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HEPATOLOGY WATCH® |
Editorial Board: Emmet
B. Keeffe, MD (Chair); |
OCTOBER 2004
CHRONIC HEPATITIS B VIRUS (HBV)
INFECTION
Peginterferon therapy for
HBeAg-negative chronic hepatitis B. Patients with HBeAg-negative chronic
hepatitis B have mutations in the precore or core promoter region, which
abolish or suppress expression of HBeAg, and typically have progressive liver
damage. These patients respond well to
lamivudine or adefovir therapy; however, relapse rates are high with cessation
of treatment, which has led to use of indefinite therapy. In patients with
HBeAg-negative chronic hepatitis B, Patrick Marcellin et al compared the safety
and efficacy of peginterferon alfa-2a (PEG IFN) 180 mg
weekly plus placebo (n=177), PEG IFN plus lamivudine 100 mg/d (n=179), and
lamivudine alone (n=181) in a multicenter, randomized, partially double-blind
study conducted in 54 sites in 13 countries, principally in Asia and
Europe. Patients were treated for 48
weeks followed by 24 weeks of follow-up.
Normalization of alanine aminotransferase levels and HBV DNA levels
below 20,000 copies/mL were significantly higher with PEG IFN monotherapy (59%
and 43%, respectively) and PEG IFN plus lamivudine (60% and 44%, respectively)
than with lamivudine monotherapy (44% and 29%, respectively) after
follow-up. Sustained suppression of HBV
DNA to below 400 copies/mL was 19%, 20% and 7%, respectively, in the three
groups. Loss of HBsAg occurred in 12
patients in the two PEG IFN groups, and no patient in the lamivudine
monotherapy group. Side effects were
typical of PEG IFN therapy, but rates of withdrawal were low (8% and 6%,
respectively) and rates in depression infrequent (3% and 4%, respectively) in
the PEG IFN groups. This study shows
higher sustained rates of response with PEG IFN therapy than with lamivudine,
and demonstrated that the addition of lamivudine to PEG IFN did not improve
response rates. (Marcellin P, et
al. N Engl J Med
2004;351:1206-1217)
CHRONIC HEPATITIS C VIRUS (HCV)
INFECTION
Treatment of patients with normal
ALT levels. Ira
Jacobson et al. conducted a study in which 56 chronic HCV patients with normal
ALT levels (at least 2 normal ALT levels ≥3 months apart) and detectable
HCV RNA were randomized to receive ribavirin (1,000-1,200 mg/day) plus either 3
or 5 million units of IFN alfa-2b thrice weekly. The sustained virological response (SVR) rate
was 32%. Patients with genotype 2 or 3
infection had a higher SVR rate than those with genotype 1 infection (80% vs.
24%). Genotype 1 patients treated with the higher dose of IFN had a trend
toward a higher SVR rate compared to those treated with lower dose IFN (36% vs.
10%; p = 0.07). No sustained ALT
elevations were noted. These data showed
that the SVR rate in patients with normal ALT levels was comparable to that
reported in patients with elevated ALT levels.
In an accompanying editorial, Bruce Bacon concluded that arguments to
limit therapy only to patients with elevated ALT levels are no longer
valid. (Jacobson IM, et al. Am J
Gastroenetrol 2004;99:1700-1705; Bacon BR. Am J Gastroenterol 2004;99:1708-1709)
PRIMARY BILIARY CIRRHOSIS (PBC)
Etiology, epidemiology and
treatment. PBC is an
autoimmune disease characterized by chronic inflammation and progressive
destruction of intrahepatic bile ducts.
While previous findings indicate that family members of patients with
PBC have a 100-fold higher risk of developing PBC than the general population,
no definitive genetic association has been found. In order to explore the contributions of
genetic and environmental factors associated with the development of PBC, Carlo
Selmi and colleagues evaluated the concordance rate of PBC among 8 sets of
monozygotic twins (genetically identical and share environmental background)
and 8 sets of dizygotic twins (genetically diverse and share environmental
background) identified within a 1,400-family cohort followed in several centers
throughout the world. Both twins in 5 of
8 monozygotic twin sets had PBC (pairwise concordance rate of 0.63), while no
dizygotic twin set was found to be concordant for PBC. The age of onset of PBC was similar in 4 of
the 5 concordant sets of monozygotic pairs.
These data show that genetic factors play a major role in the
development of PBC. However, the finding
of discordant monozygotic pairs for PBC suggests that epigenetic factors and/or
environmental factors are also important.
In a second study, S. Sood and others documented that the current
prevalence rate of PBC in Victoria, Australia is higher than it was in 1991 due
to an increased prevalence of PBC in the 3 largest migrant groups (British,
Italian, and Greek) compared to that of the Victoria population as a
whole. These results provide further
evidence of the importance of the role of environmental factors in the etiology
of PBC. Finally, in another study
conducted by Carlo Selmi and coworkers, previous data suggesting a retroviral
etiology for PBC was not confirmed. (Selmi C, et al. Gastroenterology
2004;127:485-492; Sood S, et al. Gastroenterology
2004;127:470-475; Selmi C, et al. Gastroenterology
2004;127:493-501)
CIRRHOSIS
Improved survival after variceal
bleeding. Nicolas
Carbonell and coworkers conducted a single-center retrospective review of the
clinical records of all cirrhotic patients admitted to the Liver Intensive Care
Unit (Universite Pierre and Marie Curie,
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