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HEPATOLOGY WATCH® |
Editorial Board:
Emmet B. Keeffe, MD (Chair); M. Eric Gershwin, MD; Ira S. Goldman, MD; John
L. Gollan, MD, PhD; Kris V. Kowdley, MD; Paul Martin, MD; Marion G. Peters,
MD |
NOVEMBER 2004
CHRONIC HEPATITIS B VIRUS (HBV)
INFECTION
Lamivudine for patients with
advanced liver disease. Yun-Fan
Liaw and colleagues randomized patients with chronic hepatitis B and advanced
hepatic fibrosis or cirrhosis to receive lamivudine 100 mg/d (n=436) or placebo
(n=215). Time to disease progression
(i.e., hepatic decompensation, hepatocellular carcinoma [HCC], spontaneous
bacterial peritonitis, bleeding varices, or death related to liver disease) was
the primary end point of the study.
After a median duration of treatment of 32.4 mo (range, 0-42 mo), a
significantly greater percentage of patients in the placebo vs. lamivudine
group had developed disease progression (17.7% vs. 7.8%; p=0.001) and the study
was terminated. The Child-Pugh score increased
in only 3.4% of lamivudine-treated patients compared to 8.8% of placebo-treated
patients (p=0.02). Furthermore, HCC
occurred in a lower percentage of patients in the lamivudine vs. placebo
treatment group (3.9% vs. 7.4%; p=0.047).
YMDD mutations developed in 49% of lamivudine-treated patients, and the
Child-Pugh score was more likely to increase in these patients than in other
patients treated with lamivudine (7% vs. <1%). These findings demonstrated that lamivudine
treatment reduced the incidence of hepatic decompensation and the risk of HCC
in patients with chronic hepatitis B and advanced fibrosis or cirrhosis. (Liaw Y-F, et
al. N Engl J Med 2004;351:1521-1531)
HBV
genotypes. Scott Fung
and Anna Lok briefly summarize the growing body of evidence that HBV genotype
correlates with clinical outcomes in patients with HBV infection in an
editorial in the October 2004 issue of Hepatology. The most important information on the
relationship of HBV genotype and outcomes has been provided by observations of
differences between patients infected with genotypes B and C. There is also evidence that there are
differences in response to interferon, but not to nucleoside or nucleotide
analogues, between genotypes. In
addition, there is a clear association between HBV genotype and precore and
core promoter mutations. The authors
also comment on an article in the October 2004 issue of Hepatology by Garfein
et al. (Hepatology 2004;40:865-873) that reports several cases of fulminant
hepatitis among a population of American Indians due to HBV genotype D
infection. Full-length HBV genomic
sequence data confirmed a common source for the outbreak and also demonstrated
that the HBV strain did not invariably lead to a fulminant course. The authors conclude that genotyping remains
a research tool that may in the future be used to predict risk for adverse
outcomes or guide treatment. (
Genotype C and risk for HCC. H. L-Y Chan and coworkers at the
Prince of Wales Hospital in
PORTAL HYPERTENSION
Predictors of early mortality. Douglas Heuman et al. report data
from 296 cirrhotic patients referred for liver transplantation prior to
February, 2002. Sixty-one (21%) died
within 180 days of referral without transplantation, and the median initial
Model for End-stage Liver Disease (MELD) score was 21 for the patients who
died. For patients with an initial MELD
score <21, low serum sodium (<135 meq/L) and persistent ascites were
independent predictors of early mortality.
For patients with an initial MELD score >21, only the MELD score was
predictive for early mortality. The
authors concluded that ascites and hyponatremia merit further study as
prognostic indicators and listing criteria in patients needing liver
transplantation. (Heuman DM, et al. Hepatology 2004;40:802-810)
Prophylaxis of growth of small
esophageal varices. Carlo
Merkel et al. conducted a placebo-controlled, multicenter study in which 161
patients with cirrhosis and small esophageal varices (F1) without previous
bleeding were randomized to receive either nadolol or placebo. The daily dose of nadolol was adjusted to
decrease the resting heart rate by 25% (mean dose = 62 ± 25 mg/d). The primary end point was the occurrence of large
esophageal varices (F2 or F3).
Endoscopic examination was performed every 12 mo for 60 mo of
follow-up. Nine nadolol-treated vs. 29
placebo-treated patients developed growth of varices; the cumulative risk for
growth was 20% vs. 51%, respectively. The cumulative probability for variceal
bleeding was lower in the nadolol group, but no difference in survival was
observed between groups. This study
suggests that beta-blocker prophylaxis of variceal bleeding in compensated
cirrhosis should be started when small varices are identified. (Merkel C, et al. Gastroenterology 2004;127:476-484).
PRIMARY SCLEROSING CHOLANGITIS (PSC)
Effect of high-dose ursodeoxycholic
acid (UDCA). There is
evidence that high doses (≥ 20 mg/kg/d) of UDCA may be more effective
therapy for PSC than lower doses. This
increased effectiveness may be due to enrichment of biliary bile acids with
UDCA. However, the correlation between
UDCA dose and biliary enrichment had not been previously demonstrated. Daniel Rost and associates at the
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