,
and renal impairment is considered to be caused by a decrease in effective
arterial blood volume as a result of the infection. The administration of
albumin prevents deterioration of renal function and reduces mortality in these
patients. However, SBP and renal dysfunction are late complications in the
course of liver cirrhosis. As soon as ascites develops, liver transplantation
should be considered in eligible patients, especially when local mean waiting
times exceed life expectancy. A better knowledge of metabolic disorders
associated with the early stage of cirrhosis is essential for the development of
optimal therapeutic strategies for the prophylaxis and treatment of portal
hypertension and its complications.
Hepatology. 2004 Apr;39(4):915-23.
A randomized controlled trial of colchicine plus
ursodiol versus methotrexate plus ursodiol in primary biliary
cirrhosis: ten-year results.
Kaplan MM, Cheng S, Price LL, Bonis PA.
Division of Gastroenterology, Department of Medicine and the Tupper
Research Institute, New England Medical Center and Tufts University
School of Medicine, Boston, Massachusetts, USA. mkaplan@tufts-nemc.org
Primary biliary cirrhosis frequently progresses despite treatment
with ursodeoxycholic acid (UDCA), the only approved therapy. Previous
studies suggested that colchicine and methotrexate may improve
biochemical tests of liver function, symptoms, and liver histology.
The aim of the present study was to determine if the addition
of colchicine or methotrexate to UDCA would improve survival free
of liver transplantation. Eighty-five patients with histologically
confirmed primary biliary cirrhosis whose serum alkaline phosphatase
levels were at least twice the normal level and who were not yet
candidates for liver transplantation were randomly assigned to
receive colchicine or methotrexate in a double-blind study. UDCA
was administered to all patients after 2 years. The primary end
point was survival free of liver transplantation. Patients were
followed up for a total of up to 10 years or until treatment failure.
Data were analyzed on an intention-to-treat basis. Transplant-free
survival was similar in both groups: 0.57 for colchicine plus
UDCA and 0.44 for methotrexate plus UDCA, results that are similar
to those predicted by the Mayo prognostic model. Significant improvement
in liver biochemical tests and liver histology was observed in
a subset of patients in both treatment groups who remained in
the study for all 10 years. In conclusion, neither colchcine plus
UDCA nor methotrexate plus UDCA improved survival beyond that
predicted by the Mayo prognostic model. However, clinical, histologic,
and biochemical improvement observed among those who remained
in the study for 10 years suggests a possible benefit of these
drugs in a subset of patients.
Liver Transpl. 2004 Apr;10(4):564-70.
Two-stage total hepatectomy and liver transplantation
for acute deterioration of chronic liver disease: A new bridge
to transplantation.
Guirl MJ, Weinstein JS, Goldstein RM, Levy MF, Klintmalm
GB.
Department of Internal Medicine, Division of Gastroenterology,
Methodist Dallas Hospital, Dallas, TX.
Two-stage total hepatectomy and liver transplantation has been
reported for acute liver disease such as fulminant hepatic failure,
primary graft failure, severe hepatic trauma, and spontaneous
hepatic rupture secondary to hemolysis, elevated liver function
tests, low platelets syndrome, and preeclampsia. This is the first
report of patients with cirrhosis to undergo a 2-stage total hepatectomy
and liver transplantation. From 1984 to 2002, our institution
performed 2008 orthotopic liver transplantations. We identified
4 patients with chronic liver disease who underwent a 2-stage
hepatectomy and liver transplantation. This is a retrospective
review of these 4 patients and a review of the literature on this
procedure. All 4 patients were young men with an age range of
29-31 years and had underlying cirrhosis as well as a previous
transjugular intrahepatic portosystemic shunt (TIPS)procedure.
Acute decompensation fulfilling Ringes' criteria for toxic liver
syndrome secondary to an upper gastrointestinal bleed occurred
in all patients. The approximate average time between hepatectomy
and liver transplantation was 20 hours (range: 8-42 hours). In
all cases, the explanted liver showed histological changes of
acute hepatic necrosis within the background of cirrhosis. After
hepatectomy, vasopressor requirements were well documented in
2 patients. For 1 patient, there was a clear improvement in their
hemodynamic status. The mean hospital stay of the 4 patients was
63 days. All patients were discharged from the hospital and are
alive and well with adequate liver function at 6 to 37 months
follow-up. Two-stage total hepatectomy and liver transplantation
may be a life-saving procedure in highly selected cirrhotic patients
with acute hepatic decompensation and multiorgan dysfunction.
(Liver Transpl 2004;10:564-570.)
Liver Transpl. 2004 Apr;10(4):488-91.
Immunosuppression affects the rate of recurrent
primary biliary cirrhosis after liver transplantation.
Neuberger J, Gunson B, Hubscher S, Nightingale P.
Liver Unit, Queen Elizabeth Hospital, Birmingham, UK.
Identifying the risk factors associated with recurrence of
primary biliary cirrhosis after liver transplantation may affect
immunosuppression and increase understanding of the pathogenesis.
Four hundred eighty-five patients with PBC were followed for a
median of 79 months after transplantation; histological evidence
of recurrence was found in 23%. On multivariate analysis, the
only risk factor identified with recurrence was the type of calcineurin
inhibitor used. The odds ratio for recurrence on tacrolimus was
2.73 (95% confidence interval: 1.84-4.10) compared with cyclosporine.
For those receiving cyclosporine, the median time to recurrence
was 123 months and for those on tacrolimus 62 months (P <.001).
Reasons for this difference between the 2 calcineurin inhibitors
are not clear. (Liver Transpl 2004;10:488-491.)
Ann Surg. 2004 Feb;239(2):194-201.
Abdominal drainage after hepatic resection is
contraindicated in patients with chronic liver diseases.
Liu CL, Fan ST, Lo CM, Wong Y, Ng IO, Lam CM, Poon RT,
Wong J.
Department of Surgery, University of Hong Kong Medical Centre,
Queen Mary Hospital, Hong Kong, China. clliu@hkucc.hku.hk
OBJECTIVE: The aim of this study was to determine whether abdominal
drainage is beneficial after elective hepatic resection in patients
with underlying chronic liver diseases. SUMMARY BACKGROUND DATA:
Traditionally, in patients with chronic liver diseases, an abdominal
drainage catheter is routinely inserted after hepatic resection
to drain ascitic fluid and to detect postoperative hemorrhage
and bile leakage. However, the benefits of this surgical practice
have not been evaluated prospectively. PATIENTS AND METHODS: Between
January 1999 and March 2002, 104 patients who had underlying chronic
liver diseases were prospectively randomized to have either closed
suction abdominal drainage (drainage group, n = 52) or no drainage
(nondrainage group, n = 52) after elective hepatic resection.
The operative outcomes of the 2 groups of patients were compared.
RESULTS: Fifty-seven (55%) patients had major hepatic resection
with resection of 3 Coiunaud's segments or more. Sixty-nine (66%)
patients had liver cirrhosis and 35 (34%) had chronic hepatitis.
Demographic, surgical, and pathologic details were similar between
both groups. The primary indication for hepatic resection was
hepatocellular carcinoma (n = 100, 96%). There was no difference
in hospital mortality between the 2 groups of patients (drainage
group, 6% vs. nondrainage group, 2%; P = 0.618). However, there
was a significantly higher overall operative morbidity in the
drainage group (73% vs. 38%, P < 0.001). This was related to
a significantly higher incidence of wound complications in the
drainage group compared with the nondrainage group (62% vs. 21%,
P < 0.001). In addition, a trend toward a higher incidence
of septic complications in the drainage group was observed (33%
vs. 17%, P = 0.07). The mean (+/- standard error of mean) postoperative
hospital stay of the drainage group was 19.0 +/- 2.2 days, which
was significantly longer than that of the nondrainage group (12.5
+/- 1.1 days, P = 0.005). With a median follow-up of 15 months,
none of the 51 patients with hepatocellular carcinoma in the drainage
group developed metastasis at the drain sites. On multivariate
analysis, abdominal drainage, underlying liver cirrhosis, major
hepatic resection, and intraoperative blood loss of >1.5L were
independent and significant factors associated with postoperative
morbidity. CONCLUSION: Routine abdominal drainage after hepatic
resection is contraindicated in patients with chronic liver diseases.
Rom J Gastroenterol. 2003 Dec;12(4):297-302.
Cirrhosis and bacterial infections.
Vilstrup H.
Department of Medicine V, Aarhus University Hospital, Denmark.
vilstrup@akh.aaa.dk
Half of cirrhosis patients die within two years after diagnosis,
in most cases from cirrhosis related causes; most frequently variceal
bleeding closely followed by infections. There seems to exist
associations between infection and other complications such as
malnutrition, hepatic encephalopathy and variceal bleeding. Cirrhosis
patients have an acquired immune deficiency because of dyshomeostasis
and malnutrition. All host defence systems are compromised, e.g.
the acute phase response, and macrophage, neutrocyte, and lymphocyte
functions. Simultaneously, there is increased microbiotic invasion,
due to increased nosocomial exposure, intestinal translocation,
aspiration, skin lesions, and trauma. Compared to the background
population, the mortality of infections is more than 20 times
increased in cirrhosis. The incidence of peritonitis, bacteremia,
urinary tract infection, pneumonia, meningitis, tuberculosis,
liver abscess is increased more than tenfold, and the mortality
of each episode 3-10 times higher. The systemic response and accompanying
classical symptoms are usually weakened. When positive isolates
can be obtained the flora tends to be of an opportunistic nature.
Infection should be suspected in any cirrhotic patient with an
unexpected deterioration of clinical course. Treatment should
be started on suspicion and with large dose broad-spectrum antibiotics
(avoiding aminoglycosides). Antibiotic prophylaxis is efficacious
at variceal bleeding, recurrent peritonitis, and at very low protein
ascites, but otherwise is associated with risk of infection with
multi-resistant strains.
Acta Med Croatica. 2003;57(3):221-5.
[Primary biliary cirrhosis]
[Article in Croatian]
Cukovic-Cavka S.
Zavod za gastroenterologiju, Klinicki bolnicki centar Zagreb,
Kispaticeva 12, 10000 Zagreb, Hrvatska.
Primary biliary cirrhosis is an autoimmune chronic cholestatic
liver disease of unknown cause that usually affects middle-aged
women. It is characterized by inflammatory destruction of the
interlobular and septal bile ducts, which leads to chronic cholestasis
and cirrhosis. The diagnosis should be considered in the setting
of elevated alkaline phosphatase, immunoglobulin M level and the
presence of antimitochondrial antibody in serum. Ursodeoxycholic
acid is the only medication of proven benefit for these patients.
Liver transplantation is only therapeutic option for patients
who have end-stage disease.
Hepatogastroenterology. 2003 Nov-Dec;50(54):2013-6.
Long-term follow-up of patients with liver cirrhosis
after endoscopic esophageal varices ligation therapy: comparison
with ethanol injection therapy.
Okano H, Shiraki K, Inoue H, Kawakita T, Deguchi M, Sugimoto
K, Sakai T, Ohmori S, Murata K, Nakano T.
First Department of Internal Medicine, Mie University School of
Medicine, 2-174 Edobashi, Tsu, Mie 514-8507, Japan.
BACKGROUND/AIMS: Esophageal variceal hemorrhage is the most
dreaded complication of liver disease. Prevention or emergency
therapy of bleeding is important. METHODOLOGY: A group of 217
patients underwent endoscopic esophageal variceal therapy including
endoscopic ethanol injection, endoscopic esophageal variceal ligation,
or a combination of the two. RESULTS: Esophageal varices were
eradicated by endoscopic esophageal variceal ligation with the
least sessions required, and associated complications with endoscopic
esophageal variceal ligation therapy were lower than with the
other two approaches. However, the cumulative recurrence-free
period of esophageal varices was significantly higher after endoscopic
ethanol injection than after endoscopic esophageal variceal ligation
and in some cases F3 varices were observed post-endoscopic esophageal
variceal ligation hemorrhage. A combined endoscopic esophageal
variceal ligation and endoscopic ethanol injection therapy had
no advantage with respect to cumulative recurrence-free rate,
session number, or complication frequency, relative to either
therapy alone. CONCLUSIONS: While the combined observations indicate
that endoscopic esophageal variceal ligation is safe and simple,
we should consider additional therapy to achieve complete mucosal
fibrosis of the esophagus after endoscopic esophageal variceal
ligation.
Intervirology. 2003;46(6):388-93.
Lamivudine therapy for decompensated liver cirrhosis
related to hepatitis B virus infection.
Lee HC, Suh DJ.
Division of Gastroenterology, Department of Internal Medicine,
Asan Medical Center, University of Ulsan College of Medicine,
388-1 Pungnap-song, Songpa-gu, Seoul, Korea.
Chronic hepatitis B virus (HBV) infection is the major cause
of chronic liver disease worldwide. Although the clinical course
of HBV infection varies widely, the prognosis of decompensated
liver cirrhosis is quite poor and the 5-year survival rate has
been estimated to be only 14-35%. While the ultimate treatment
of decompensated cirrhosis is orthotopic liver transplantation
(OLT), recent studies have suggested that lamivudine can also
improve the clinical outcomes in this group of patients. Lamivudine
rapidly suppresses HBV replication and can improve several parameters
of liver function tests and afford prolonged periods of pretransplantation
survival. However, the proportion of clinical improvement as defined
by a decrease in Child-Pugh score as well as the prolonged survival
rate varied widely from study to study. These discrepancies might
result from differences in the severity of cirrhosis at entry,
the presence of active viral replication or inflammation, and
the proportions of patients who received OLT during the study
period. Overall, about half of the patients achieved a clinical
improvement with lamivudine therapy. However, data are still lacking
on whether lamivudine can prolong survival before OLT and even
replace OLT. Most of the deaths or clinical improvement occurred
or started to occur within the first 6 months of treatment. Therefore,
OLT should be actively considered in patients with risk factors
for early mortality or those without clinical improvement within
the first 6 months of lamivudine treatment. Copyright 2003 S.
Karger AG, Basel
Am J Gastroenterol. 2003 Nov;98(11):2485-90.
Vitamin E and vitamin C treatment improves fibrosis
in patients with nonalcoholic steatohepatitis.
Harrison SA, Torgerson S, Hayashi P, Ward J, Schenker S.
Brooke Army Medical Center, University of Texas Health Science
Center San Antonio, San Antonio, Texas, USA.
OBJECTIVE: Nonalcoholic steatohepatitis (NASH) is a common
cause of liver disease. Although usually indolent, this disease
can progress to cirrhosis in some patients. There is currently
no proven medical therapy for the treatment of NASH. The aim of
our study was to evaluate the efficacy of combination alpha-tocopherol
(vitamin E) and vitamin C in reducing histologic inflammation
and fibrosis. METHODS: This was a prospective, double-blind, randomized,
placebo-controlled trial with a total enrollment of 49 patients;
45 patients completed the study. All patients were randomized
to receive either vitamins E and C (1000 IU and 1000 mg, respectively)
or placebo daily for 6 months, based on their initial histologic
diagnosis of NASH. Additionally, all patients were given standard
weight-loss counseling and encouraged to follow a low fat diet
(<30 fat g/day). The pre- and posttreatment liver biopsies
were reviewed by a single pathologist, who was blinded to the
patient's medication. Biopsies were scored based on a modification
of the scoring system published by Brunt et al. (Am J Gastroenterol
1999;94:2467-74). A score of 0-4 was possible for fibrosis, and
a score of 0-6 was possible for inflammation and hepatocyte degeneration
and necrosis. In addition, body mass index, glycohemoglobin, lipids,
and liver enzymes were followed throughout the study. RESULTS:
Forty-five patients completed 6 months of therapy without significant
side effects. Vitamin treatment resulted in a statistically significant
improvement in fibrosis score (p=0.002). No changes were noted
in inflammation with treatment.Vitamin E and vitamin C, in the
doses used in this study, were well tolerated and were effective
in improving fibrosis scores in NASH patients. No improvement
in necroinflammatory activity or ALT was seen with this combination
of drug therapy. A larger, multicenter, longer-term trial with
vitamin E and vitamin C seems to be warranted.
Int J Vitam Nutr Res. 2003 Nov;73(6):411-5.
Pilot clinical trial of the use of alpha-tocopherol
for the prevention of hepatocellular carcinoma in patients with
liver cirrhosis.
Takagi H, Kakizaki S, Sohara N, Sato K, Tsukioka G, Tago
Y, Konaka K, Kabeya K, Kaneko M, Takayama H, Hashimoto Y, Yamada
T, Takahashi H, Shimojo H, Nagamine T, Mori M.
First Department of Internal Medicine, Gunma University Faculty
of Medicine, 3-39-15, Showa Machi Maebashi, 371-8511, Japan. htakagi@med.gunma-u.ac.jp
Patients with chronic hepatitis C virus (HCV) infection often
develop liver cirrhosis and hepatocellular carcinoma (HCC). The
purpose of this study was to test the chemopreventive effect of
alpha-tocopherol on hepatocarcinogenesis in patients with liver
cirrhosis and a history of HCV infection. Eighty-three patients
with liver cirrhosis and with positive history of HCV infection
were divided at random into two groups. Forty-four patients were
treated with alpha-tocopherol (Vit E group) while the other 39
were followed as controls. The clinical background (gender, age,
and laboratory data) was similar in the two groups. Serum levels
of alpha-tocopherol, albumin, alanine aminotransferase (ALT),
and total cholesterol and platelet count were measured serially
over a period of five years. The mean serum concentration of alpha-tocopherol
was low in both groups at entry and was significantly higher in
the Vit E group than in the control group one month after treatment.
Platelet count, serum albumin, ALT, and total cholesterol were
not different between the two groups during the five-year period.
Cumulative tumor-free survival and cumulative survival rate tended
to be higher in the Vit E group than in controls, albeit statistically
insignificant. The serum level of alpha-tocopherol was low in
patients with liver cirrhosis and positive for HCV. Although the
administration of alpha-tocopherol normalized the level one month
later, it could neither improve liver function, suppress hepatocarcinogenesis,
nor improve cumulative survival. Patients treated with alpha-tocopherol
tended to live longer without development of HCC but the difference
was not statistically significant.
Dig Liver Dis. 2003 Sep;35(9):660-3.
Is the use of albumin of value in the treatment
of ascites in cirrhosis? The case in favour.
Laffi G, Gentilini P, Romanelli RG, La Villa G.
Department of Internal Medicine, University of Florence School
of Medicine, Viale Morgagni 85, 1-50134 Florence, Italy.
In patients with cirrhosis, ascites accumulates because of
sodium retention, triggered by a reduction of the effective arterial
blood volume, and imbalanced Starling forces in the splanchnic
area due to portal hypertension and hypoalbuminemia. Albumin is
the ideal plasma expander in this setting, since it ameliorates
systemic and reneal haemodynamics, so reducing sodium retention,
and increases oncotic pressure in the splanchnic compartment.
In particular, albumin proved useful in patients treated with
diuretics, as demonstrated by a randomised study performed at
our Instituition in which 126 ascitic inpatients were treated
according to a stepped-care diuretic regimen. In fact, patients
receiving diuretics plus albumin (n = 63) had a higher cummulative
rate of response (p < 0.05) and a shorter hospital stay (20
+/- 1 versus 24 +/- 2 days, p < 0.05) than those given diuretics
alone. Treatment with albumin on an outpatient basis (25 g/week)
resulted in a lower probability of developing ascites (p <
0.02 vs. patients not given albumin) and a lower probability of
readmission (p < 0.02). Patients given albumin also had a better
quality of life. As discussed in another article, evidence also
supports the use of albumin in patients treated for paracentesis,
as well as in patients with spontaneous peritonitis or hepatorenal
syndrome.
Schweiz Rundsch Med Prax. 2003 Aug 27;92(35):1427-34.
[Complications of liver cirrhosis: portal hypertension,
gastroesophageal varices and ascites]
[Article in German]
Schuster MJ.
Medizinische Klinik Fachbereich Gastroenterologie Stadtische Kliniken
Esslingen Akademisches Lehrkrankenhaus der Universitat Tubingen
Hirschlandstrasse 97 D-73730 Esslingen.
Patients with cirrhosis of the liver are at high risk of a
large variety of complications. Especially the development of
portal hypertension, followed by gastroesophageal varicosis and
ascites are potentially life threatening problems. In the treatment
of gastroesophageal varicosis primary prophylaxis to prevent a
first bleeding episode, acute therapy for bleeding varices, and
secondary prophylaxis to prevent patients from rebleeding have
to be considered. While treating patients with ascites the high
frequency of side effects induced by diuretics has to be taken
into account. In addition, the diagnosis of spontaneous bacterial
peritonitis must not be missed. Hepatorenal syndrome, a typical
complication of advanced cirrhosis is especially difficult to
treat and is considered an indication for liver transplantation.
Hepatogastroenterology. 2003 Sep-Oct;50(53):1556-9.
Long-term follow-up of patients with liver cirrhosis
after endoscopic ethanol injection sclerotherapy for esophageal
varices.
Okano H, Shiraki K, Inoue H, Kawakita T, Deguchi M, Sugimoto
K, Sakai T, Ohmori S, Murata K, Nakano T.
First Department of Internal Medicine, Mie University School of
Medicine, 2-174 Edobashi, Tsu, Mie 514-8507, Japan.
BACKGROUND/AIMS: Esophageal variceal hemorrhage is a severe
complication of liver cirrhosis, and therapy for acute bleeding
and prevention of hemorrhage are important. In this study, we
evaluated the long-term cumulative survival rate of patients with
esophageal varices after treatment with endoscopic ethanol injection
sclerotherapy (EIS group) or pharmacological therapy (non-EIS
group). METHODOLOGY: All 110 patients were treated for their esophageal
varices and their prognosis and complications were analyzed during
the follow-up period. RESULTS: The cumulative survival rate in
the primary preventive EIS group was superior to that in the non-EIS
group. The preventive EIS group had greater long-term survival
rate than those treated on an emergency group. With respect to
emergency therapy, the EIS group had better survival rates than
the non-EIS group during the two-year follow-up period after esophageal
variceal therapy. CONCLUSIONS: We conclude that primary preventive
EIS is an effective therapy for survival of patients with esophageal
varices over a long-term period.
Br J Surg. 2003 Aug;90(8):950-5.
Interstitial laser coagulation with temporary
hepatic artery occlusion for patients with cirrhosis and irresectable
hepatoma.
Verhoef C, Kuiper JW, Heisterkamp J, de Man RA, Pattynama
PM, IJzermans JN.
Department of Surgery, Erasmus Medical Centre, Rotterdam, The
Netherlands.
BACKGROUND: The aim was to determine the degree of local control
of hepatocellular carcinoma (HCC) in patients with cirrhotic liver
disease when treated with ultrasonographically guided interstitial
laser coagulation (ILC) with temporary hepatic artery occlusion.
METHODS: Sixteen patients with 24 HCC tumours were treated. Follow-up
was by computed tomography or magnetic resonance imaging every
3 months. RESULTS: Nineteen of 24 tumours showed complete necrosis
immediately after treatment, and there was no tumour recurrence
during follow-up (mean 14 months, median 12 months). No effect
on liver function was observed after 1 week and there was no death.
In 13 of the 16 patients, new HCC foci developed at other sites.
CONCLUSION: Percutaneous ILC combined with temporary hepatic artery
occlusion during a single session is an effective local treatment
for HCC nodules smaller than 5 cm. However, new HCC lesions develop
in the majority of patients, which underscores the need for adjuvant
therapy or repeated treatment in these patients. Copyright 2003
British Journal of Surgery Society Ltd. Published by John Wiley
& Sons, Ltd.
Ann Intern Med. 2003 Aug 5;139(3):186-93.
The effect of selective intestinal decontamination
on the hyperdynamic circulatory state in cirrhosis. A randomized
trial.
Rasaratnam B, Kaye D, Jennings G, Dudley F, Chin-Dusting
J.
Alfred Hospital and Baker Medical Research Institute, Prahran,
Victoria, Australia.
BACKGROUND: Peripheral vasodilatation is central to the pathogenesis
of the accompanying hyperkinetic circulatory state and portal
hypertension in cirrhotic patients. Selective intestinal decontamination
with norfloxacin has been demonstrated to partially correct nitric
oxide production in the forearm vasculature of cirrhotic patients.
OBJECTIVE: To examine the effects of selective intestinal decontamination
on regional and systemic hemodynamics in cirrhotic patients. DESIGN:
Randomized, double-blind, placebo-controlled, crossover study.
SETTING: Alfred Hospital, Melbourne, Australia. PATIENTS: 14 patients
with alcohol-related cirrhosis and 14 matched healthy controls.
INTERVENTION: Norfloxacin, 400 mg twice daily, for 4 weeks. MEASUREMENTS:
Venous occlusion plethysmography was used to determine forearm
blood flow. Cardiac output and the hepatic venous pressure gradient
were determined after cardiac catheterization. Glomerular filtration
rate was assessed by measuring inulin clearance. Serum levels
of endotoxin were determined by chromogenic Limulus amebocytelysate
assay. RESULTS: Norfloxacin significantly diminished serum endotoxin
levels (average change, -2.14 EU/mL [95% CI, -3.6 to -0.68 EU/mL]).
Derived systemic vascular resistance increased significantly with
norfloxacin (2.94 units [CI, 0.74 to 5.11 units]) and was accompanied
by an increase in mean arterial pressure (8.70 mm Hg [CI, 2.65
to 14.73]), a trend toward decreased cardiac output (-1.207 L/min
[range, 0.05 to -2.37 L/min]), a decrease in forearm blood flow
(-0.99 mL/100 mL per min [CI, -1.80 to -0.17 mL/100 mL per min]),
and a trend toward reduced hepatic venous pressure gradient (-2.43
mm Hg [CI, -5.2 to 0.34 mm Hg]). Norfloxacin did not significantly
alter glomerular filtration rate. CONCLUSION: Selective intestinal
decontamination with norfloxacin partially reverses the hyperdynamic
circulatory state in cirrhotic patients without harming splanchnic
or renal hemodynamics.
Dig Dis Sci. 2003 Jul;48(7):1425-30.
Regression of fibrosis in chronic hepatitis C
after therapy with interferon and ribavirin.
Arif A, Levine RA, Sanderson SO, Bank L, Velu RP, Shah
A, Mahl TC, Gregory DH.
Department of Medicine, Division of Gastroenterology, State University
of New York, Upstate Medical University, Syracuse, New York 13210,
USA.
Interferon and ribavirin decrease necroinflammation in chronic
hepatitis C with or without virological clearance; however, reversibility
of fibrosis remains to be established. We evaluated the effect
of combination therapy on virological and liver histopathological
outcomes in 52 naive patients and 79 patients unresponsive to
interferon monotherapy with predominantly genotype 1 chronic hepatitis
C. One hundred four patients completed interferon and ribavirin
treatment after 24-48 weeks. Fifty-six paired liver biopsies (mean
biopsy interval 28 months) were assessed by the Ishak score. Sustained
virological responses were 37% in naive patients and 22% in re-treated
patients. In virological responders and nonresponders, fibrosis
and necroinflammation scores decreased by -0.91 (P = 0.04) and
-0.5 (P = 0.02) and by -2.8 (P = 0.001) and -0.66 (P = 0.06),
respectively. Interferon and ribavirin had greater benefit on
fibrosis when associated with clearance of HCV RNA. Treatment
strategies in virological nonresponders who show fibrosis regression
should include consideration of maintenance therapy, if such treatment
eventually proves to benefit histological outcomes.
Lancet. 2003 Jul 5;362(9377):53-61.
Primary biliary cirrhosis.
Talwalkar JA, Lindor KD.
Division of Gastroenterology and Hepatology, Mayo Clinic and Foundation,
Rochester, MN 55905, USA.
Primary biliary cirrhosis is a chronic cholestatic liver disease
of adults. This disorder is characterised histologically by chronic
non-suppurative destruction of interlobular bile ducts leading
to advanced fibrosis, cirrhosis, and liver failure. The precise
aetiopathogenesis of primary biliary cirrhosis remains unknown,
although dysregulation of the immune system and genetic susceptibility
both seem to be important. Affected patients are typically middle-aged
women with abnormal serum concentrations of alkaline phosphatase.
Presence of antimitochondrial antibody in serum is almost diagnostic
of the disorder. Identification of primary biliary cirrhosis is
important, because effective treatment with ursodeoxycholic acid
has been shown to halt disease progression and improve survival
without need for liver transplantation. However, therapeutic options
for disease-related complications-including fatigue and metabolic
bone disease-remain unavailable. Mathematical models have been
developed that accurately predict the natural history of primary
biliary cirrhosis in individuals. Despite advances in understanding
of the disease, it remains one of the major indications for liver
transplantation worldwide.
Hepatology. 2003 Jul;38(1):203-9.
Ursodeoxycholic acid therapy and the risk of colorectal
adenoma in patients with primary biliary cirrhosis: an observational
study.
Serfaty L, De Leusse A, Rosmorduc O, Desaint B, Flejou
JF, Chazouilleres O, Poupon RE, Poupon R.
Service d'Hepato-gastroenterologie, Service d'Anatomopathologie,
Hopital Saint-Antoine, INSERM U370, Paris, France. lawrence.serfaty@sat.ap-hop-paris.fr
Ursodeoxycholic acid (UDCA) is the first-line treatment for
primary biliary cirrhosis (PBC). The long-term administration
of UDCA might indirectly favor colon carcinogenesis by increasing
the fecal excretion of secondary bile acids or, in contrast, it
might inhibit colon carcinogenesis, as demonstrated in animal
models. In patients with PBC, we examined the effect of prolonged
UDCA administration on the prevalence and recurrence of colorectal
adenoma and on the proliferation of colon epithelial cells. One
hundred fourteen patients (103 women, 11 men; mean age, 55 years)
with PBC, were enrolled in a colonoscopic surveillance program.
The prevalence of colon adenoma was compared in patients already
treated with UDCA (mean duration 46 months) at the time of colonoscopy
(treated group, n = 52) and in patients undergoing colonoscopy
just prior to treatment initiation (untreated group, n = 62).
The recurrence of adenoma following removal (mean follow-up, 35
months) was compared between UDCA-treated patients and appropriate
age- and gender-matched controls (2/1) selected from a cohort
of 205 patients undergoing polypectomy. Epithelial cell proliferation
was assessed using anti-Ki67 antibodies on colon biopsies from
both treated and untreated patients. Treated and untreated patients
displayed similar demographic characteristics. The prevalence
of colorectal adenomas was 13% in the treated group versus 24%
in the untreated group (P =.16). The colon epithelial cell proliferation
index was significantly lower in treated patients than in untreated
patients (P =.001). Following removal of the adenoma, the probability
of recurrence was significantly lower in patients treated with
UDCA than in controls (7% vs. 28% at 3 years, P =.04). In conclusion,
this study suggests that, in patients with PBC, the prolonged
administration of UDCA (1) is not associated with an increased
prevalence of colorectal adenomas, and (2) significantly decreases
the probability of colorectal adenoma recurrence following removal.
These results are strengthened by the significant reduction in
colon epithelial cell proliferation seen in patients treated with
UDCA.
Hepatology. 2003 Jul;38(1):196-202.
Pharmacokinetics and pharmacodynamic action of
budesonide in early- and late-stage primary
biliary cirrhosis.
Hempfling W, Grunhage F, Dilger K, Reichel C, Beuers U,
Sauerbruch T.
Department of Medicine II, Klinikum Grosshadern, University of
Munich, Munich, Germany.
Budesonide has been discussed as a potential treatment option
in primary biliary cirrhosis (PBC). Therefore, we studied the
pharmacokinetics and pharmacodynamics of budesonide in patients
with PBC stage I/II and stage IV. Twelve patients with early PBC
stage I/II and 7 patients with PBC stage IV under continuous treatment
with ursodeoxycholic acid (UDCA) were enrolled in an exploratory
trial. Each patient received oral budesonide for 3 weeks at weekly
increasing dosages of 3 mg once to thrice per day. Budesonide
and cortisol plasma levels, urinary cortisol excretion, serum
liver tests, and immunoglobulins were determined on days 1, 7,
and 21 of the study. Patients with PBC stage IV showed significantly
higher peak plasma concentrations (4.9 +/- 3.5 vs. 1.5 +/- 0.4
ng/mL; P <.05) and areas under the plasma concentration-time
curves (AUC) (23.2 +/- 16.8 vs. 5.1 +/- 1.4 hours. ng/mL, P <.01,
total AUC extrapolated to infinity [AUC(0- infinity )]) after
a single dose of 3 mg budesonide when compared with patients with
PBC stage I/II. Equally, AUC of budesonide were significantly
increased under a multiple dose regimen on day 21 (14.0 +/- 11.6
vs. 5.0 +/- 1.9 hours. ng/mL, P <.01, AUC at steady state from
dosing time to 8 hours [AUC(ss,0-8 h)]). Higher levels of budesonide
were related to a significant decrease in plasma cortisol and
reduction of urinary cortisol excretion in patients with stage
IV disease. Two patients with stage IV disease developed portal
vein thrombosis (PVT). In conclusion, administration of budesonide
leads to markedly elevated plasma levels in cirrhotic patients
with PBC associated with serious adverse drug reactions. Thus,
further evaluation of combined treatment with UDCA may be considered
in early-stage PBC but not in cirrhotic patients with PBC.
Liver Transpl. 2003 Jul;9(7):733-6.
The effect of immunosuppressive regimens on the
recurrence of primary biliary cirrhosis after liver transplantation.
Levitsky J, Hart J, Cohen SM, Te HS.
Center for Liver Diseases, The University of Chicago Hospitals,
IL 60637, USA.
Recurrence of primary biliary cirrhosis (PBC) has been described
in liver transplant recipients. Type of immunosuppression has
been reported to influence the frequency of recurrence. The aim
of this study is to evaluate the occurrence and pattern of recurrent
PBC in our liver transplant recipients and determine any association
of immunosuppressive agents with its recurrence. Patients who
underwent orthotopic liver transplantation (OLT) for PBC were
identified from the University of Chicago Liver Transplant Database.
Recurrent PBC was diagnosed based on specific pathological criteria.
Of 46 patients who underwent OLT for PBC between 1984 and 2000,
a total of 7 patients (15%) were diagnosed with recurrent PBC
at a median of 78 months (range, 27 to 120 months) after OLT.
Forty-three percent of patients were administered cyclosporine,
whereas 57% were administered tacrolimus before disease recurrence.
Rates of recurrence were not different between patients maintained
on cyclosporine therapy (16%) compared with those maintained on
tacrolimus therapy (18%; P = 1.0). There also was no difference
in frequency of rejection episodes or duration of corticosteroid
therapy between those who did and did not have recurrent PBC.
In conclusion, recurrent PBC developed in a small number of patients
2 years or longer after OLT. In our population, there was no difference
in recurrence rates between those administered cyclosporine or
tacrolimus for immunosuppression.
J Gastroenterol. 2003;38(6):573-8.
Bezafibrate treatment: a new medical approach
for PBC patients?
Kanda T, Yokosuka O, Imazeki F, Saisho H.
First Department of Medicine, Chiba University School of Medicine,
Japan.
BACKGROUND: A new medical approach to primary biliary cirrhosis
(PBC) has been desired. We investigated the feasibility of using
combination ursodeoxycholic acid (UDCA)-bezafibrate therapy in
patients with PBC nonresponsive to UDCA monotherapy. METHODS:
During a 6-month period, 22 PBC patients with elevated serum alkaline
phosphatase (ALP) despite UDCA monotherapy received either UDCA
at 600 mg/day (control group) or UDCA at 600 mg/day plus bezafibrate
at 400 mg/day (bezafibrate group). Each patient underwent detailed
clinical and biochemical evaluation. RESULTS: During treatment,
changes in ALP level were greater in the bezafibrate group than
in the control group (P< 0.01). During and at the end of treatment,
serum ALP levels were significantly lower than those before treatment
in patients receiving UDCA plus bezafibrate (P< 0.05). At the
end of the 6 months, normalization of serum ALP was observed in
5 of 11 (45.4%) patients given bezafibrate and in 2 of 11 (18.1%)
patients not given bezafibrate (P< 0.16). Bile acid proportions
during the combination therapy did not change. Pruritus disappeared
in 1 of 7 bezafibrate-group patients with this symptom. CONCLUSIONS:
UDCA at 600 mg/day plus bezafibrate at 400 mg/day may be considered
as a new therapeutic option for patients with PBC.
Gastroenterology. 2003 Jun;124(7):1792-801.
Nutritional supplementation with branched-chain
amino acids in advanced cirrhosis: a double-blind, randomized
trial.
Marchesini G, Bianchi G, Merli M, Amodio P, Panella C,
Loguercio C, Rossi Fanelli F, Abbiati R; Italian BCAA Study Group.
Department of Internal Medicine, Alma Mater Studiorum University
of Bologna, Bologna, Italy. marchreg@med.unibo.it
BACKGROUND & AIMS: The role of oral supplementation with
branched-chain amino acids (BCAA) in advanced cirrhosis is far
from settled. A nutritional approach might prevent progressive
liver failure and improve nutritional parameters and quality of
life. METHODS: A multicenter, randomized study comparing 1-year
nutritional supplementation with BCAA against lactoalbumin or
maltodextrins was performed in 174 patients with advanced cirrhosis.
Primary outcomes were the prevention of a combined end point (death
and deterioration to exclusion criteria), the need for hospital
admission, and the duration of hospital stay. Secondary outcomes
were nutritional parameters, laboratory data and Child-Pugh score,
anorexia, health-related quality of life, and need for therapy.
RESULTS: Treatment with BCAA significantly reduced the combined
event rates compared with lactoalbumin (odds ratio, 0.43; 95%
confidence interval, 0.19-0.96; P = 0.039) and nonsignificantly
compared with maltodextrins (odds ratio, 0.51; 95% confidence
interval, 0.23-1.17; P = 0.108). The average hospital admission
rate was lower in the BCAA arm compared with control treatments
(P = 0.006 and P = 0.003, respectively). In patients who remained
in the study, nutritional parameters and liver function tests
were, on average, stable or improved during treatment with BCAA
and the Child-Pugh score decreased (P = 0.013). Also, anorexia
and health-related quality of life (SF-36 questionnaire) improved.
Long-term compliance with BCAA was poor. CONCLUSIONS: In advanced
cirrhosis, long-term nutritional supplementation with oral BCAA
is useful to prevent progressive hepatic failure and to improve
surrogate markers and perceived health status. New formulas are
needed to increase compliance.
Liver Transpl. 2003 Jun;9(6):581-6.
Outcome analysis in adult-to-adult living donor
liver transplantation using the left lobe.
Soejima Y, Shimada M, Suehiro T, Hiroshige S, Ninomiya
M, Shiotani S, Harada N, Hideki I, Yonemura Y, Maehara Y.
Department of Surgery and Science, Graduate School of Medical
Sciences, Kyushu University, Fukuoka, Japan. ysoejima@surg2.med.kyushu-u.ac.jp
Graft size problems remain the greatest limiting factor for
expansion of living donor liver transplantation (LDLT) to the
adult population. The result of adult-to-adult LDLT using the
left lobe with special reference to graft size has not been fully
evaluated to date. In this study, we evaluated the outcome of
adult-to-adult LDLT using the left lobe and also analyze the impact
of using small-for-size grafts on outcome. Thirty-six recipients
who underwent adult-to-adult LDLT using the left lobe (n = 14)
or left lobe plus caudate lobe (n = 22) were included in the study.
Variables including preoperative and operative data, patient and
graft survival, complications, and causes of graft loss were studied.
Furthermore, the incidence of small-for-size syndrome and its
impact on graft survival were studied. Mean graft volume (GV)
was 420 +/- 85 g (range, 260 to 620 g), which resulted in 38.2%
+/- 8.1% (range, 22.8% to 53.8%) of the recipient standard liver
volume (SLV). Overall 1-year patient and graft survival rates
were 85.7% and 82.9%, respectively. Seven grafts were lost. Small-for-size
syndrome occurred in 7 of 16 patients (43.8%) with cirrhosis and
only 1 of 20 patients (5.0%) without cirrhosis (P =.005). Recipients
who developed small-for-size syndrome had inferior graft survival
to those who did not (P =.07). In conclusion, adult-to-adult LDLTs
were found to be feasible without affecting patient or graft survival.
Small-for-size syndrome developed more frequently in patients
with cirrhosis. Minimum GV in adult-to-adult LDLT should be 30%
less than the recipient's SLV in patients without cirrhosis, whereas
45% less was required in patients with cirrhosis.
Hepatology. 2003 Jul;38(1):258-66.
The management of ascites in cirrhosis: report
on the consensus conference of the International
Ascites Club.
Moore KP, Wong F, Gines P, Bernardi M, Ochs A, Salerno
F, Angeli P, Porayko M, Moreau R, Garcia-Tsao G, Jimenez W, Planas
R, Arroyo V.
Centre for Hepatology, Royal Free and University College Medical
School, UCL, London, United Kingdom. kmoore@rfc.ucl.ac.uk
Ascites is a common complication of cirrhosis, and heralds
a new phase of hepatic decompensation in the progression of the
cirrhotic process. The development of ascites carries a significant
worsening of the prognosis. It is important to diagnose noncirrhotic
causes of ascites such as malignancy, tuberculosis, and pancreatic
ascites since these occur with increased frequency in patients
with liver disease. The International Ascites Club, representing
the spectrum of clinical practice from North America to Europe,
have developed guidelines by consensus in the management of cirrhotic
ascites from the early ascitic stage to the stage of refractory
ascites. Mild to moderate ascites should be managed by modest
salt restriction and diuretic therapy with spironolactone or an
equivalent in the first instance. Diuretics should be added in
a stepwise fashion while maintaining sodium restriction. Gross
ascites should be treated with therapeutic paracentesis followed
by colloid volume expansion, and diuretic therapy. Refractory
ascites is managed by repeated large volume paracentesis or insertion
of a transjugular intrahepatic portosystemic stent shunt (TIPS).
Successful placement of TIPS results in improved renal function,
sodium excretion, and general well-being of the patient but without
proven survival benefits. Clinicians caring for these patients
should be aware of the potential complications of each treatment
modality and be prepared to discontinue diuretics or not proceed
with TIPS placement should complications or contraindications
develop. Liver transplantation should be considered for all ascitic
patients, and this should preferably be performed prior to the
development of renal dysfunction to prevent further compromise
of their prognosis.
Liver Transpl. 2003 Jun;9(6):539-46.
Recurrent primary biliary cirrhosis.
Neuberger J.
Liver Unit, Queen Elizabeth Hospital, Birmingham, United Kingdom.
J.M.Neuberger@bham.ac.uk
Liver transplantation remains the only effective treatment
for end-stage primary biliary cirrhosis (PBC). It appears now
well accepted that the disease recurs in the allograft. The diagnosis
of recurrent PBC is made on the basis of a consistent history
and demonstrating the histologic features of PBC on liver biopsy
and exclusion of other causes of bile duct damage.
Hepatogastroenterology. 2003 May-Jun;50(51):784-8.
Results of modified Sugiura operation in variceal
bleeding in cirrhotic and noncirrhotic patients.
Haciyanli M, Genc H, Halici H, Kumkumoglu Y, Gur OS, Ozturk
T.
Ataturk Training and Research Hospital, 2nd General Surgery Department,
Izmir, Turkey. mhaciyanli@hotmail.com
BACKGROUND/AIMS: Esophageal variceal bleeding is a major complication
of portal hypertension and the optimal therapeutic modality for
each individual patient differs. We reviewed the results of modified
Sugiura procedure in patients with variceal bleeding of esophagus.
METHODOLOGY: We retrospectively reviewed the charts of 13 patients
who were subjected to modified Sugiura procedure (transabdominal
esophagogastric devascularization + esophageal stapled transection
+ splenectomy) for bleeding esophageal varices between 1996 and
2001. Three patients disappeared from routine follow-up and were
excluded from the study. Survival, rebleeding and encephalopathy
were evaluated. RESULTS: The mean age was 46 (18-56). The etiology
of portal hypertension was cirrhosis of liver in six (60%) and
portal vein thrombosis in four (40%). One patient had Child-Pugh's
Class A, two had Class B and three had Class C cirrhosis. Previous
variceal bleeding were confirmed by endoscopy in all patients
who had recurrent variceal bleeding despite treatment with beta-blockers
(three patients) or endoscopic sclerotherapy +/- band ligation
(seven patients). Two were subjected to emergency surgery while
the remaining eight were operated on electively. No postoperative
mortality was seen. The bleeders were stopped immediately in the
emergent cases. During a mean follow-up of 27 (4-53) months, one
(10%) patient suffered from encephalopathy and one (10%) from
rebleeding at 20th and 28th months after the operation respectively.
Three (30%) patients with Child C cirrhosis died due to bleeding
(one) and hepatic failure (two) at 4, 25, and 28 months after
the surgery. The prognoses of other patients are well at the present
time. CONCLUSIONS: In our small number of patients, modified Sugiura
procedure was found to be a safe and effective procedure for urgent
and long-term control of bleeding varices in patients with portal
hypertension due to cirrhosis and noncirrhotic etiology. The outcomes
are encouraging in noncirrhotic patients and cirrhotic patients
with good liver functions.
Hepatogastroenterology. 2003 May-Jun;50(51):645-50.
Radiofrequency ablation for treatment of hepatocellular
carcinoma with cirrhosis.
Lo HW, Tsai YJ, Chen PH, Chen HY, Ker CG, Juan CC.
Division of Hepatology, Institute of Hepato-Gastroenterology,
Yuan's General Hospital, No. 162, Cheng Kung 1st Rd, Kaohsiung
80211, Taiwan.
BACKGROUND/AIMS: The majority of hepatocellular carcinoma patients
with cirrhosis are not candidates for surgical resection, and
local thermal therapy producing destruction of cancer cells was
one of the ideal options for treatment. Heat from radiofrequency
ablation is generated through agitation caused by an alternating
electrical current. The heat of radiofrequency energy results
in local cell coagulation and causes cellular ablation necrosis
of tumor tissue. METHODOLOGY: Eighteen cases of hepatocellular
carcinoma were treated with radiofrequency ablation in our institute.
We used a RFA 2000 generator (Boston Scientific Co, USA) with
LeVeen needle with the maximum diameter of 3.5 cm when the array
electrodes were fanned out. The indications for this method included;
i) normal prothrombin profile, ii) no ascites, iii) tumor can
be detected and approached by ultrasound, iv) tumor cannot be
resected or patient is not willing to take the operation. RESULTS:
No specific complication was noted during or after the procedure.
Only two cases needed more analgesics after the procedure. One
case was found with burning of the stomach serosa proved by laparoscopic
examination, in which radiofrequency ablation was performed to
the tumor located in the left lobe of the segment 3. Impedance
could not raise up completely in two cases with larger size tumor
more than 5 cm. The decreased levels of alpha-fetoprotein were
significant (P = 0.005) after radiofrequency ablation treatment.
Residual tumor was found in four cases (20%) in the follow-up
abdominal computed tomography scan. CONCLUSIONS: Radiofrequency
ablation resulted in a higher rate of complete necrosis of tumor
tissue and the complication rate was low as well. Therefore, we
believed that radiofrequency ablation is an ideal treatment modality
for most liver tumors, which cannot tolerate the conventional
surgical procedures.
World J Gastroenterol. 2003 May;9(5):1090-3.
A new technique of combined endoscopic sclerotherapy
and ligation for variceal bleeding.
Dhiman RK, Chawla YK.
Department of Hepatology, Postgraduate Institute of Medical Education
& Research, Chandigarh, India. rkpsdhiman@hotmail.com
AIM: To develop a technique of combined endoscopic sclerotherapy
and ligation (ESL) in which both techniques of endoscopic sclerotherapy
(ES) and endoscopic variceal ligation (EVL) can be optimally used.
METHODS: ESL was performed in 10 patients (age 46.4+/-7.9; 9 males,
1 female) with cirrhosis of liver using sclerotherapy needle and
Speedband, Superview multiple band ligater (Boston Scientific,
Microvasive, Watertown, MA). A single band was placed 5-10 cm
proximal to the gastro-esophageal junction over each varix from
proximal to distal margin, followed by intravariceal injection
of 1.5 % ethoxysclerol (4 ml each) 2 to 3 cm proximal to the gastroesophageal
junction on the ligated varices distal to deployed band. EVL was
then performed at the injection site. Similarly other varices
were also injected and ligated from distal to proximally. In the
subsequent sessions, ES alone was performed to sclerose small
varices at the gastroesophageal junction. RESULTS: ESL was successfully
performed in all patients. A median of 3 (ESL 1, ES 2) sessions
(ranged 1-4) were required to eradicate the varices in 9 (90 %)
of 10 patients. Recurrence of varices without bleed was seen in
1 patient during a mean follow-up of 10.3 months (ranged 6-15).
Two patients died of liver failure. None died of variceal bleeding.
None of the patients had procedure related complications. CONCLUSION:
ESL may be useful in the fast eradication of esophageal varices.
However, randomised controlled trials are required to find out
its relative efficacy and impact on variceal recurrence in comparison
to ES or EVL.
Hepatology. 2003 May;37(5):1147-53.
Randomized trial comparing albumin and saline
in the prevention of paracentesis-induced circulatory dysfunction
in cirrhotic patients with ascites.
Sola-Vera J, Minana J, Ricart E, Planella M, Gonzalez B,
Torras X, Rodriguez J, Such J, Pascual S, Soriano G, Perez-Mateo
M, Guarner C.
Liver Unit, Internal Medicine Department, Hospital General Universitario
de Alicante, Spain.
Paracentesis-induced circulatory dysfunction (PICD) is a recently
described complication that can be prevented with the administration
of plasma expanders. The aim of this study was to compare the
efficacy of saline versus albumin in the prevention of PICD. Patients
were randomized to receive albumin or saline after total paracentesis.
Patients readmitted as a consequence of a second episode of tense
ascites were treated with total paracentesis and the alternative
plasma expander. After randomization, 35 patients received saline
and 37 received albumin. Twenty-one patients were readmitted for
tense ascites and treated with the alternative expander. Significant
increases in plasma renin activity (PRA) were found 24 hours and
6 days after paracentesis when saline was used (baseline, 5.6
+/- 5.7; 24 hours, 7.6 +/- 6.9; 6 days, 8.5 +/- 8.0 ng x mL(-1).
hr(-1); P <.05 and P <.01 vs. baseline, respectively), whereas
no significant changes were observed with albumin. The incidence
of PICD was significantly higher in the saline group versus the
albumin group (33.3% vs. 11.4%, respectively; P =.03). However,
no significant differences were found when less than 6 L of ascitic
fluid was evacuated (6.7% vs. 5.6% in the saline and albumin groups,
respectively; P =.9). Similar results were observed when analyzing
patients who received 2 consecutive paracentesis (i.e., a significant
increase in PRA after saline [P <.01] without significant variations
after albumin). In conclusion, albumin is more effective than
saline in the prevention of PICD. Saline is a valid alternative
to albumin when less than 6 L of ascitic fluid is evacuated.
Ann Pharmacother. 2003 May;37(5):695-700.
Combined furosemide and human albumin treatment
for diuretic-resistant edema.
Elwell RJ, Spencer AP, Eisele G.
Department of Pharmacy Practice, Albany College of Pharmacy, Albany,
NY 12208-3492, USA. elwellr@acp.edu
OBJECTIVE: To evaluate the clinical usefulness of combined
furosemide and human albumin for the treatment of diuretic-resistant
edema in patients with nephrotic syndrome and cirrhosis. DATA
SOURCES: Clinical literature was accessed through MEDLINE (1966-May
2002). Key search terms included furosemide, albumin, human albumin
solution, nephrotic syndrome, and cirrhosis. DATA SYNTHESIS: Hypoalbuminemia,
edema, and ascites are often manifestations of nephrotic syndrome
and cirrhosis of the liver. Many patients with these conditions
are resistant to the effects of diuretics. The combination of
furosemide and human albumin solution is occasionally used in
these patients. An evaluation of published studies focusing on
combined furosemide and albumin in the management of nephrotic
syndrome and cirrhosis was conducted. CONCLUSIONS: Published studies
report conflicting results regarding the efficacy of combined
furosemide and albumin. Although it is difficult to generate firm
conclusions, it appears the combination may provide clinical benefits
for select patients. Given these findings, we believe that the
addition of albumin to enhance diuretic efficacy should be reserved
for patients with recalcitrant edema or ascites in whom diuretic
doses have been maximized and those with severe hypoalbuminemia.
Croat Med J. 2003 Apr;44(2):178-86.
Clinical and neurohumoral response to posture,
physical exercise, and ascites treatment in Child-Pugh C liver
cirrhosis: randomized prospective trial.
Degoricija V, Zjacic-Rotkvic V, Marout J, Sefer S, Troskot
B.
Department of Medicine, Sisters of Mercy University Hospital,
Vinogradska cesta 29, 10000 Zagreb, Croatia. vesna.degoricija@zg.tel.hr
AIM: To assess clinical and neurohumoral response to posture,
physical exercise, and ascites treatment in patients with Child-Pugh
C liver cirrhosis and tense ascites. METHOD: Fifty patients with
Child-Pugh C liver cirrhosis and tense ascites were randomly allocated
into 5 groups. Thirty patients were treated with paracentesis
of 6 L of acites paralleled by plasma volume expansion with 200
mL of 20% low sodium albumin (10 patients), 600 mL fresh frozen
plasma (10 patients), or 900 mL solution of synthetic gelatine
(10 patients), ie, doses with comparable oncotic power, and bed
rest for 24 h before and after the procedure. They were compared
with 10 patients treated with paracentesis of 6 L of ascites without
plasma volume expansion and no bed rest, and 10 patients treated
with 40 mg of furosemide IV daily and no bed rest. Mean arterial
pressure, heart rate, body weight loss, urine flow rate, creatinine
clearance, plasma renin activity, plasma aldosterone concentration,
and plasma atrial natriuretic peptide (ANP) were measured before
the procedure and 6 hours, 2, 3, and 6 days after the procedure.
RESULTS: Diuretic treatment and paracentesis of 6 L of ascites
without plasma volume expansion and no bed rest 24 h before and
after the procedure were associated with significant hypotension
(p<0.01) during 6 days of the trial, tachycardia (p<0.01)
on day 1 and 2 (p=0.012), lower total body weight loss (p=0.007),
increase in plasma renin activity 6 hours after the beginning
of the study (p=0.025) and on day 6 (p=0.024), increase in plasma
aldosterone concentration on day 6 (p=0.030), no significant change
in plasma ANP levels, and decrease in creatinine clearance on
day 6 (p=0.046). Albumin was superior to the other plasma expanders.
Comparison between groups treated with plasma volume expansion
did not show significant differences in measured parameters at
any time during the study. The differences were found in the amount
of needed volume of each substitute, daily sodium balance on day
1 of the trial, increase in plasma aldosterone concentration in
bed rest-paracentesis-polygeline group on day 6, and the increase
in plasma ANP on day 1 (p=0.077), which was proportional to the
amount of infused volume. CONCLUSION: Therapeutic paracentesis
of 6 L of ascites, bed rest 24 h before and after the procedure,
and intravenous substitution of volume with albumin, fresh frozen
plasma, and solution of synthetic gelatine were safe, rapid, and
effective treatments, provided that intravascular volume was substituted
simultaneously.
Presse Med. 2003 Apr 26;32(15):704-10.
[Regression of hepatic fibrosis physiopathological
aspects and clinical reality]
[Article in French]
Bedossa P, Paradis V.
Service d'anatomie pathologique, CNRS ESA 8067, Hopital Bicetre
Le Kremlin Bicetre (94). pbedossa@teaser.fr
MANAGING THE RESPONSIBLE AGENT: Hepatic fibrosis with its end-point,
cirrhosis, are the principle complications responsible for morbidity
and mortality in chronic liver diseases. It is therefore important
to address the question of whether these lesions can disappear,
once installed in the liver. Regression can only occur when the
agent responsible for the fibrosis (virus, alcohol, poison, iron,
autoantibodies, etc) is eradicated or controlled. THE FORMS OF
REGRESSION: Once the agent controlled, regression of fibrosis
can either be spontaneous, a rare situation, although some bona
fide cases of fibrosis or even cirrhosis reversion have been reported
in the literature, or assisted by specific therapy. It is therefore
necessary to take into consideration the development of new treatments
based on enhanced knowledge of the mechanisms of fibrosis. THE
ACTIVITY AND EFFICACY OF TREATMENTS: These treatments target one
of the three following mechanisms: the blockade of hepatic stellate
cell activation, enzymatic digestion of fibrous tissue and stimulation
of liver cell regeneration. Although these treatments have shown
efficacy on experimental models of fibrosis, to date, there are
no published results formally confirming the efficacy and safety
of these treatments in man.
Hepatogastroenterology. 2003 Mar-Apr;50(50):504-6.
The effect of beta-blocker on intractable ascites
in cirrhotic patients undergoing hepatectomy for hepatocellular
carcinoma.
Kondo M, Nagano H, Sakon M, Hayashi S, Okami J, Dono K,
Umeshita K, Nakamori S, Wakasa K, Monden M.
Department of Surgery and Clinical Oncology, Graduate School of
Medicine, Osaka University, 2-2, Yamadaoka, Suita City, Osaka,
565-0871, Japan.
BACKGROUND/AIMS: Intractable ascites is one of the serious
complications after hepatectomy. Only little is known about their
effect on postoperative ascites in patients with liver cirrhosis
although beta-blockers have been used for cirrhotic complications
including ascites. METHODOLOGY: Here, we report five cases of
intractable ascites after hepatectomy, which were treated by propranolol
(1 mg/kg/body). RESULTS: In three patients, plasma renin activity
and aldosterone concentrations were markedly increased before
propranolol administration, but fell to normal levels thereafter.
Ascites subsided in all subjects except one, who developed cardiac
dysfunction. CONCLUSIONS: Beta-blockers might be a promising drug
for intractable ascites in cirrhotic patients undergoing hepatectomy.
Autoimmun Rev. 2003 Jan;2(1):1-7.
Liver transplantation for primary biliary cirrhosis.
Neuberger J.
Liver Unit, Queen Elizabeth Hospital, Birmingham B15 2TH, UK.
j.m.neuberger@bham.ac.uk
Liver transplantation is now the accepted treatment for patients
with end-stage disease or intractable symptoms. The success rate
is high. Those grafted for PBC are at greater risk of developing
acute and chronic rejection and are less likely to be weaned from
immunosuppression. Following transplantation, AMA persist and
histological features of PBC may be seen in the allograft, in
up to 50% by 10 years.
Hepatology. 2003 Apr;37(4):887-92.
A randomized controlled trial of ursodeoxycholic
acid in patients with alcohol-induced
cirrhosis and jaundice.
Pelletier G, Roulot D, Davion T, Masliah C, Causse X, Oberti F,
Raabe JJ, Van Lemmens C, Labadie H, Serfaty L; URSOMAF Group.
Department of Gastroenterology of Hopital Bicetre, Assistance
Publique-Hoopitaux de Paris, Paris, France.
The aim of our multicenter study was to assess the efficacy
of ursodeoxycholic acid (UDCA) on the survival of patients with
alcohol-induced cirrhosis and jaundice. We included patients with
histologically proven alcohol-induced cirrhosis and serum bilirubin
>50 micromol/L. After randomization, patients received either
UDCA (13-15 mg/kg/d) or a placebo for 6 months. Two hundred twenty-six
patients (113 in each group) were included in 24 centers. There
were 139 men and 87 women, mean age of 50.3 years. Seventy-four
percent had associated alcohol-induced hepatitis, and 24% received
a corticosteroid therapy. At inclusion, the 2 groups were comparable
for the main clinical and biologic parameters, but serum bilirubin
was higher in the UDCA group than in the placebo group (163 micromol/L
vs. 145 micromol/L, P <.03). The percentage of patients lost
at follow-up or who resumed their alcoholism during the study
was comparable in the 2 groups. During the study, 55 patients
died, 35 in the UDCA group and 20 in the placebo group. In the
intention to treat analysis, the probability of survival at 6
months (Kaplan-Meier method) was lower in the UDCA than in the
P group (69% vs. 82%, respectively; P =.04, log-rank test). After
adjustment on the bilirubin level at entry (Cox model), the independent
predictive value of the treatment group did not reach the statistical
level (RR = 1.64, CI 0.85-2.85; P =.077). In conclusion, UDCA
administered at the dose recommended in primary biliary cirrhosis
has no beneficial effect on the 6-month survival of patients with
severe alcohol-induced cirrhosis. An inappropriate dosage of UDCA
cannot be excluded as an explanation for the lack of therapeutic
benefit.
Am J Gastroenterol. 2002 Oct;97(10):2647-50.
Results of long-term ursodiol treatment for patients
with primary biliary cirrhosis.
Jorgensen R, Angulo P, Dickson ER, Lindor KD.
Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester,
Minnesota 55905, USA.
OBJECTIVE: When ursodeoxycholic acid (UDCA) is used for the
treatment of primary biliary cirrhosis, it has been associated
with biochemical improvement, histological stability, reduced
risk of esophageal varices, and increased survival free of transplantation.
There is limited information available about the long-term outcome
of these patients with primary biliary cirrhosis on UDCA treatment.
To address this, we reviewed the long-term results from patients
enrolled in our original randomized study with up to 12 yr of
follow-up. METHODS: From April 1988 to March 1992, a total of
180 patients were enrolled into a randomized, controlled trial
evaluating UDCA (n = 89) versus placebo (n = 91). When the randomized
portion of the study concluded in May 1992, patients were switched
to active medication and followed for up to an additional 8 yr.
RESULTS: Twenty-eight patients originally assigned to UDCA and
42 patients originally assigned to placebo have died or undergone
transplantation. The patients who died or were transplanted were
more histologically advanced at entry (p < 0.001). Seventy-six
of the remaining 110 patients return for regular follow-up; mailed
questionnaires were returned by an additional 25 patients, and
nine patients have been lost to follow-up. Twenty-two of the 76
patients we follow have normal liver tests (ALP, bilirubin, and
AST). Patients with normal liver tests had significantly lower
levels of ALP and AST at baseline (p < 0.05), but did not differ
in histological stage or total bilirubin from those with persistently
abnormal tests. CONCLUSIONS: UDCA appears to be of most benefit
when instituted in early stage disease. Although a substantial
percentage of patients will achieve biochemical normalization
on UDCA alone, there is a continued need for therapeutic options
for others who have less complete biochemical responses.
Am J Gastroenterol. 2003 Jan;98(1):205-8.
Efficacy of colchicine in patients with primary
biliary cirrhosis poorly responsive to ursodiol and methotrexate.
Lee YM, Kaplan MM.
Division of Gastroenterology, New England Medical Center, Tufts
University School of Medicine, and the Tupper Research Institute,
Boston, Massachusetts 02111, USA.
OBJECTIVE: Approximately 20-30% of patients with primary biliary
cirrhosis (PBC) respond fully to treatment with ursodeoxycholic
acid (UDCA). The rest have progressive disease and eventually
develop cirrhosis and liver failure. More effective treatment
is needed. Methotrexate improved biochemical tests of liver function
and liver histology in patients with PBC who had failed to respond
to UDCA in one report and induced sustained biochemical and histological
remission in another. The role of colchicine in PBC is unclear.
We describe three patients with symptomatic PBC who responded
very well to the addition of colchicine after they had failed
to respond to UDCA alone and in combination with methotrexate.
We suggest that colchicine should be tried in PBC patients who
clearly fail to respond to UDCA. METHODS: Three patients with
symptomatic biopsy-proven, antimitochondrial antibody-positive
PBC failed to respond to UDCA and then to the addition of methotrexate.
Colchicine was eventually added to the regimen. Symptoms, biochemical
tests of liver function, and percutaneous liver biopsies were
done at baseline, after treatment with UDCA, UDCA plus methotrexate,
and UDCA plus methotrexate plus colchicine. RESULTS: All three
patients responded after colchicine was added to UDCA and methotrexate.
Symptoms, biochemical tests of liver function, and liver histology
improved in all, and blood tests normalized in two. CONCLUSIONS:
Colchicine may be effective treatment in some symptomatic patients
with PBC who respond incompletely to UDCA alone or in combination
with methotrexate. Colchicine may be tried in such patients.
Am J Gastroenterol. 2003 Jan;98(1):187-93.
Methotrexate therapy for primary biliary cirrhosis.
Bach N, Bodian C, Bodenheimer H, Croen E, Berk PD, Thung SN, Lindor
KD, Therneau T, Schaffner F.
Department of Medicine, Mount Sinai School of Medicine, New York,
New York 10029, USA.
OBJECTIVE: Preliminary data suggested possible benefits of
methotrexate in primary biliary cirrhosis. We assessed the effectiveness
of methotrexate use in primary biliary cirrhosis and its tolerance
in patients with this disease. METHODS: A total of 110 primary
biliary cirrhosis patients began methotrexate 15 mg/wk; for most,
ursodeoxycholic acid was added during the study. We analyzed data
from patients completing 5 yr of treatment with methotrexate to
assess its effect on biochemical and histologic parameters after
5 yr of therapy. Based on an intent to treat analysis, we also
compared survival of our patients (n = 110) with that of patients
in a previously published, placebo-controlled trial of ursodeoxycholic
acid (n = 180). RESULTS: Only half of the study group completed
5 yr of methotrexate therapy. Therapy did not prevent progression
of disease, as indicated by a rising Mayo risk score. Portal fibrosis
tended to remain the same. Methotrexate did not diminish the risk
of death or liver transplantation when compared with ursodeoxycholic
acid or placebo; however, ursodeoxycholic acid use decreased the
risk of death or transplant (p = 0.006). CONCLUSIONS: Methotrexate
is not well tolerated in primary biliary cirrhosis. The toxicity
of methotrexate and its inability to prevent complications of
progressive liver disease or improve survival and the need for
liver transplantation limits its utility. The benefits of ursodeoxycholic
acid were again confirmed.
Eur J Gastroenterol Hepatol. 2002 Dec;14(12):1369-76.
The influence of sulindac on patients with primary
biliary cirrhosis that responds incompletely to ursodeoxycholic
acid: a pilot study.
Leuschner M, Holtmeier J, Ackermann H, Leuschner U.
Medical Clinic II, Johann Wolfgang Goethe Universitat, Frankfurt
am Main, Germany.
OBJECTIVES: In 30% of patients with primary biliary cirrhosis
(PBC) ursodeoxycholic acid (UDCA) causes full biochemical normalization,
while 70% are incomplete responders. The only differences between
the two groups are the significantly higher cholestasis indices
in the incomplete responders. In these patients we investigated
whether the strongly choleretic sulindac together with UDCA is
superior to UDCA monotherapy. DESIGN AND METHODS: Twenty-three
patients with PBC incompletely responding to UDCA monotherapy
were entered in the open label study for 12 months. Eleven patients
(stage II, seven; III, two; and IV, two) received UDCA (10-15
mg/kg/day) plus sulindac (100-300 mg/day) (Group I). Twelve patients
(stage I, six; II, four; III, one; and IV, one) were treated with
UDCA alone (Group II). Liver biochemistry, analysis of antimitochondrial,
antinuclear, smooth muscle, and liver-kidney-microsomal antibodies,
ultrasonography and gastroscopy were done in regular intervals.
RESULTS: In Group I all liver indices, IgG, IgM and IgA significantly
improved although pretreatment data and stages of the disease
tended to be higher than in Group II. In five patients of Group
I liver histology improved slightly. Sulindac was well tolerated.
The biochemical indices did not further improve on UDCA monotherapy.
CONCLUSIONS: Sulindac in combination with UDCA further improves
liver biochemistries in patients with PBC who responded incompletely
to UDCA alone.
Eur J Gastroenterol Hepatol. 2003 Jan;15(1):7-14.
Adult-to-adult living donor liver transplant:
UK experience.
Williams RS, Alisa AA, Karani JB, Muiesan P, Rela SM, Heaton ND.
Liver Unit Cromwell Hospital, University College London Hospitals,
London, UK. roger.williams@ucl.ac.uk
BACKGROUND: Adult-to-adult living donor liver transplantation
(ALDLT) is being adopted widely in the USA and mainland Europe,
fueled by the increasing waiting lists for cadaver organs. The
present report describes the first UK experience with the procedure
in patients from overseas who have the lowest priority for cadaver
organ allocation. METHODS: The 16 patients seen over the period
November 1998 to March 2002 had end-stage cirrhosis from chronic
hepatitis C virus (HCV) or hepatitis B virus (HBV) infection (13
cases), with single instances of cryptogenic cirrhosis, secondary
biliary cirrhosis and alcoholic liver disease. Grafts were left
lobe in the first two recipients and right lobe in the subsequent
14 recipients, donated by nine sons/daughters and seven brothers/sisters.
RESULTS: Twelve of the 16 recipients did well. The four recipients
who died had recurrent sepsis; two of these died following hepatic
arterial occlusion, and in three major surgical factors were present
before transplantation. Serial computed tomography (CT) measurements
in the survivors showed regeneration of the grafted lobe with
final volumes reaching in each case the calculated standard liver
volume for body size. In the donors, liver function tests had
returned to normal by day 7-14, with rapid regeneration of the
remaining lobe, although the final size attained that estimated
before donation in only four donors. CONCLUSIONS: ALDLT, although
requiring considerable facilities and organization, can give good
results for both recipient and donor. As with cadaver grafts,
outcome in the recipient if the larger right lobe is used is dependent
on surgical risk factors and the severity of clinical decompensation
before transplantation. Measures to ensure the safety of the donors
remain the main concern. Copyright 2003 Lippincott Williams &
Wilkins
Hepatology. 2003 May;37(5):1147-53.
Randomized trial comparing albumin and saline
in the prevention of paracentesis-induced circulatory dysfunction
in cirrhotic patients with ascites.
Sola-Vera J, Minana J, Ricart E, Planella M, Gonzalez B, Torras
X, Rodriguez J, Such J, Pascual S, Soriano G, Perez-Mateo M, Guarner
C.
Liver Unit, Internal Medicine Department, Hospital General Universitario
de Alicante, Spain.
Paracentesis-induced circulatory dysfunction (PICD) is a recently
described complication that can be prevented with the administration
of plasma expanders. The aim of this study was to compare the
efficacy of saline versus albumin in the prevention of PICD. Patients
were randomized to receive albumin or saline after total paracentesis.
Patients readmitted as a consequence of a second episode of tense
ascites were treated with total paracentesis and the alternative
plasma expander. After randomization, 35 patients received saline
and 37 received albumin. Twenty-one patients were readmitted for
tense ascites and treated with the alternative expander. Significant
increases in plasma renin activity (PRA) were found 24 hours and
6 days after paracentesis when saline was used (baseline, 5.6
+/- 5.7; 24 hours, 7.6 +/- 6.9; 6 days, 8.5 +/- 8.0 ng x mL(-1).
hr(-1); P <.05 and P <.01 vs. baseline, respectively), whereas
no significant changes were observed with albumin. The incidence
of PICD was significantly higher in the saline group versus the
albumin group (33.3% vs. 11.4%, respectively; P =.03). However,
no significant differences were found when less than 6 L of ascitic
fluid was evacuated (6.7% vs. 5.6% in the saline and albumin groups,
respectively; P =.9). Similar results were observed when analyzing
patients who received 2 consecutive paracentesis (i.e., a significant
increase in PRA after saline [P <.01] without significant variations
after albumin). In conclusion, albumin is more effective than
saline in the prevention of PICD. Saline is a valid alternative
to albumin when less than 6 L of ascitic fluid is evacuated.
Rom J Gastroenterol. 2003 Mar;12(1):25-30.
Long term effects of propranolol on portal pressure
in cirrhotic patients.
Orban-Schiopu AM, Popescu CR.
Department of Internal Medicine. University Hospital Elias, Bd.
Marasti no.17, 71322 Bucharest, Romania.
Bleeding from varices is a very serious complication in cirrhotic
patients, with a mean mortality rate around 30 %. If the portal
vein pressure is decreased by pharmacological therapy the varices
will not bleed and progressively decrease in size. The portal
hypertension in cirrhotic patients develops as a consequence of
two mechanisms: the increase of portal inflow and the increase
of intrahepatic resistance. The aim of our study was to find out
if propranolol can prevent the bleeding from esophageal varices
and if it acts by reducing the portal inflow due to splanchnic
vasodilatation. The study was initiated in 53 patients with portal
hypertension, of whom 14 were withdrawn because of adverse effects
of propranolol. Abdominal ultrasonography and Doppler of portal
vein system were performed in all subjects. The ultrasonographic
parameters were measured before and after a 3-year treatment with
propranolol. The patients also underwent endoscopy for evaluation
of esophageal varices; the endoscopy was repeated at the end-point
of treatment. We noted that propranolol reduced the portal blood
inflow and the size of esophageal varices, and that the incidence
of hemorrhages by variceal rupture was very low in these patients.
Dig Dis Sci. 2003 Jan;48(1):179-86
Effects of orthotopic liver transplantation on
vasoactive systems and renal function in patients with advanced
liver cirrhosis.
Cassinello C, Moreno E, Gozalo A, Ortuno B, Cuenca B, Solis-Herruzo
JA.
Department of Gastroenterology, Hospital Universitario 12 de Octubre,
28041 Madrid, Spain.
The effects of Orthotopic liver transplantation (OLT) on renal
function and major vasoactive factors was assessed in end-stage
cirrhotic patients. Renal function, mean arterial pressure, and
plasma vasoactive hormones were measured In 22 cirrhotic patients
with refractory ascites before and after OLT. Before OLT, mean
arterial pressure, glomerular filtration rate, free water clearance,
and fractional sodium excretion serum sodium levels were decreased.
In addition, serum creatinine and plasma levels of vasoactive
factors were increased. Ten of these patients fulfilled criteria
of hepatorenal syndrome (HRS). Nine to 12 months after transplantation,
renal function had improved and plasma levels of vasoactive factors
had decreased significantly in all patients, including those with
HRS. However, glomerular filtration rate remained subnormal and
plasma endothelin-1 levels and plasma renin activity remained
increased in most of them. In conclusion, OLT improves renal function
in patients with end-stage liver cirrhosis, including those with
HRS. However, renal function remains subnormal in most of these
patients.
Rev Med Chil. 2002 Dec;130(12):1343-8.
[Laparoscopic and classic cholecystectomy in patients
with liver cirrhosis]
[Article in Spanish]
Poniachik J, Castro S, Madrid AM, Quera R, Amat J, Smok G, Cumsille
M, Brahm J.
Seccion de Gastroenterologia, Departamento de Cirugia, Instituto
de Anatomia Patologica y Departamento de Salud Publica, Hospital
Clinico Universidad de Chile, Santos Dumont 999. jponiach@ns.hospital.uchile.cl
BACKGROUND: The prevalence of gallstones is increased in patients
with cirrhosis. However the presence of cirrhosis has been generally
considered a relative contraindication to cholecystectomy. AIM:
To investigate the complications and the outcomes of laparoscopic
and open cholecystectomy in patients with cirrhosis. PATIENTS
AND METHODS: Sixty seven patients with gallstones with well-documented
cirrhosis undergoing cholecystectomy (laparoscopic cholecystectomy
(LC) in 35 and open cholecystectomy (OC) in 32), were studied.
The mean age was 57.7 + 10.3 years for LC and 58.9 + 11.6 years
for OC. In the LC group, 26 were classified as Child-Pugh class
A, 8 as Child's B class and 1 as Child's class C. In the OC group,
12 were classified as Child's class A, 15 as Child's B and 5 as
Child's C. RESULTS: Complications occurred in 4 of 35 (12.3%)
LC patients (1 patients was Child A and 3 were B). In the OC group
14 of 32 patients had complications (4 Child A, 7 B and 3 C, 43.7%
p < 0.05 as compared with LC group). Three patients in the
OC group died (9.4%). Mean hospital stay was 2.8 + 1.9 and 13
+ 12 days in LC and OC patients, respectively (p < 0.05). CONCLUSIONS:
LC has a lower rate of complications than OC and is a reasonable
option for Child's class A and B patients with cirrhosis and gallstones.
Ugeskr Laeger. 2003 Jan 27;165(5):439-42.
[Transjugular intrahepatic portosystemic shunt
(TIPS) for the treatment of complications of portal hypertension
in patients with liver cirrhosis]
[Article in Danish]
Gronbaek H, Astrup LB, Nielsen DT, Vilstrup H.
Arhus Universitetshospital, Arhus Kommunehospital, Medicinsk Afdeling
V og Radiologisk Afdeling R. henning.gronbaek@dadlnet.dk
Portal hypertension is a main cause for the development of
esophago-gastric varices, ascites and hepatic nephropathy in liver
cirrhosis. Reduction of portal pressure by a transjugular intrahepatic
portosystemic shunt (TIPS) procedure has been possible for the
last decade. The treatment reduces the risk for variceal bleeding,
reduces ascites formation and may improve renal function in hepatic
nephropathy. Improved survival, however, has not yet been documented.
Complications comprise procedure related events (puncture of liver
capsule, bleeding, infection, hemolysis with mortality 1-5%),
shunt stenosis (30-80% during the first year but reversible),
and encephalopathy (30% intermittent, 10% chronic). Indications
for the procedure are primarily variceal bleeding resistant to
conventional pharmacologic and endoscopic treatment. Absolute
and relative contraindications are severe hepatic failure, a history
of hepatic encephalopathy, infections, respiratory failure, and
non-hepatic renal insufficiency.
Zhongguo Zhong Xi Yi Jie He Za Zhi. 2001 Nov;21(11):813-5.
[Clinical and experimental study on anti-liver
fibrosis effect of xuelong granule]
[Article in Chinese]
Li ZZ, Wang X, Sui ZY.
Jining Municipal Infectious Diseases Hospital, Shandong 272031.
OBJECTIVE: To study the clinical effect and mechanism of Xuelong
Granule (XLG) in antiliver fibrosis. METHODS: Ninety-eight patients
with liver cirrhosis were divided into 2 groups randomly. The
58 Patients in the treated group were treated by XLG and the 40
patients in the control group were treated by Shenchai Granule
for 3 months. Levels of serum hyaluronic acid (HA) and laminin
(LN), and pathological changes of liver tissues were observed
before and after treatment. In experimental study on model rats,
the liver tissue content of hydroxyproline and pathological changes
under light and electron microscope were observed. RESULTS: The
total effective rate in the treated group was 72.4%, that in the
control group was 40.0%, there was significant difference between
the two groups (P < 0.01). The level of serum HA and LN in
the treated group declined markedly after treatment, and pathological
examination of 8 cases showed the fibrous tissues reduced obviously.
Experimental study showed marked reduction of hydroxyproline content
and significant lowering of fibrous tissue proliferation, both
under light and electron microscope, in liver of model rats after
XLG treatment. CONCLUSION: XLG has a definite effect in anti-liver
fibrosis.
Hepatology. 2003 Feb;37(2):378-84.
Low doses of isosorbide mononitrate attenuate
the postprandial increase in portal pressure in
patients with cirrhosis.
Bellis L, Berzigotti A, Abraldes JG, Moitinho E, Garcia-Pagan
JC, Bosch J, Rodes J.
Hepatic Hemodynamic Laboratory, Liver Unit, IMD, Hospital Clinic,
Barcelona, Spain.
Postprandial hyperemia is associated with a significant increase
in portal pressure in cirrhosis, which may contribute to progressive
dilation and rupture of gastroesophageal varices. In cirrhosis,
an insufficient hepatic production of nitric oxide (NO) may impair
the expected hepatic vasodilatory response to increased blood
flow, further exaggerating the postprandial increase in portal
pressure. This study was aimed at investigating whether low doses
of an oral NO donor might counteract the postprandial peak in
portal pressure. Twenty-three portal hypertensive cirrhotics,
8 of them under propranolol therapy, were randomized to receive
orally 5-isosorbide mononitrate (ISMN; 10 mg; n = 11) or placebo
(n = 12) and a standard liquid meal 15 minutes later. Hepatic
venous pressure gradient (HVPG), mean arterial pressure (MAP),
and hepatic blood flow (HBF) were measured at baseline and 15,
30, and 45 minutes after a meal. ISMN significantly attenuated
the postprandial increase in portal pressure as compared with
placebo (peak HVPG increase: 2.4 +/- 1.4 mm Hg vs. 5.2 +/- 2.1
mm Hg, P =.002). Percentual increases in HBF were similar in both
groups. MAP decreased slightly in ISMN group (-7.5% +/-.5%; P
<.01 vs. baseline). These effects were also observed in patients
on chronic propranolol therapy. In conclusion, hepatic NO supplementation
by low doses of ISMN effectively reduces the postprandial increase
of portal pressure in cirrhosis, with only a mild effect on arterial
pressure. The same was observed in patients receiving propranolol.
Our results suggest that therapeutic strategies based on selective
hepatic NO delivery may improve the treatment of portal hypertension.
Hepatology. 2003 Feb;37(2):359-65.
Nadolol plus spironolactone in the prophylaxis
of first variceal bleed in nonascitic cirrhotic patients: A preliminary
study.
Abecasis R, Kravetz D, Fassio E, Ameigeiras B, Garcia D, Isla
R, Landeira G, Dominguez N, Romero G, Argonz J, Terg R.
Liver Unit, Hospital de Gastroenterologia B. Udaondo, Buenos Aires,
Argentina. raquelabecasisabril@hotmail.com
Treatment with beta-blockers fails to decrease portal pressure
in nearly 40% of cirrhotic patients. Recent studies have suggested
that treatment with spironolactone reduces pressure and flow in
the portal and variceal systems. This trial was designed to assess
if nadolol plus spironolactone is more effective than nadolol
alone to prevent the first variceal bleeding. One hundred patients
with medium and large varices who had never bled and were without
ascites were included in a prospective, randomized, multicenter,
double-blind, placebo-controlled trial. The patients were randomized
into 2 groups: 51 received nadolol plus placebo (N + P) and 49
received nadolol plus spironolactone 100 mg/d (N + S). Hepatic
venous pressure gradient (HVPG) and activity of the renin-aldosterone
system (plasma renin activity/plasma aldosterone levels) were
measured in 24 patients. There were no significant differences
in the appearance of variceal bleeding and ascites between groups
at a mean follow-up of 22 +/- 16 months. However, analyzing both
complications together, the incidence was significantly higher
in the N + P group than in the N + S group (39% vs. 20%; P <.04).
Clinical ascites was also higher in patients in the N + P group
than in the N + S group (21% vs. 6%; P <.04). Significant increases
in plasma renin activity and plasma aldosterone levels were only
observed in patients in the N + S group (P <.01). The cumulative
probabilities of remaining free of bleeding and ascites were similar
in both groups after 70 months of follow-up. In conclusion, these
results suggest that nadolol plus spironolactone does not increase
the efficacy of nadolol alone in the prophylaxis of the first
variceal bleeding. However, when bleeding and ascites were considered
together, the combined therapy effectively reduced the incidence
of both portal-hypertensive complications.
Khirurgiia (Sofiia). 2002;58(1):8-10.
[Hepatic resections for hepatocellular carcinoma
and cirrhosis]
[Article in Bulgarian]
Frangov T, Gaidarski R, Vasilev S, Mladenov L.
Liver resection in a patient with cirrhosis carries increased
risk. The purposes of this study were to review the results of
cirrhotic liver resection in the past decade and to propose strategies
for low morbidity and mortality. From January 1991 to December
2000 73 patients with primary liver cancer (PLC) were operated
and identified in a retrospective database. Twenty five (34%)
patients had underlying cirrhosis: 14--Child A and 11--Child B.
There were 18 male and 7 female with mean age 60.9 +/- 9.2 (from
44 to 78). There were 16 (64%) resections: 11--stage Child A and
5--stage Child B. Major resections were 7 and minor--9. Eight
patients received hemotransfusion--mean 939.13 ml (370-2000 ml).
Four patients (25%) died of the hepatic resection--by the 30-th
day. Seven patients had postoperative complications. 4 patients
developed liver failure. Major resections had 42.86% mortality,
minor resections--11.11%. Hepatic resection is potentially curative
therapy for HCC and cirrhosis especially in Child A. Child B produce
high rate of postoperative morbidity and mortality.
Taehan Kan Hakhoe Chi. 2002 Mar;8(1):52-60.
[Efficacy and safety of large volume paracentesis
in cirrhotic patients with spontaneous bacterial peritonitis:
a randomized prospective study]
[Article in Korean]
Choi CH, Han KH, Kim do Y, Cho JH, Cheong JY, Song KH, Chon CY,
Moon YM.
Department of Internal Medicine, Gastroenterology division, Yonsei
University College of Medicine, Seoul, Korea. gihankhys@yumc.yonsei.ac.kr
BACKGROUND/AIMS: Large volume paracentesis (LVP) associated
with plasma volume expansion is known to be an effective and safe
therapy for tense or refractory ascites in cirrhosis. Spontaneous
bacterial peritonitis (SBP) is one of the frequent infections
in patients with cirrhosis. We conducted a study to assess the
efficacy and safety of large volume paracentesis in cirrhotic
patients with SBP. METHODS: We randomly assigned 40 patients with
cirrhosis and SBP to either treatment with LVP (21 patients) or
general management (19 patients). LVP was defined as drainage
of ascitic fluid of more than 4 liters in a single tap or loss
of shifting dullness after paracentesis. LVP was performed within
48 hours after the diagnosis of SBP in the LVP group. Cefotaxime
was given daily in doses that varied according to the serum creatinine
level in both groups. Albumin was given at a dose of 6-8 g per
1 liter of removed ascites in the LVP group. RESULTS: After seven
days of treatments, the blood chemistry test, and WBC (PMN) counts
and protein concentration in the ascitic fluid were not different
between the two groups. Among them, the WBC (PMN) counts were
decreased significantly in both groups and protein concentrations
tended to increase. Durations of abdominal tenderness and pain
were shorter in the LVP group but the differences were statistically
not significant. Admission periods, resolution rates of SBP after
seven days of treatment, complication rates and in-hospital mortality
rates were not different between the two groups. CONCLUSIONS:
The two treatment methods demonstrated almost the same effectiveness
and safety. The symptoms were improved slightly faster in the
LVP group. We concluded that large volume paracentesis is not
an absolute contraindication and can be a tolerable and safe therapy
in some selected cirrhotic patients with tense ascites and SBP.
Zhonghua Yi Xue Za Zhi. 2002 Sep 10;82(17):1157-9.
[The randomized controlled trial of isosorbide
mononitrate plus propranolol compared with propranolol alone for
the prevention of variceal rebleeding]
[Article in Chinese]
Zhang Q, Yuan R, Wang H.
Gastroenterology Department, The Branch of Shanghai First People's
Hospital. Shanghai 200081, China.
OBJECTIVE: The aim of this study was to test the effectiveness
of isosorbide-5-mononitrate (IM) as an adjunct to propranolol
(PR) in the prevention of variceal rebleeding. METHODS: Seventy-six
cirrhotic patients with variceal bleeding were randomly assigned
to treatment with PR + IM (34 patients) or PR alone (32 patients).
RESULTS: Seven patients in the PR + IM group and 13 in the PR
group had rebleeding during the 1 year after randomization. The
actuarial probability of rebleeding 1 years after randomization
was lower in the PR + IM group but the difference was not significant
(P = 0.09). However, by adding an additional 8 months of follow-up,
the decrease in the risk of rebleeding reached statistical significance
(P = 0.05). No significant difference was found in rebleeding
index and survival. The multivariate Cox analysis indicated both
treatment (P = 0.04), severity of liver disease (P = 0.03) and
age (P = 0.045) were factors predictive of rebleeding and second,
that PR + MI reduced the risk of rebleeding by half (relative
risk: 0.54). CONCLUSION: These results suggest that the addition
of IM improves the efficacy of PR alone in the prevention of variceal
rebleeding in cirrhotic patients. However no beneficial effects
were observed on other parameters reflecting the efficacy of treatment.
Int J Artif Organs. 2002 Oct;25(10):935-8.
Clinical outcome of orthotopic liver transplantation.
Berlakovich GA.
g.berlakovich@akh-wien.ac.at
Orthotopic liver transplantation (OLT) has become a standard
procedure for end-stage cirrhosis. The purpose of this anlysis
is to give a brief overview on the clinical outcome of OLT. According
to a current survey of primary indications for liver transplantation
in Europe, virus-induced cirrhosis represents the largest proportion
with 25%. The next frequent indication is alcoholic cirrhosis
with 19%. Cholestatic diseases amount to 13%, malignancy in cirrhosis
10%, and acute hepatic failure 10%. The outcome of these main
indications will be discussed and critical considerations pointed
out. Patient survival rates demonstrate for cirrhosis at 1-and
5-year about 80% and 70%, respectively. In acute hepatic failure,
more patients are lost in the perioperative period. Not surprisingly,
patients transplanted for malignancy show decreased long-term
survival. Considering an average of 5-year survival in patients
with end-stage liver disease of 20% or less, excellent patient
survival can be achieved by liver transplantation.
Int J Artif Organs. 2002 Oct;25(10):918-22.
Influence of hydroxy ethyl starch infusion on
serum bilirubin levels in cirrhotic patients treated with artificial
liver support.
Kramer L, Bauer E, Gendo A, Madl C, Gangl A.
ludwig.kramer@akh-wien.ac.at
Serum bilirubin levels are commonly used to assess extracorporeal
detoxification by liver support systems. We tested the hypothesis
that intravenous colloids administered before liver support treatment
could confound bilirubin values. Eight cirrhotic patients received
an infusion of a 6% hydroxy ethyl starch solution (10 ml/kg, 30
minutes) before detoxification using a liver support system (FPSA).
Bilirubin was measured before and 1 hour after infusion, and after
FPSA treatment (7 hours). Infusion of hydroxy ethyl starch was
associated with a drop in bilirubin values (mean, 18%, range,
1-44%, p=0.03 versus baseline values). Bilirubin levels were further
reduced during FPSA treatment (mean, 27%, range, 22-34%; p=0.02
versus pretreatment values). In conclusion, hydroxy ethyl starch
solution may decrease bilirubin levels in hyperbilirubinemic cirrhotic
patients receiving extracorporeal detoxification. The role of
potentially confounding factors in liver support studies is discussed
further.
Digestion. 2002;66(2):127-30.
Improved quality of life in patients with refractory
or recidivant ascites after insertion of transjugular intrahepatic
portosystemic shunts.
Gulberg V, Liss I, Bilzer M, Waggershauser T, Reiser M, Gerbes
AL.
Department of Medicine II, Klinikum of the University of Munich-Grosshadern,
Germany. Viet.Guelberg@med2.med.uni-muenchen.de
BACKGROUND: We have recently shown that the transjugular intrahepatic
portosystemic shunt (TIPS) is more effective than paracentesis
in the treatment of cirrhotic patients with severe ascites and
can prolong survival in selected patients. Although an improved
quality of life (QOL) has been suggested in these patients after
the TIPS procedure, so far there are no data available to substantiate
this assumption. Therefore, the aim of this study was to determine
the effect of TIPS on the QOL in cirrhotic patients with refractory
or recidivant ascites. METHODS: 21 cirrhotic patients who underwent
TIPS for refractory or recidivant ascites were investigated. All
patients were pretreated with repeated paracentesis for at least
1 year. Before the procedure and at 3 and 6 months during follow-up,
the patients themselves rated QOL, fatigue and physical performance
on a visual analogue scale (range 0-100). Furthermore, QOL was
determined by the QOL index (range 0-10) according to Spitzer.
RESULTS: Patients' rating of the QOL on the visual analogue scale
significantly increased from 35 +/- 25 (baseline) to 64 +/- 28
(3 months), and 66 +/- 24 (6 months; p = 0.02). Similarly, the
QOL index significantly increased from 6.9 +/- 2.0 (baseline)
to 8.3 +/- 2.1 (3 months), and 8.6 +/- 1.7 (6 months; p < 0.001).
The increase of QOL was more pronounced in patients with complete
response to TIPS. CONCLUSIONS: We demonstrate that TIPS for refractory
or recidivant ascites improves the QOL in patients with cirrhosis.
Our data indicates that this improvement is dependent on the response
to therapy. Copyright 2002 S. Karger AG, Basel
Aliment Pharmacol Ther. 2002 Dec;16 Suppl 5:12-23.
Review article: volume expansion in patients with
cirrhosis.
Henriksen JH, Kiszka-Kanowitz M, Bendtsen F.
Department of linical Physiology 239, Hvidovre Hospital, University
of Copenhagen, Denmark. jens.h.henriksen@hh.hosp.dk
Adequate size and distribution of the circulating medium are
important for cardiovascular function, tissue oxygenation, and
fluid homoeostasis. Patients with cirrhosis have cardiovascular
dysfunction with a hyperkinetic systemic circulation, abnormal
distribution of the blood volume, vasodilation with low systemic
vascular resistance, increased whole-body vascular compliance,
and increased arterial compliance. The effectiveness and temporal
relations of plasma/blood volume expansion depend highly on the
type of load (water, saline, oncotic material, red blood cells).
Patients with cirrhosis respond in some aspects differently from
healthy subjects, owing to their disturbed circulatory function
and neurohormonal activation. Thus the increase in cardiac output
and suppression of the renin-angiotensin-aldosterone system and
sympathetic nervous system during volume expansion may be somewhat
blunted, and in advanced cirrhosis, especially the non-central
parts of the circulation, including the splanchnic blood volume,
are expanded by a volume load. Infusion of oncotic material (preferably
albumin) is important in the prevention of post-paracentesis circulatory
dysfunction. In conclusion, volume expansion in advanced cirrhosis
is qualitatively and quantitatively different from that of healthy
subjects, and in those with early cirrhosis. Timely handling is
essential, but difficult as it is a balance between the risks
of excess extravascular volume loading and further circulatory
dysfunction in these patients with a hyperdynamic, but hyporeactive,
circulation.
Aliment Pharmacol Ther. 2002 Dec;16 Suppl 5:24-31.
Review article: albumin for circulatory support
in patients with cirrhosis.
Gines P, Guevara M, De Las Heras D, Arroyo V.
Liver Unit, Institut de Malalties Digestives, Hospital Clinic,
Barcelona, Spain. gines@medicina.ub.es
Renal function abnormalities and ascites in cirrhosis are the
final consequence of a circulatory dysfunction characterized by
marked splanchnic arterial vasodilation. This causes a reduction
in effective arterial blood volume and the homoeostatic activation
of vasoconstrictor and sodium-retaining systems. Albumin is very
effective in preventing renal failure associated with large-volume
paracentesis and spontaneous bacterial peritonitis, conditions
that are known to cause an impairment of circulatory function
in patients with cirrhosis and ascites. Moreover, albumin administration
improves survival in patients with spontaneous bacterial peritonitis.
In patients with hepatorenal syndrome the administration of vasoconstrictor
drugs in combination with albumin improves circulatory and renal
function markedly and survival slightly. By contrast, the administration
of albumin without vasoconstrictors has marginal or no effects
on renal function in this setting.
Aliment Pharmacol Ther. 2002 Dec;16 Suppl 5:1-5.
Review article: albumin in the treatment of liver
diseases—new features of a classical treatment.
Arroyo V.
Liver Unit, Institute of Digestive Diseases, Hospital Clinic,
University of Barcelona, Spain. arroyo@medicina.ub.es
Albumin was introduced initially in the treatment of patients
with cirrhosis and ascites to increase serum albumin concentration
due to its oncotic effect. Although its administration declined
some years later, at present it constitutes an essential treatment
in clinical hepatology. Several studies have clearly demonstrated
its efficacy in the prevention and treatment of circulatory dysfunction
and hepatorenal syndrome in patients with cirrhosis. These effects
can be due not only to its properties as a plasma expander but
also to its capacity to bind numerous substances such as bile
acids, nitric oxide and cytokines. Based on this capacity an albumin
dialysis system (MARS) has recently been developed. The usefulness
of this system in the management of patients with acute and chronic
liver failure is, at present, under evaluation.
Hepatology. 2002 Nov;36(5 Suppl 1):S185-94.
Treatment of patients with hepatitis C and cirrhosis.
Wright TL.
Gastroenterology Section, Veterans Affairs Medical Center, University
of California, San Francisco, USA. twright@itsa.ucsf.edu
Recommendations for treatment of hepatitis C in patients with
cirrhosis are difficult. Few prospective studies have focused
on treatment of patients with advanced disease, and response rates
appear to be lower and serious side effects more frequent in patients
with cirrhosis. In patients with compensated cirrhosis, combination
therapy with interferon alfa (3 million units [MU] 3 times a week)
and ribavirin (1,000 or 1,200 mg/d) results in a sustained virological
response (SVR) in 33% to 41% of patients. Responses to combination
therapy are not significantly higher using peginterferon alfa
2a (180 microg/wk; 43%) or peginterferon alfa 2b (1.5 microg /kg/wk;
44%) compared with standard interferon. In using peginterferon
in combination therapy, the benefits of once weekly dosing need
to be weighed against the higher risks of cytopenias and greater
costs with the pegylated formulations. Combination therapy results
in some degree of histological improvement even in patients who
are virological non-responders. These findings provide the scientific
basis for ongoing studies of maintenance therapy with peginterferon
to prevent complications of cirrhosis in non-responder patients
with hepatitis C. Recommendations for management of decompensated
cirrhosis and of recurrent hepatitis C after liver transplantation
are difficult because of limitations of data, most of which are
derived from uncontrolled case series. Combination therapy is
poorly tolerated in both groups and rates of response are low.
Thus, while the medical need is great, treatment of patients with
decompensated cirrhosis or with recurrent hepatitis C after transplantation
should be undertaken cautiously and only within the confines of
prospective clinical trials.
Hepatology. 2002 Nov;36(5):1197-205.
Pharmacodynamic effects of a nonpeptide antidiuretic
hormone V2 antagonist in cirrhotic
patients with ascites.
Guyader D, Patat A, Ellis-Grosse EJ, Orczyk GP.
Clinique des maladies du foie and Inserm U522, Rennes, France.
Dominique.Guyader@univ-rennes1.fr
Water retention and dilutional hyponatremia, mainly attributable
to an impairment of free water excretion and increased vasopressin
activity, are well-documented complications in cirrhotic patients
with ascites. VPA-985 is a selective, nonpeptide, orally active,
vasopressin-2-receptor antagonist. The aim of this study was to
determine the pharmacodynamics, safety, and pharmacokinetics of
ascending single doses (25, 50, 100, 200, and 300 mg) in cirrhotic
patients with ascites in a randomized, double-blind, placebo-controlled
trial. Each dose level was studied in 5 patients (4 active and
1 placebo). After an overnight fast and fluid restriction (continued
for 4 hours after dose administration), all patients were given
placebo on baseline day and an oral suspension of VPA or placebo
on the following day. VPA produced a significant dose-related
increase in daily urine output (1,454 +/- 858 mL to 4,568 +/-
4,385 mL with VPA 300 mg) and a dose-related decrease in urine
osmolality. The free water clearance reached greater than 3 mL/min
for doses 100 mg or greater. Simultaneously, significant increases
in serum osmolality, sodium, and vasopressin levels were found.
There was a significant increase in sodium urine excretion. VPA
was rapidly absorbed and maximum serum concentrations were achieved
within 1 hour after administration. Elimination half-life ranged
from 9.0 hours after 100 mg to 22.6 hours after 200 mg. In conclusion,
VPA induced a dose-related aquaretic response, suggesting a therapeutic
potential in managing water retention in patients with liver cirrhosis
with ascites.
J Clin Gastroenterol. 2002 Nov-Dec;35(5):403-5.
The effect of mannitol infusion on the response
to diuretic therapy in cirrhotic patients with ascites.
Pamuk ON, Sonsuz A.
Department of Internal Medicine, Cerrahpasa Medical Faculty, University
iof Istanbul, Turkey. onpamuk80@hotmail.com
GOALS: A good response to diuretics is obtained initially in
the treatment of cirrhotic ascites. However, unresponsiveness
to therapy and various complications may develop with disease
progression. This makes obligatory the search for new treatment
methods that may be alternative to standard diuretics. In our
study, we investigated the effect of mannitol infusion on current
therapies in patients with cirrhotic ascites who were using diuretic
treatment. BACKGROUND: Thirty cirrhotic patients with ascites
who were using diuretic treatment were included in the study.
The patients were randomly divided into two groups; a dose of
100-mL 20% mannitol was administered to the first group, and 100-mL
5% dextrose solution was administered to the second group. The
patients' urinary volumes and serum and urine electrolyte levels
(sodium, potassium) were determined before and after the test.
RESULTS: In the mannitol group, a significant increase in urinary
volume was observed (p < 0.05). However, in the control group
no significant differences in urinary sodium excretion were observed
after the test (p > 0.05). In the mannitol group, a concomitant
increase in urinary volume and sodium excretion was observed in
eight cases (53%). The urinary sodium excretions and serum sodium
levels before the test were significantly lower in patients who
responded to mannitol than in patients who did not respond (p
= 0.001 and p = 0.04, respectively). CONCLUSIONS: As a result,
short-term mannitol therapy makes a significant contribution to
diuretic therapy in approximately half of cases with cirrhotic
ascites. The results we obtained suggest that mannitol may be
a useful alternative in the treatment of ascites.
Indian J Gastroenterol. 2002 Jul-Aug;21(4):145-8
Hemodynamic effect of spironolactone in liver
cirrhosis and propranolol-resistant portal hypertension.
Sen S, De Binay K, Biswas PK, Biswas J, Das D, Maity AK.
Department of Medicine, Institute of Post Graduate Medical Education
and Research, Calcutta.
OBJECTIVE: In a proportion of patients with liver cirrhosis,
portal pressure does not decrease adequately with propranolol.
These patients may benefit from another drug that may reduce portal
pressure. We evaluated the role of spironolactone, alone or with
propranolol, in such patients. METHODS: Patients with cirrhosis,
with or without ascites, with esophageal varices and with hepatic
venous pressure gradient exceeding 12 mmHg, which did not show
a 20% reduction after an 80-mg oral dose of propranolol, were
studied. They were allocated to receive spironolactone 100 mg
orally once daily either alone (group 1, n=10) or with propranolol
40 mg orally twice daily (group 2, n=10), for 7 days, after which
the hemodynamic study was repeated. RESULTS: Hepatic venous pressure
gradient decreased in those receiving spironolactone and propranolol
(p=0.007); 5 patients in group 1 and 7 in group 2 showed a reduction
in hepatic venous pressure gradient by more than 20%. However,
the reduction produced by spironolactone alone (20.5 [31.3]%)
was not significantly different from that produced by combination
therapy (30.3 [25.9]%; p=0.46). CONCLUSION: Spironolactone in
combination with propranolol achieves adequate reduction (>
or = 20%) in hepatic venous pressure gradient in propranolol-resistant
portal hypertension in patients with liver cirrhosis. Spironolactone
alone was also effective in some patients.
Int J Mol Med. 2002 Nov;10(5):647-8.
Additional benefit of lamivudine treatment as
a preventive therapy for hepatic encephalopathy in patients with
decompensated liver cirrhosis associated with hepatitis B.
Hanada S, Kumashiro R, Kaji R, Harada M, Sata M.
Second Department of Medicine, Kurume University School of Medicine,
Kurume, Japan. hanadas@med.kurume-u.ac.jp
Lamivudine has previously been found to be effective not only
in patients with compensated liver disease due to hepatitis B
virus (HBV) but also in those with hepatic decompensation. However,
long-term follow-up of patients with hepatic encephalopathy (HE)
has not been previously reported. We describe a patient with recurrent
HE associated with decompensated liver cirrhosis due to hepatitis
B. After the initiation of treatment with lamivudine, manifestation
of HE has not been observed for about 2 years and liver function
has improved as well. This experience suggests that improved liver
function using lamivudine may contribute to prevention from recurrence
of HE.
Hepatology. 2002 Oct;36(4 Pt 1):949-58.
Albumin dialysis in cirrhosis with superimposed
acute liver injury: a prospective, controlled study.
Heemann U, Treichel U, Loock J, Philipp T, Gerken G, Malago M,
Klammt S, Loehr M, Liebe S, Mitzner S, Schmidt R, Stange J.
Department of Internal Medicine, University of Essen, Germany.
Patients with liver cirrhosis and a superimposed acute injury
with progressive hyperbilirubinemia have a high mortality. A prospective,
controlled study was performed to test whether hyperbilirubinemia,
30-day survival, and encephalopathy would be improved by extracorporeal
albumin dialysis (ECAD). Twenty-four patients were studied; 23
patients had cirrhosis; 1 had a prolonged cholestatic drug reaction
and was excluded from per protocol (PP) analysis. Patients had
a plasma bilirubin greater than 20 mg/dL and had not responded
to prior standard medical therapy (SMT). Patients were randomized
to receive SMT with ECAD or without (control). ECAD was performed
with an extracorporeal device that dialyzes blood in a hollow
fiber dialyzer (MW cutoff < 60 kd) against 15% albumin. Albumin-bound
molecules transfer to dialysate albumin that is regenerated continuously
by passage through a charcoal and anion exchange column and a
conventional dialyzer. ECAD was associated with improved 30-day
survival (PP, 11 of 12 ECAD, 6 of 11 controls; log rank P <.05).
Plasma bile acids and bilirubin decreased on average by 43% and
29%, respectively, in the ECAD group after 1 week of treatment,
but not in the control group. Renal dysfunction and hepatic encephalopathy
improved in the ECAD group, but worsened significantly in the
control group. ECAD was safe, with adverse events being rare and
identical in both groups. In conclusion, ECAD appears to be effective
and safe for the short-term treatment of patients with cirrhosis
and superimposed acute injury associated with progressive hyperbilirubinemia
and may be useful for increasing survival in such patients awaiting
liver transplantation.
Hepatogastroenterology. 2002 Sep-Oct;49(47):1445-8.
Long-term hematological and biochemical effects
of partial splenic embolization in hepatic cirrhosis.
Tajiri T, Onda M, Yoshida H, Mamada Y, Taniai N, Kumazaki T.
First Department of Surgery, Nippon Medical School, 1-1-5 Sendagi,
Bunkyo-ku, Tokyo 113-8603, Japan. tajirit@nms.ac.jp
BACKGROUND/AIMS: Partial splenic embolization was developed
as a non-surgical treatment for hypersplenism, but recently splenic
embolization has been reported to improve the hepatic function.
We undertook long-term evaluation of partial splenic embolization
in patients with hepatic cirrhosis in comparison with patients
not undergoing embolization. METHODOLOGY: We performed embolization
in 26 patients with cirrhosis. The controls consisted of 26 with
cirrhosis patients who were not undergone embolization. RESULTS:
Red blood cell counts of embolized patients had increased significantly
at 6 months after the procedure, remaining increased for up to
7.5 years. Platelet counts increased maximally by 2 weeks after
embolization, followed by a gradual decrease. Nonetheless, platelets
remained significantly more numerous than before embolization
for up to 8 years. Neither aspartate aminotransferase nor alanine
aminotransferase activities in serum changed significantly during
follow-up. Choline esterase activity increased significantly by
6 months after embolization and remained increased for more than
7 years. Serum albumin concentration increased significantly,
beginning at 6 months after embolization; this increase was maintained
for 6 years. Survival did not differ between embolized and non-embolized
groups. CONCLUSIONS: Partial splenic embolization is a beneficial
non-surgical treatment that enhances hepatic protein synthetic
capacity as well as alleviating hypersplenism in patients with
cirrhosis.
Dig Liver Dis. 2002 Jul;34(7):523-7.
Improved liver tests and greater biliary enrichment
with high dose ursodeoxycholic acid in early stage primary biliary
cirrhosis.
Roda E, Azzaroli F, Nigro G, Piazza F, Jaboli F, Ferrara F, Liva
S, Giovanelli S, Miracolo A, Colecchia A, Festi D, Mazzeo C, Bacchi
L, Roda A, Mazzella G.
Department of Internal Medicine and Gastroenterology, University
of Bologna, S. Drsola-Malpighi Hospital, Italy.
BACKGROUND: Ursodeoxycholic acid is currently used for the
treatment of primary biliary cirrhosis at 13-15 mg/kg/day, but
liver tests of some patients do not return to normal at this dose.
Studies reported here were designed to test whether a higher dose
of ursodeoxycholic acid than is currently used would induce still
greater biliary enrichment of ursodeoxycholic acid and whether
such enrichment would lead to still further improvement in liver
tests in patients with early primary biliary cirrhosis. METHODS:
A total of 20 patients with histologically proven primary biliary
cirrhosis were enrolled. Patients had early stage primary biliary
cirrhosis as serum bilirubin levels were normal and the Mayo risk
score 4.2 +/- 0.5. Group 1 received 600, 1200 and 1800 mg/day
of ursodeoxycholic acid; group 2 received 900, 1500 and 2100 mg/day.
The order of periods was randomized. Each treatment period lasted
3 months followed by a further 3 months during which a standard
dose of ursodeoxycholic acid was given. At the end of each treatment
period, liver tests were evaluated, and biliary bile acid pattern
of duodenal bile was determined using high pressure liquid chromatography.
RESULTS: Biliary bile acid became enriched in ursodeoxycholic
acid in direct relationship to dosage [r = 0.84, p < 0.001).
At doses of 1800 mg/day (25-35 mg/kg/day), biliary ursodeoxycholic
acid averaged 69 +/- 6.6%. A progressive decrease of alanine aminotransferase
[p < 0.0001), aspartate aminotransferase [p < 0.001) and
alkaline phosphatase [p < 0.02) was observed with increasing
concentrations of ursodeoxycholic acid in bile. Biochemical liver
tests showed a stronger correlation with biliary concentrations
of ursodeoxycholic acid than with the administered dose. CONCLUSIONS:
In early primary biliary cirrhosis, higher dose ursodeoxycholic
acid appears to be more effective than doses currently recommended.
J Gastroenterol Hepatol. 2002 Aug;17(8):882-8.
Clinical course, predictive factors and prognosis
in patients with cirrhosis and type 1 hepatorenal syndrome treated
with Terlipressin: a retrospective analysis.
Colle I, Durand F, Pessione F, Rassiat E, Bernuau J, Barriere
E, Lebrec D, Valla DC, Moreau R.
Laboratoire d'Hemodynamique Splanchmique et de Biologie Vasculaire,
Institut National de la Sante et de la Recherge Medicale, Clinchy,
France. Isabelle.Colle@rug.ac.be
BACKGROUND AND AIM: Terlipressin has been proposed to treat
renal failure in patients with type 1 hepatorenal syndrome (HRS).
However, the predictive factors for improved renal function and
survival are unknown in patients with type 1 HRS treated with
terlipressin. The aim of the present retrospective study was to
investigate the predictive factors and prognosis of patients with
type 1 HRS treated with terlipressin. METHODS: The clinical charts
of 18 consecutive patients with cirrhosis and type 1 HRS treated
with terlipressin were studied. The predictive factors for improved
renal function and survival were identified using univariate analyses.
RESULTS: Improved renal function, indicated by a significant decrease
in serum creatinine (61 +/- 4%), occurred in 11 (60%) patients.
The only predictive factor for improved renal function was a Child-Pugh's
score < or =13 at the time of diagnosis of HRS (P = 0.02).
Fifteen patients (83%) died at 45 days and the median survival
was 24 days. Of the three patients who survived, two underwent
successful orthotopic liver transplantation. Three predictive
factors for survival were identified: absence of a precipitating
factor for HRS (P = 0.012); improved renal function during terlipressin
therapy (P = 0.05); and a dose of terlipressin > or =3 mg/day
(P = 0.04). CONCLUSIONS: In patients with type 1 HRS treated with
terlipressin, patients with improved renal function had less severe
cirrhosis (Child-Pugh >10 but < or =13) than patients without.
The predictive factors for survival were the absence of a precipitating
factor for HRS, the terlipressin-induced improvement in renal
function and a dose of terlipressin of at least 3 mg/day. These
findings suggest that a randomized controlled trial investigating
the effect of terlipressin on survival in patients with type 1
HRS should be performed. Copyright 2002 Blackwell Publishing Asia
Pty Ltd
Hepatogastroenterology. 2002 Jul-Aug;49(46):1102-8.
Antifibrotic properties of botanicals in chronic
liver disease.
Stickel F, Brinkhaus B, Krahmer N, Seitz HK, Hahn EG, Schuppan
D.
Department of Medicine I, Division of Hepatology, Division of
Complementary Medicine, University of Erlangen-Nuremberg, Ulmenweg
18, D-91054 Erlangen, Germany. felix.stickel@med1.imed.uni-erlangen.de
Cirrhosis of the liver is a major complication of various chronic
liver diseases and results from excess production and decreased
degradation of extracellular matrix. Proinflammatory cytokines,
toxic metabolites and certain drugs can trigger enhanced fibrogenesis
in hepatic stellate cells and myofibroblasts, the major matrix-producing
cells. Since treatment of established cirrhosis is limited, therapeutic
interventions that inhibit or mitigate fibrogenesis are needed.
Numerous drugs have been investigated for their antifibrotic potential
and botanicals constitute a significant fraction of them. Colchicine
has been used to treat various chronic liver diseases with controversial
results. To date, there is a lack of studies in appropriate animal
models and well-controlled human trials to demonstrate its antifibrotic
properties. Silymarin has so far failed to clearly show an antifibrotic
effect in human studies, whereas animal experiments suggest that
this mixture of flavolignanes may be beneficial in patients which
have not yet developed cirrhosis. Animal studies indicate an antifibrotic
potential of Shosaiko-to, a herbal combination frequently used
in China and Japan for the treatment of chronic viral hepatitis,
but mechanisms of action need to be further explored. Other botanicals
include trans-resveratrol, a flavonoid extracted from grapevine,
and Salvia miltiorrhiza which were shown to interfere with the
process of hepatic stellate cell activation. Herbal combinations,
such as compound 861 and LIV.52 were advocated as antifibrotics
or hepatoprotectives, but studies in humans have either been of
questionable design or resulted in cessation of the trial due
to adverse outcomes.
Liver. 2002 Jun;22(3):235-44.
An electron microscopic and morphometric study
of ursodeoxycholic effect in primary biliary cirrhosis.
Neuman MG, Cameron RG, Haber JA, Katz GG, Blendis LM.
Division of Clinical Pharmacology, Sunnybrook and Women's Health
Sciences Centre, Toronto, Ontario, Canada. manuela@sten.sunnybrook.utoronto.ca
BACKGROUND/AIMS: Primary biliary cirrhosis (PBC) is a chronic
liver disease that results in cholestasis and bile duct loss.
Ursodeoxycholic acid (UDCA) has been shown to reduce hepatocellular
damage in PBC. The study attempted to quantify perisinusoidal
collagenization and the number of apoptotic bodies in PBC liver
biopsies from patients in a randomized control trial treated with
UDCA compared to those who received placebo. METHODS: Twenty-eight
patients with PBC (10 cirrhotic, 18 non-cirrhotic; 13 treated
with UDCA, 15 treated with placebo) were compared with 32 controls
with normal hepatic histology on light microscopy. Liver biopsies
were examined for degree of perisinusoidal fibrosis and apoptotic
activity using electron microscopy. RESULTS: The degree of perisinusoidal
fibrosis and apoptotic activity was similar in pretreatment biopsies
of UDCA and placebo-treated patients. After two years of placebo,
patients showed a significant increase in fibrosis (P < 0.001).
In contrast, there were no changes in non-cirrhotic and a decrease
in fibrosis in cirrhotic patients given UDCA. At baseline, PBC
patients had higher numbers (apoptotic cells/100 hepatocytes +/-
SE) of apoptotic cells (7 +/- 3), than controls (2 +/- 0.5) (P
< 0.05), with no difference between cirrhotic and non-cirrhotic
patients in the two groups of patients. After two years, the numbers
of apoptotic cells in UDCA-treated patients decreased significantly
compared to baseline (3 +/- 2) (P < 0.05); with placebo patients
the number of apoptotic cells increased (12 +/- 5) (P < 0.05).
CONCLUSION: Treatment with UDCA prevents the deposition of perisinusoidal
collagen and reduces the apoptotic activity in PBC patients after
2 years of therapy.
Rev Med Chir Soc Med Nat Iasi. 2001 Jan-Mar;105(1):63-8.
[Portal hypertension in liver cirrhosis]
[Article in Romanian]
Prelipcean CC.
Clinica a II-a Medicala Gastroenterologie, Facultatea de Medicina,
Universitatea de Medicina si Farmacie Gr.T. Popa Iasi.
Portal hypertension is a dramatic complication in liver cirrhosis
by efraction of the varices localized more frequently in the esophagus.
It has been an actual subject due to physiopathological research
(endotelin system, nitric system etc), diagnosis (echoendoscopy,
color Doppler), and therapeutically progress. Propranolol, available
at a low cost, is efficient and unanimously accepted in the prophylactic
treatment of medium and large varices which have never bled as
well as in the hemorrhage due to variceal efraction which stopped
therapeutically or spontaneously. This drug diminishes the risk
of rebleeding. Besides the pharmacological treatment, terlipresine,
octreotid, sclerotherapy and bandlegation are used in active hemorrhage
due to variceal efraction. If this fails other methods for haemostasis
are used: portosystemic transjugular shunt, mechanical tamponade,
selective surgery and ideally hepatic transplant. Except for the
hepatic transplant, none of the mentioned methods can improve
the rate of survival in-patients, which depends on the state of
the hepatic failure.
J Hepatol. 2002 Jul;37(1):15-21.
Effects of long-term oral misoprostol administration
on hepatic amino acid-nitrogen metabolism in patients with cirrhosis.
Bianchi G, Brizi M, Manini R, Fabbri A, Loffreda S, Zoli M, Marchesini
G.
Dipartimento di Medicina Interna, Cardioangiologia, Epatologia,
Alma Mater Studiorum, Universita di Bologna, Policlinico S. Orsola-Malpighi,
Bologna, Italy. bianmice@almadns.unibo.it
BACKGROUND: The acute infusion of a Prostaglandin of E series
1 (PGE1) analogue results in nitrogen sparing in cirrhosis. AIMS:
To test the effects of long-term oral PGE1 on hepatic and whole-body
nitrogen metabolism. PATIENTS AND METHODS: Ten patients with advanced
cirrhosis were studied in paired experiments, before and 30-50
days after oral misoprostol therapy. alpha-Amino-nitrogen levels
and urea-nitrogen synthesis rate were measured in the post-absorptive
state and in response to continuous alanine infusion (2 mmol/kg
per hour for 4.5h). Data were used to compute the functional hepatic
nitrogen clearance, i.e. the slope of the regression of alpha-amino-N
levels to urea-N synthesis rate, and the apparent nitrogen exchange.
RESULTS: Misoprostol reduced urea-N synthesis rate (during fasting
and in response to alanine), resulting in a positive nitrogen
exchange. The functional hepatic nitrogen clearance slightly increased,
and the regression line was rightwards shifted, indicating a reduced
urea synthesis rate at any alpha-amino-N concentration. Amino
acid- and ammonia-N did not accumulate in plasma. No systematic
effects on insulin and glucagon were observed. CONCLUSIONS: Data
are consistent with a nitrogen sparing mechanism of misoprostol,
not mediated by hormone levels. These effects may be beneficial
in clinical hepatology, and need to be tested in controlled trials.
Lik Sprava. 2002;(2):64-8.
[Different therapeutic approaches for chronic
diffuse liver lesions using ornicetil, lactulose, etimizol and
corinfar]
[Article in Ukrainian]
Neiko IeM, Mytnyk ZM, Holovach IIu.
Different therapeutic regimens were tried in 67 patients with
hepatic cirrhosis and in 54 patients with chronic hepatitis depending
on the leading pathological syndrome. Treatment schemes involved
the use of the drug ornicetil in patients having acute episodes
of portal systemic encephalopacy, lactulose in those presenting
with an increased content of ammonia in the blood and symptoms
of chronic portal systemic encephalopacy; etimizol was given to
those patients with an apperant antioxidant imbalance. Differentiated
approaches to the institution of curative measures permitted improving
considerably the patients' medical rehabilitation, achieving regression
of pathological manifestations. It has been found out that the
above drugs exert a positive effect on the cytolytic and mesenchimal-inflammatory
syndromes and will, we believe, come to be widely used for treating
diffuse lesions of the liver.
Hepatogastroenterology. 2002 May-Jun;49(45):783-7.
Effects of losartan, somatostatin and losartan
plus somatostatin on portal hemodynamics and renal functions in
cirrhosis.
Hulagu S, Senturk O, Erdem A, Ozgur O, Celebi A, Karakaya AT,
Seyhogullari M, Demirci A.
Department of Gastroenterology, Kocaeli University, Faculty of
Medicine, Kocaeli, Turkey. shulagu@hotmail.com
BACKGROUND/AIMS: Several drugs have been used to reduce portal
hypertension. Losartan constitutes arteriolar and venous vasodilation
by inhibiting the effects of the increased angiotensin II in cirrhotic
patients. In this study, we analyzed the effects of losartan,
when used alone and when combined with somatostatin, on portal
and renal hemodynamics. METHODOLOGY: Seventeen patients with cirrhosis
were enrolled. During the study, the patients were administered
250 micrograms of somatostatin i.v. bolus and subsequent infusion
at a rate of 250 micrograms/hr for 2 hours on the second day;
25 mg losartan orally on the fourth day; and losartan and somatostatin
together, in the same doses as the second and the fourth day,
were given on the sixth day. RESULTS: The portal flow volume and
the velocity that were measured after the administration of somatostatin,
losartan and the combination of each drug, were found to be increased
when compared with the initial values (P < 0.001). Additionally,
the creatinine clearances were increased and statistically significant
with somatostatin. CONCLUSIONS: Considering its low cost, easy
usability, long lasting effect, we suggest that losartan can be
used as an alternative treatment in the clinical conditions where
portal pressure should be reduced and can be combined with somatostatin
without any significant adverse effects.
Nippon Geka Gakkai Zasshi. 2002 May;103(5):408-13.
[Liver transplantation for patients with hepatitis
B/C virus cirrhosis or hepato cellular carcinoma]
[Article in Japanese]
Todo S, Furukawa H, Matsushita M, Shimamura T, Jin MB, Suzuki
T, Taniguchi M.
Hokkaido University School of Medicine, Department of General
Surgery.
The outcome of liver transplantation for patients with hepatitis
B/C virus (HBV/HBC) cirrhosis or with hepatocellular carcinoma(HCC)
was deemed pessimistic until the early 1990s due to the high rate
of recurrence and mortality. However, with the advent of new antiviral
agents and strict adherence transplant indications, the results
of liver transplantation in patients with these disease have improved
progressively. Coadministration of lamivudine and anti-HBV immunoglobulin,
and of interferon and ribavirin inhibits the recurrence of hepatitis
B and hepatitis C, respectively. Excluding HCC patients with extrahepatic
or lymph node metastasis, vascular invasion, a single lesion more
than 5 cm in diameter, or multiple lesions more than 3 cm in diameter,
the 5-year patient survival rate has improved from 30% to 85%,
with a disease-free survival rate of more than 90%. However, the
development of lamivudineresistant mutants after prolonged use
of the agent needs to be overcome, possibly by new antiviral agents
such as adefovir. In addition, to expand the current limited transplant
indications for HCC, the efficacy of perioperative anticancer
treatment and the importance of molecular diagnosis of circulating
hepatoma cells must be determined in future.
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