Hepatitis

Journal of Hepatology 50 (2009) 227–242 www.elsevier.com/locate/jhep

EASL Clinical Practice Guidelines: Management of chronic hepatitis B
European Association for the Study of the Liver*

Keywords: Hepatitis B virus; EASL guidelines; Treatment; Interferon alpha; Nucleoside/nucleotide analogues

1. Introduction Our understanding of the natural history of hepatitis B virus (HBV) infectionand the potential for therapy of the resultant disease has improved. Several new and effective antiviral agents have been evaluated and licensed since the EASL International Consensus Conference on hepatitis B held in 2002 [1]. The objective of these EASL Clinical Practice Guidelines (CPGs) is to update recommendations for the optimal management of chronic hepatitis B (CHB). The CPGs do not focus onprevention and vaccination. Several difficulties remain in formulating treatments for CHB; thus areas of uncertainty exist. At the present time clinicians, patients and public health authorities must continue to make choices on the basis of evidence that is not fully matured. 2. Context 2.1. Epidemiology and public health burden Approximately one third of the world’s population has serologicalevidence of past or present infection with HBV and 350 million people are chronically infected. The spectrum of disease and natural history of chronic HBV infection is diverse and variable, ranging from a low viremic inactive carrier state to progressive chronic hepatitis, which may evolve to cirrhosis and hepatocellular carcinoma (HCC). HBV-related end stage liver dis-

ease or HCC are responsiblefor over 1 million deaths per year and currently represent 5–10% of cases of liver transplantation [2–5]. Host and viral factors, as well as coinfection with other viruses, in particular hepatitis C virus (HCV), hepatitis D virus (HDV), or human immunodeficiency viru s (HIV) together with other co-morbidities including alcohol abuse and overweight, can affect the natural course of HBV infection aswell as the efficacy of antiviral strategies. CHB may present either as hepatitis B e antigen (HBeAg)-positive or HBeAg-negative CHB. HBeAgpositive CHB is due to so-called ‘‘wild type” HBV. It typically represents the early phase of chronic HBV infection. HBeAg-negative CHB is due to replication of naturally occurring HBV variants with nucleotide substitutions in the precore and/or basic corepromoter regions of the genome and represents a later phase of chronic HBV infection. The prevalence of the HBeAgnegative form of the disease has been increasing over the last decade as a result of HBV-infected population aging and represents the majority of cases in many areas, including Europe [6–8]. Morbidity and mortality in CHB are linked to persistence of viral replication and evolution tocirrhosis or HCC. Longitudinal studies of patients with CHB indicate that, after diagnosis, the 5-year cumulative incidence of developing cirrhosis ranges from 8 to 20%. The 5-year cumulative incidence of hepatic decompensation is approximately 20% with the 5-year probability of
Contributors: Clinical Practice Guidelines Panel: Patrick Marcellin, Geoffrey Dusheiko, Fabien Zoulim, Rafael Esteban, StefanosHadziyannis, Pietro Lampertico, Michael Manns, Daniel Shouval, Cihan Yurdaydin; Reviewers: Antonio Craxi, Xavier Forns, Darius Moradpour, Jean-Michel Pawlotsky, Joerg Petersen, Heiner Wedemeyer.

EASL office, 7 rue des Battoirs, CH 1205 Geneva, Switzerland. Tel.: +41 22 807 0360; fax: +41 22 328 0724. E-mail address: easloffice@easloffice.eu

*

0168-8278/$34.00 Ó 2009 Published by Elsevier B.V.on behalf of the European Association for the Study of the Liver. doi:10.1016/j.jhep.2008.10.001

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European Association for the Study of the Liver / Journal of Hepatology 50 (2009) 227–242

survival being approximately 80–86% in patients with compensated cirrhosis [4,9–13]. Patients with decompensated cirrhosis have a poor prognosis with a 14–35% probability of survival at 5 years. The...