R E V I E W The role of entecavir in the treatment of chronic hepatitis B Evangelini Dimou Vasilios Papadimitropoulos Stephanos J Hadziyannis Department of Medicine and Liver Unit, Henry Dunant Hospital, Athens, Greece Correspondence: Stephanos J Hadziyannis Department of Medicine and Liver Unit, Henry Dunant Hospital, 107 Messogion Ave, 11526 Athens, Greece Tel +30 210 697 2937 Fax +30 210 697 2974 Email hadziyannis@ath.forthnet.gr Abstract: Entecavir (ETV) is a potent and selective inhibitor of hepatitis B virus replication. In HBeAg-positive and HBeAg-negative lamivudine-naïve patients with chronic hepatitis B (CHB), treatment with ETV at a dose of 0.5 mg daily is associated with a more potent viral suppression, a higher rate of biochemical remission and a greater improvement of liver histology compared to Lamivudine (LAM). After 3 years of ETV treatment, the majority of patients (94%) may achieve serum HBV DNA levels undetectable by sensitive PCR assays. ETV treatment of patients with LAM-resistant HBV mutants requires a higher daily dose of 1 mg yet, potent HBV suppression at 3 years is achieved only in 40% of them while the cumulative rate of genotypic HBV resistance increases from 6% in the ﬁrst year to 30% in year 3. ETV resistance of HBV is rare in lamivudine-naïve patients with a reported rate of 1% after three years of treatment. In conclusion, ETV is a very potent anti-HBV drug with a high genetic barrier to resistance, highly effective in lamivudine-naïve CHB patients and most promising for their long-term treatment but not very suitable for CHB patients harboring LAM–resistant HBV mutants. Keywords: entecavir, chronic hepatitis B, nucleoside analogue, HBV resistance Introduction Chronic hepatitis B virus (HBV) infection is a major health problem, affecting hundreds of millions of people worldwide. It may progress to cirrhosis and hepato- cellular carcinoma (HCC) and is responsible for almost 1 million deaths annually (Lee 1997; Maddrey 2000). Eradication of HBV infection with currently available therapies is not really possible. Resolution of the infection, as indicated by HBsAg loss and development of anti-HBs, is also extremely rare. Thus, the most realistic goal of hitherto approved therapies for chronic hepatitis B (CHB) is potent and durable sup- pression of viral replication aiming at stop of progression and remission/regression of the underlying liver disease (Di Marco et al 2004; Liaw et al 2004). More speciﬁcally, in patients with HBeAg-positive CHB the end point and goal of treatment is HBeAg seroconversion, while in patients with HBeAg-negative CHB is durable suppression of HBV to HBV DNA levels undetectable by real time PCR assays (Lok et al 2001). Six drugs have been approved for the treatment of chronic hepatitis B, standard interferon-α (IFN-α), the Pegylated form (PEG)-IFN-α-2a, and the nucleos(t)ide analogues Lamivudine (LAM), Adefovir Dipivoxil (ADV), Entecavir (ETV) and most recently Telbivudine (LdT). Interferon-alpha Interferon-alpha is the ﬁrst drug approved for the treatment of CHB. In HBeAg- positive CHB ﬁnite course of treatment with standard IFN-α has achieved HBeAg loss in 33% of treated patients vs 12% of placebo-treated controls, p = 0.0001 (Wong et al 1993), with responses being durable after stopping treatment (Nie- deraou et al 1996). In HBeAg-negative CHB, long-term biochemical remission Therapeutics and Clinical Risk Management 2007:3(6) 1077–1086 © 2007 Dove Medical Press Limited. All rights reserved 1077