Novel targets for hepatitis B virus therapy

Abstract

Treatment with either pegylated interferon- alpha (peg IFN – α) or last generation nucleos(t)ide analogues ( NA s) successfully leads to serum viral load suppression in most chronically infected hepatitis B ( CHB ) patients, but HB sAg loss is only achieved in 10% of the cases after a 5- year follow- up. Thus, therapy must be administered longterm and it will not completely eliminate infection because of the persistent hepatitis B virus ( HBV ) minichromosome in infected cells, and cannot completely abolish the risk of developing severe sequelae such as cirrhosis and hepatocellular carcinoma. Recent progress in the development of in vitro and in vivo models of HBV infection have helped renew interest in the investigation of the viral life cycle, as well as specific virus–host cell interactions to identify new targets for the development of new antiviral drugs. This includes either direct inhibition of viral replication by targeting fundamental steps such as entry, ccc DNA formation/stability, viral transcripts, capsid assembly and secretion or the manipulation of the host immune system for better defence against infection. Multiple strategies are currently under investigation, including boosting endogenous innate responses and/or restoring adaptive immunity via engineering of HBV – specific T cells or via the use of inhibitors of negative regulators, as well as therapeutic vaccines. It is increasingly clear that multiple therapeutic strategies must be combined to reach a cure of HBV and that the definition of clinical, virological and immunological correlates for the management of treatment are urgently needed.

 

K E Y W O R D S
hepatitis B virus , immunotherapy , viral targets

About Speaker

Fabien ZOULIM

Professor of Medicine, Lyon University, Institut Universitaire de France // Medical Director, Hepatology Department at the Hospices Civils de Lyon, France // Scientific Director, Viral Hepatitis Research Laboratory, INSERM U1052, Cancer Research Center of Lyon, France

France

City: Lyon

Institution: Lyon University and INSERM


Biography of Fabien ZOULIM

Fabien Zoulim obtained his M.D. in Gastroenterology and Hepatology in Lyon Medical School in 1991. He has also obtained a PhD in Molecular and
Cellular Biology and was trained as a post-doctoral researcher at Fox Chase Cancer Center in Philadelphia. He is Professor of Medicine at LyonUniversity since 1997. He is currently Medical Director of the Hepatology Department at the Hospices Civils de Lyon, and Scientific Director of the Department of Immunology and Virology of INSERM Unit 1052 where he is leading the team on ‘Antiviral therapy of viral hepatitis’. Dr Zoulim has served as an Associate Editor for Journal of Hepatology and is currently Associate Editor for Gut. He also served as an expert in the microbiology study section of the INSERM and as head of the clinical viral hepatitis study section at ANRS. He served as a Governing Board member of the European Association for the Study of the Liver (EASL). Dr Zoulim received the William Prusoff award of the International Society for Antiviral Research. Furthermore, he has been the scientific coordinator of a European community-funded Network of Excellence on the management of antiviral drug resistance, and is currently head of the ANRS “HBV cure” program in France. He co-founded the International Coalition to Eliminate HBV (ICE-HBV: http//:www.ice-hbv.org). Fabien Zoulim is a recognized expert in the field of viral hepatitis and antiviral therapy, and has published more than 400 articles (H index 72, Web of Science).

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