|
Ira S. Goldman, MD; John L. Gollan, MD, PhD; Kris V. Kowdley, MD; Paul Martin, MD;
Marion G. Peters, MD |
|
HEPATOLOGY WATCH® |
FEBRUARY 2004
HEPATITIS B VIRUS (HBV) INFECTION
Adefovir dipivoxil (ADV) alone or in combination. In a recent open-label,
multicenter study, Eugene Schiff et al showed that 48 weeks of ADV monotherapy
given to pre- and post-liver transplantation patients with evidence of
lamivudine (LAM)-resistant HBV (N = 324) resulted in a significant virological
response rate and improvements in biochemical and clinical parameters. Fabien Zoulim concluded in an accompanying
editorial that these data confirm the results of previous pilot studies and
that combination nucleoside/nucleotide therapy needs to be evaluated because
the long-term emergence rate of ADV-resistant strains is not known. Robert Perrillo and others found that the
addition of ADV to LAM in patients with YMDD mutant HBV was well tolerated and
was associated with virological and biochemical improvements during 52 weeks of
treatment. In addition, Marion Peters
and colleagues conducted a randomized trial in 59 patients with compensated
liver disease and demonstrated that ADV alone or in combination with continued
LAM therapy provided effective treatment for patients with LAM-resistant
HBV. In an editorial, Tim Shaw et al.
cautioned that although these 2 studies confirmed the activity of ADV against
LAM-resistant HBV, there is little evidence to suggest that LAM adds clinical
benefit when combined with ADV. They
suggest that long-term prevention of resistant HBV mutations may require the
addition of different classes of antiviral agents to combination nucleoside/nucleotide
drug therapy. (Schiff ER, et al. Hepatology 2003;38:1419-1427; Zoulim F. Hepatology 2003;38:1353-1355; Perrillo
R, et al. Gastroenterology
2004;126:81-90; Peters MG, et al. Gastroenterology
2004;126:91-101; and Shaw T, et al. Gastroenterology
2004;126:343-350)
Preemptive lamivudine therapy for HBsAg-positive cancer
patients. Reactivation
of HBV is a serious cause of morbidity and mortality in HBsAg-positive cancer
patients undergoing chemotherapy. George
Lau and coworkers randomized 30 consecutive patients with lymphoma undergoing
intensive chemotherapy to initiate LAM 100 mg daily either preemptively 1 week
prior to the start of chemotherapy (group 1) or when there was serologic
evidence of HBV reactivation (group 2).
Eight (53%) patients in group 2 and none of the patients in group 1 had
HBV reactivation after chemotherapy. The
period of survival free from hepatitis due to HBV reactivation was longer for
group 1 compared to group 2 patients (p = 0.002). These results indicated that preemptive LAM
therapy more effectively prevented the development of hepatitis than deferred
LAM treatment in HBsAg-positive lymphoma patients undergoing chemotherapy. (Lau GKK, et al. Gastroenterology 2003;125:1742-1749)
HEPATITIS C VIRUS (HCV) INFECTION
Inadequate biopsies give inadequate information. Pierre Bedossa and colleagues
evaluated the sampling variability of fibrosis in surgical liver biopsies from
patients with chronic HCV infection.
Measurements of fibrosis were performed on the whole section utilizing
both image analysis and METAVIR score.
Their findings suggested that a length of at least 25 mm is necessary to
evaluate fibrosis accurately from a liver biopsy specimen. (Bedossa P, et al. Hepatology 2003;38:1449-1457)
HCV prevalence in B-cell non-Hodgkin's lymphoma
(B-NHL). Javier
Gisbert et al performed a meta-analysis of 48 case-control studies comparing
the prevalence of HCV infection in patients with B-NHL to that of a reference
group. The overall mean HCV infection
prevalence was 13%. HCV prevalence was
higher in
Effect of highly active antiretroviral therapy (HAART) on
liver-related mortality. HAART is
associated with hepatotoxicity and does not inhibit HCV replication. To assess the effect of HAART in patients
coinfected with HIV and HCV, Nazifa Qurisha and others at the
Signal transduction pathways. Intracellular signaling cascades
are inhibited by HCV. For example, HCV
NS3 protease blocks the phosphorylation and effector action of interferon (IFN)
regulatory factor 3 (a key cellular antiviral signaling molecule). The reduction of HCV RNA plasma levels
observed in early studies of BILN 2061, a small molecule inhibitor of NS3
protease, provides a proof-of-concept for targeted therapy. Recent studies in hepatocytes obtained from
liver biopsies of HCV patients indicate that perturbation of the Jak-STAT
signaling pathway interferes with IFN-a signaling resulting in reduced transcriptional
activation of IFN-a
stimulated genes. These findings
indicate the potential for a viral enzyme-targeted drug discovery
approach. (Lamarre D, et al. Nature 2003;426:186-189; Foy E, et al. Science 2003;300:1145-1148; and Duong
FHT, et al. Gastroenterology 2004;126:263-277)
Hepatology Watch is produced through
educational grant from 
Hepatology Watch is a registered trademark of Market Development Group