Natural Course, Therapeutic Options and Economic Evaluation of Therapies for Chronic Hepatitis B

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作者：Dr Steven-Huy B. Han (1)
刊名：Drugs
出版年：2006
出版时间：October 2006
年：2006
卷：66
期：14
页码：1831-1851
全文大小：160KB
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作者单位：Dr Steven-Huy B. Han (1) 1. David Geffen School of Medicine at UCLA, Pfleger Liver Institute, 200 Medical Plaza, Suite 214, Los Angeles, California, 90095-7302, USA

文摘

Chronic hepatitis B virus infection afflicts 400 million people worldwide and untreated will progress to cirrhosis in 15-0% of individuals, with an associated increased risk for the development of hepatocellular carcinoma. The ‘inactive carrier state-carries a benign prognosis with a very low risk of cirrhosis or hepatocellular carcinoma. However, the hepatitis B e antigen (HBeAg)-positive chronic hepatitis state is an active disease state with increased risk for progressing to cirrhosis and hepatocellular carcinoma. The HBeAg-negative mutant variety of chronic hepatitis B has been associated with a higher incidence of cirrhosis at initial presentation and more frequent progression to hepatocellular carcinoma compared with the wild-type hepatitis B. Five medications are currently approved by the US FDA for the treatment of chronic hepatitis B: interferon-α, lamivudine, adefovir dipivoxil, entecavir and peginterferon-α-2a. Interferon-α therapy has been shown to increase the rate of HBeAg and hepatitis B DNA loss with a small chance of hepatitis B surface antigen loss, but has significant adverse effects and is ineffective against the HBeAg-negative mutant. Lamivudine is a safely used, orally administered drug with good efficacy, but is associated with the development of a lamivudine-resistant (Lam-R) mutant in a large proportion of patients after long-term therapy. High relapse rates after lamivudine therapy make this medication less effective in the HBeAg-negative mutant also. Adefovir dipivoxil is a safely used, orally administered drug, which is effective against the Lam-R mutant. Adefovir dipivoxil is effective against the wild-type and HBeAg-negative hepatitis B and has a very low incidence of resistance development. Entecavir is a highly potent and selective new oral drug against hepatitis B. It has demonstrated no resistance development in treatment-naive patients, but a low incidence of resistance in patients infected with prior Lam-R mutants. Peginterferon-α-2a is administered once weekly and has improved efficacy compared with standard interferon-α and lamivudine. However, it has a similar adverse-effect profile to standard interferon-α. Pharmacoeconomic studies have demonstrated a cost benefit in treating chronic hepatitis B patients compared with no therapy. However, results have been conflicting, with earlier studies showing a cost advantage of lamivudine over interferon-α and a more recent, comprehensive study favouring interferon-α monotherapy in HBeAg-negative patients and adefovir dipivoxil ‘salvage-after lamivudine resistance development in HBeAg-positive patients.

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