IMMUNOPATHOGENESIS OF HEPATITIS B VIRUS INFECTION

Abstract

Hepatitis B virus (HBV) is a hepatotropic, enveloped, partially double-stranded DNA virus that causes acute and chronic hepatitis. It has been estimated that over 300 million people are chronically infected with HBV throughout the world.26, 56 HBV infection in adults usually is self-limited and subclinical, resulting in chronic infection in only 5% to 10%.23 Neonatal transmission of HBV, however, results in chronicity in over 90%, accounting for most infections observed in Asia and Africa.23 Chronic HBV infection is associated with a varying degree of disease severity, ranging from clinically inapparent healthy carriers to severe chronic active hepatitis that may progress to cirrhosis and hepatocellular carcinoma (HCC). In particular, the lifetime risk of HCC may be as high as 40% for men infected at birth.5 Although an effective vaccine does exist, a large number of patients already are chronically infected and suffer from the associated complications. Currently, interferon (IFN) αtherapy results in sustained viral clearance in only one-third of HBV-infected patients.49 Other antiviral drugs, such as lamivudine, display only temporary suppression of virus replication during the duration of therapy but not after cessation of therapy.28 The pathogenetic mechanisms responsible for the development of acute and chronic hepatitis, cirrhosis, and HCC in patients with HBV infection are defined only partially because of the limited host range and lack of an in vitro culture system or an easily manipulable small animal model of HBV infection. HBV does not appear to be highly cytopathic in most instances.25 Both humoral and cellular immune responses are needed for viral clearance, whereas the cellular response also may be involved in disease pathogenesis. Recent data support a noncytolytic mechanism of viral clearance mediated by antiviral cytokines (e.g., IFNγ, tumor necrosis factor [TNF]α, and interleukin [IL]2) produced by activated macrophages and T cells.18, 41, 42, 43 This review addresses the role of the antiviral immune response in the outcome of human HBV infection.