EmergingdrugsforhepatitisB创新.docVIP

Emerging drugs for hepatitis B Fabien Zoulim 1,2,3 1 INSERM, U871, Molecular Pathobiology and New Treatments of Viral Hepatitis, Lyon, F-69003, France. 2 Université Lyon 1, IFR 62 Lyon Est, Lyon, F-69008, France 3 Hospices civils de Lyon, H?tel Dieu, Department of Liver Diseases, Lyon, F-69002, France Address for correspondence Fabien Zoulim INSERM U871, 151 cours Albert Thomas, 69424 Lyon cedex 03, France. Phone: (+33)-472681970, Fax : (+33)-472681971. E-mail address: zoulim@lyon.inserm.fr Acknowledgements F. Zoulim receives grant from INSERM and the European Community (VIRGIL Network of Excellence, grant LSHM-CT-2004-503359). Abstract Chronic hepatitis B remains a treatment challenge despite the availability of new nucleoside analogs. This is due to the persistence of viral infection during therapy, which exposes the patient to the risk of developing antiviral drug resistance. Therefore, new polymerase inhibitors are needed to manage resistance to currently available drugs and to design new trials of combination therapy to delay drug resistance. In the future, antiviral agents targeting other steps of the viral life cycle will be needed to achieve antiviral synergy and prevent antiviral drug resistance. Immune modulators are also expected to enhance antiviral response and to achieve sustained response. Discovery of new antiviral drugs and design of new treatment strategies are therefore needed to manage this disease which is still the main cause of cirrhosis and hepatocellular carcinoma worldwide. Keywords?: hepatitis B, nucleoside analogs, polymerase inhibitors, viral resistance, chronic hepatitis I. Background Chronic hepatitis B virus infections remain a major public health problem worldwide. The main clinical outcome is the development of chronic hepatitis, followed by liver cirrhosis and hepatocellular carcinoma. HBV is the first cause of hepatocellular carcinoma world wide (1, 2). HBV replication does not induce directly a cytopathic effect, liver damage