|
|
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 |
SEPTEMBER 2004
HEPATITIS C VIRUS (HCV) INFECTION
Treatment of patients coinfected
with human immunodeficiency virus (HIV). Chronic liver disease due
to HCV infection has become the leading cause of morbidity and mortality in
HIV/HCV coinfected patients. The treatment of chronic HCV infection in patients
coinfected with HIV/HCV was associated with low response rates in early
studies, and there has been concern that the adverse side effects of agents
used to treat HCV might be exacerbated in patients with HIV infection. More
recently, 3 randomized trials of the treatment of chronic HCV in HIV-infected
patients with peginterferon (PEG-IFN) plus ribavirin (RBV) have been conducted,
and two of these studies were recently published. In the first study, Francesca
Torriani et al. of the APRICOT (AIDS Pegasys Ribavirin International
Coinfection Trial) Study Group showed that HCV patients coinfected with HIV (N
= 868) treated with PEG-IFN alfa-2a (180 ug/week) plus RBV (800 mg/day) had a
higher rate of sustained virological response (SVR) (40%) than those given
interferon (IFN) alfa-2a (3 million IU [MU] 3 times weekly) plus RBV (12%;
p< 0.001) or PEG-IFN alfa-2a plus placebo (20%; p <0.001). Among patients
infected with HCV genotype 1, the SVR rates were 29%, 14%, and 7% in the
PEG-IFN alfa-2a plus RBV, IFN alfa-2a plus RBV, and PEG-IFN alfa-2a plus
placebo treatment groups, respectively. The frequency of adverse events was
similar to those previously reported in patients with HCV infection alone
undergoing therapy. In the second study, Raymond Chung and others from the AIDS
Clinical Trials Group randomized HCV patients coinfected with HIV to receive
RBV and either PEG-IFN alfa-2a 180 ug/weekly (n = 66) for 48 weeks or IFN
alfa-2a 6 MU 3 times weekly for 12 weeks followed by 3 MU 3 times weekly for 36
weeks (n = 67). The SVR rates were 27% for PEG-IFN-treated patients and 12% for
IFN-treated patients (p = 0.03). The authors also observed histological
responses to occur in 35% of patients who did not have a virologic response and
underwent a liver biopsy. The RIBAVIC study sponsored by a French national
research group is the third major trial that has only been published in
abstract form (11th Conference on Retroviruses and Opportunistic Infections [
Long-term follow-up of IFN treatment
of acute hepatitis C. Johannes Wiegand et al. report the outcomes of
31 patients who had acute HCV infection that was successfully treated with IFN
alfa-2b and were prospectively followed for a median of 135 weeks (range, 52-224
weeks) after the end of therapy. None of the patients were found to have
evidence of liver disease during follow-up. Serum ALT levels were normal in all
but one of the patients and serum assays for HCV RNA were negative. In
addition, HCV RNA was not detected in peripheral blood mononuclear cells of 15
cases tested. Anti-HCV levels decreased during and after IFN therapy in all
patients. HCV-specific CD8+ T-cell responses were observed in 4 of 5
HLA-A2-positive patients tested, while HCV-specific CD4+ T-helper cell
reactivity was detected in only 35% of patients. These findings demonstrated
that early IFN alfa-2b treatment of acute HCV infection resulted in long
lasting biochemical, virological, and clinical responses. The data also
suggested that T- and B-cell memory to HCV may be affected by IFN
treatment. (Wiegand J, et al. Hepatology 2004;40:98-107)
PRIMARY PROPHYLAXIS OF VARICEAL
BLEEDING
Variceal banding ligation (VBL)
versus propranolol (PPL) therapy. Michael Schepke and colleagues at
the
NONALCOHOLIC FATTY LIVER DISEASE
(NAFLD)
Role of adiponectin vs. tumor
necrosis factor (TNF)-α. Jason Hui and Australian colleagues
determined serum levels of adiponectin and TNF-α in 109 NAFLD patients (80
patients with NASH and 29 patients with simple steatosis). These serum markers
may play a role in NAFLD because adiponectin has anti-lipogenic and
anti-inflammatory effects and TNF-α reduces insulin sensitivity and has
pro-inflammatory effects. Multivariate analysis showed that patients with NASH
had reduced adiponectin serum levels and increased serum levels of TNF-α
and soluble TNF receptor 2 compared to controls matched for age, sex, and body
mass index. NASH patients also were
found to have lower adiponectin levels and increased insulin resistance (by
homeostasis model [HOMA-IR]) compared to patients with simple steatosis.
Furthermore, HOMA-IR and low serum adiponectin levels were associated with
increased grades of hepatic inflammation. These data suggested that a low serum
adiponectin level is a feature of NASH. An accompanying editorial by Mark Czaja
provides a brief review of the possible contributing roles that adiponectin and
inflammatory cytokines have in NAFLD and concludes that Hui et al. have
generated data supporting the concept that adiponectin is a potential therapy
for NAFLD. (Hui JM, et al. Hepatology
2004;40:46-54 and Czaja MJ. Hepatology
2004;40:19-22)
Hepatology Watch is produced through
educational grant from 
Hepatology Watch is a registered trademark of Market Development Group