General Knowledge of Medical Therapy of HB

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Interferon a-2b is the only FDA-approved interferon product for hepatitis B. The recommended dose is 5 million units subcutaneously 5 times per week for 4 months associated and this has been with histological benefit primarily in patients with loss of serum HBeAg. However, most patients do not have loss of HBeAg or HBsAg (Figure 9). Recently, the FDA approved a synthetic nucleoside analog, lamivudine (Epivir-HBV™ for use in patients with chronic HBV infection associated with evidence of hepatitis B viral replication and active liver inflammation. Lamivudine inhibits HBV polymerase reverse transcriptase activity resulting in chain termination of nascent HBV DNA strands. It has also been shown to have activity against human immunodeficiency virus (HIV). Preclinical studies show a satisfactory safety profile with no evidence of mutagenicity, carcinogenicity, or teratogenic potential. It leads to dose-related reduction in HBV DNA levels after oral absorption with an equimaximal effect at doses greater than 100 mg/day. In large placebo-controlled clinical trials, lamivudine therapy for 52 weeks produced a significantly greater frequency of histological responses (55% vs. 25%, compared with placebo treatment) defined as > 2 point decrease in Hepatic Activity Index (HAI) score. Lamivudine also significantly enhanced the proportion of patients (17% vs. 6% when compared with placebo treatment) undergoing a three-component HBeAg seroconversion (HBeAg-, HBeAb+, HBV DNA-). However, the ideal duration of treatment is not known. Discontinuation of therapy may lead to recurrence of HBV DNA and possibly a “rebound” alanine aminotransferase elevation. In addition, 27% of patients may become resistance to “YMDD” mutations after 52 weeks of therapy. This illustrates the complexity of treatment for chronic HBV infection and demonstrates the need for future treatment regimens that solve these issues. Indeed, combination treatment with lamivudine and interferon appears to improve patient outcomes in preliminary studies. Finally, a comparison of multiple drug combinations (HBV “cocktails” vs. sequential nucleoside analogs, e.g., adefovir, famciclovir, etc.) will need to be performed to determine the best long-term treatment strategies for chronic hepatitis B infection. Liver transplantation remains an option for those who progress to end-stage liver disease. Indeed, survivial rates have increased and recurrence rates of HBV have declined since the institution of long-term hepatitis B immune globulin after liver transplantion. The availability of nucleoside analogs may further improve outcomes in the post-transplantation period. [ This page was updated by awei on 2001-12-14.00:21:19. ]