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World J Gastroenterol. Jan 7, 2007; 13(1): 125-140
Published online Jan 7, 2007. doi: 10.3748/wjg.v13.i1.125
Antiviral therapy and resistance with hepatitis B virus infection
Hans L Tillmann
Hans L Tillmann, University of Leipzig, Philipp-Rosenthal Street 27, Leipzig 04103, Germany
Author contributions: All authors contributed equally to the work.
Supported by the German BMBF and Network for competence in viral hepatitis
Correspondence to: Hans L Tillmann, Professor of Medicine, University of Leipzig, Philipp-Rosenthal Street 27, Leipzig 04103, Germany.
Telephone: +49-341-9712231 Fax: +49-341-9712209
Received: September 11, 2006
Revised: September 25, 2006
Accepted: October 13, 2006
Published online: January 7, 2007

Hepatitis B virus (HBV) infection is still the most common cause of hepatocellular carcinoma and liver cirrhosis world wide. Recently, however, there has been quite dramatic improvement in the understanding of HBV associated liver disease and its treatment. It has become clear that high viral replication is a major risk factor for the development of both cirrhosis and hepatocellular carcinoma. Early studies have shown lamivudine lowers the risk of HBV associated complications. There are currently three nucleos(t)ides licensed, in addition to interferon, and there are more drugs coming to the market soon. Interferon or its pegylated counterpart are still the only options for treatment with defined end points, while nucleos(t)ides therapy is used mostly for long term treatment. Combination therapies have not been shown to be superior to monotherapy in naïve patients, however, the outcome depends on how the end point is defined. Interferon plus lamivudine achieves a higher viral suppression than either treatment alone, even though Hbe-seroconversion was not different after a one year treatment. HBV-genotypes emerge as relevant factors, with genotypes "A" and "B" responding relatively well to interferon, achieving up to 20% HBsAg clearance in the case of genotype "A". In addition to having a defined treatment duration, interferon has the advantage of lacking resistance selection, which is a major drawback for lamivudine and the other nucleos(t)ides. The emergence of resistance against adefovir and entecavir is somewhat slower in naïve compared to lamivudine resistant patients. Adefovir has a low resistance profile with 3%, 9%, 18%, and 28% after 2, 3, 4, and 5 years, respectively, while entecavir has rarely produced resistance in naïve patients for up to 3 years.

Keywords: Hepatitis B, Antiviral therapy, Resistance, Interferon, Nucleosides, Nucleotides