Management of Patients with Viral Hepatitis This book contains the manuscripts of the presentations from the 2nd International Conference on the Management of Patients with Viral Hepatitis, January 2007, Paris, France. Printed in January 2007 by the Nouvelle Imprimerie Laballery, 58500 Clamecy Print number : 611205, copyright : January 2007, printed in France Articles in this book can be cited as: In: Marcellin P, editor. Management of Patients with Viral Hepatitis. Paris: APHC; 2007. This book is supported by an unrestricted educational grant from F. Hoffmann-La Roche Ltd. © 2007 APHC, Paris, France Management of Patients with Viral Hepatitis Editor Patrick Marcellin Service d’Hépatologie Hôpital Beaujon University of Paris VII France CONTRIBUTING AUTHORS Alfredo Alberti Department of Clinical and Experimental Medicine and Venetian Institute of Molecular Medicine, University of Padova, Padova, Italy Bruce Bacon Division of Hepatology, St Louis University School of Medicine, St Louis, Missouri, USA Jason Bratcher Lenox Hill Hospital, New York, USA Michel Beaugrand Service d’Hépatologie, Hôpital Jean Verdier, Bondy, France Yves Benhamou Service d’Hépato-Gastroentérologie, Hôpital Pitié-Salpétrière, Paris, France Maria Buti Liver Unit, Hospital General Universitario Valle Hebron, Barcelona, Spain Stéphane Chevaliez French National Reference Center for Viral Hepatitis B, C and delta, Department of Virology & INSERM U635, Henri Mondor Hospital, University of Paris XII, Créteil, France Gary L. Davis Division of Hepatology, Baylor University Medical Center, Dallas, Texas, USA Yves Deugnier Clinique des Maladies du Foie, Hôpital Pontchaillou, University of Rennes, Rennes, France Douglas Dieterich Department of Medicine, Mount Sinai Medical Center, New York, USA Geoffrey Dusheiko Centre for Hepatology, Royal Free and University College School of Medicine, London, UK 1 Management of Patients with Viral Hepatitis, Paris, 2007 Rafael Esteban Liver Unit, Hospital General Universitario Valle Hebron, Barcelona, Spain Patrizia Farci Department of Medical Sciences, University of Cagliari, Cagliari, Italy Giovanna Fattovich Department of Gastroenterology, University of Verona, Verona, Italy Dominique Guyader Service des Maladies du Foie, Inserm U 522 and CIC Inserm 0203 Hôpital Pontchaillou, 35033 Rennes, France Chee-Kin Hui Department of Medicine, Queen Mary Hospital, The University of Hong Kong, Hong Kong SAR, China Stephanos J. Hadziyannis Department of Medicine and Hepatology, Henry Dunant Hospital and Hepatitis Research Laboratory of Athens University, Evgenidion Hospital, Athens, Greece Jenny Heathcote Toronto Western Hospital, University Health Network, University of Toronto, Toronto, Canada George L. K. Lau Division of Hepatology, Queen Mary Hospital, University of Hong Kong, Pokfulam, Hong Kong, China Anna S. F. Lok Division of Gastroenterology, University of Michigan Medical Center, Ann Arbor, Michigan, USA Patrick Marcellin Service d’Hépatologie and Inserm U 773, Hôpital Beaujon, University of Paris VII, Clichy, France Francesco Negro Division of Gastroenterology, University Hospital, Geneva, Switzerland Nicola Olivari Department of Surgical and Gastroenterological Science, Section of Gastroenterology, University of Verona, Italy 2 Contributing Authors Michela Pasino Department of Surgical and Gastroenterological Science, Section of Gastroenterology, University of Verona, Italy Jean-Michel Pawlotsky Department of Virology and INSERM U635, Henri Mondor Hospital, University of Paris XII, Créteil, France Robert P. Perrillo Division of Hepatology, Baylor University Medical Center, Dallas, Texas, USA Bruno Roche Centre Hépatobiliaire, Hôpital Paul Brousse, 14 Avenue Paul Vaillant Couturier, 94800 Villejuif, France Patrick Saitta The Mount Sinai Medical Center, New York, USA Didier Samuel Centre Hépatobiliaire, Hôpital Paul Brousse, Medical School of University of Paris XI, Villejuif, France Christoph Sarrazin Saarland University Hospital, Department of Internal Medicine II, Homburg, Germany Silvia Zanni Department of Surgical and Gastroenterological Science, Section of Gastroenterology, University of Verona, Italy Stefan Zeuzem Department of Internal Medicine II, Saarland University Hospital, Homburg, Germany Fabien Zoulim Service d’Hépato-Gastroentérologie and INSERM U271, Hôpital Hôtel Dieu, University of Lyon, Lyon, France 3 CONTENTS Hepatitis C and Hepatitis B in 2007 ............................................................ 7 P. Marcellin How to Use Virological Tools for the Optimal Management of Chronic Hepatitis C .................................................................................... 25 S. Chevaliez, J-M. Pawlotsky How to Predict the Outcome of Chronic Hepatitis C............................... 37 A. Alberti Fibroscan® in Patients with Chronic Viral Hepatitis............................... 43 M. Beaugrand What is the Optimal Treatment for Naïve Patients with Chronic Hepatitis C? .................................................................................. 49 S. Zeuzem, C. Sarrazin Clinical Case: Chronic Hepatitis C – Non-Responder to Pegylated Interferon and Ribavirin ............................................................................ 65 J. Heathcote How to Manage Patients with HIV/HCV Co-Infection............................ 73 J. Bratcher, P. Saitta, D. Dieterich Pre- and Post-Treatment of Liver Transplant Patients with Hepatitis C.......................................................................................... 95 D. Samuel, B. Roche Steatosis and HCV: Dangerous Liaisons?............................................... 111 F. Negro Alcohol in Chronic Hepatitis C: Legal or Prohibited? .......................... 119 G. L. Davis Iron and HCV: The Middle Age?............................................................ 131 Y. Deugnier, D. Guyader Clinical Case: Management of Patients with Chronic Hepatitis C...... 143 B. Bacon How to Use Virological Tools for the Optimal Management of Chronic Hepatitis B ................................................................................................. 149 F. Zoulim How to Predict the Outcome of Chronic Hepatitis B............................. 163 G. Fattovich, N. Olivari, M. Pasino, S. Zanni New Drugs for Chronic Hepatitis B......................................................... 179 M. Buti, R. Esteban 5 Management of Patients with Viral Hepatitis, Paris, 2007 Treatment of HBeAg-Positive Chronic Hepatitis B with Interferon or Nucleos(t)ide Analogs ............................................................................... 189 G. Dusheiko Why Treat Patients with HBeAg-Positive Chronic Hepatitis B with Pegylated Interferon? ............................................................................... 221 C-K. Hui, G. K. Lau Why Treat Patients with HBeAg-Negative Chronic Hepatitis B with Nucleos(t)ide Analogs? ............................................................................. 233 S. J. Hadziyannis Why Treat Patients with HBeAg-Negative Chronic Hepatitis B with Pegylated Interferon? ............................................................................... 245 R. P. Perrillo Management of HBV/HIV Co-Infection ................................................. 255 Y. Benhamou Treatment of Patients with Chronic Hepatitis Delta.............................. 263 P. Farci Clinical Case: Management of Antiviral-Resistant Hepatitis B........... 273 A. S. F. Lok 6 Hepatitis C and Hepatitis B in 2007 P. Marcellin INTRODUCTION Hepatitis B virus (HBV) and hepatitis C virus (HCV) infections are among the most frequent viral infections of man and represent a major global public health problem [1,2]. Hepatitis B virus- and HCV-related chronic hepatitis are the main causes of cirrhosis and hepatocellular carcinoma (HCC) which are responsible for a high rate of morbidity and mortality. End-stage HBV- and HCV-related liver disease and HCC are the main causes of liver transplantation. In the last few years, knowledge of the epidemiology and natural history of HBV and HCV infection has markedly improved. Furthermore, considerable progress has been made in the efficacy of therapy. New drugs and new therapeutic strategies which are currently under evaluation could further improve the efficacy of therapy in the near future. HEPATITIS B Epidemiology Approximately one third of the world’s population has serological evidence of past or present infection with HBV and 350 million people are chronically infected. The prevalence of HBV infection is especially high in South-East Asia and Sub-Saharan Africa where more than 8% of the population are chronic hepatitis B surface antigen (HBsAg)-carriers [3]. While perinatal transmission or transmission during early childhood are responsible for the high rate of chronic 7 Management of Patients with Viral Hepatitis, Paris, 2007 infection in Asia and Africa, sexual or parenteral exposure account for most cases in industrialized countries [4]. In most developed parts of the world, the prevalence of chronic HBV infection is less than 1%, and the overall infection rate is 5 to 7%. Within these areas most infections occur among high-risk adult populations that include injection drug users, persons with multiple heterosexual partners, men who have sex with men, and healthcare workers. The risk of perinatal HBV transmission has been well described. This risk is greatest for infants born to women who are hepatitis Be antigen (HBeAg)-positive and ranges from 70 to 90% at 6 months of age; about 90% of these children