Abstract

Hepatitis B has a complex natural history and causes a wide spectrum of disease. Population movements and immigration has changed the prevalence of the disease in Europe and elsewhere. Key steps in the replication of hepatitis B virus have been defined. Major patterns of chronic hepatitis have been defined. An inadequate innate and adaptive host immune response accounts for persistent infection, and immunological tolerance is evident in HBeAg positive patients with high viral loads. Several difficulties remain in formulating treatments for hepatitis B virus (HBV) infection; thus areas of disagreement exist. Current antiviral agents either inhibit hepatitis B replication, or invoke an immune response, which may be necessary but not sufficient to effect viral control. The end points of treatment are not clearly defined, and differ in HBeAg positive versus negative disease. Prolonged treatment for years is required for most patients. However, it is reasonable to infer improvement in disease outcome if HBV replication is suppressed with an accompanying improvement in serum ALT and hepatic necro-inflammatory disease. Two major groups of antiviral therapies are currently utilised. These include interferon alpha (IFN alpha (or pegylated interferon alpha, PEG IFN alpha) and nucleoside or nucleotide analogues. There are new nucleoside and nucleotides in the pipeline. Restoration or stimulation of the host immune response and clearance of infected hepatocytes occurs in only a small but critical proportion of HBeAg positive patients. These patients are more likely to lose HBeAg within one year. The continued use of single nucleotides in sequence, as in the past, may lead to the presence of multidrug resistant hepatitis B. Definitions of resistant mutations versus polymorphisms, and genotypic, phenotypic and clinical resistance remained incomplete. The efficacy of combination therapy has not been fully explored, but there could be looming disadvantages to using a monotherapy with drugs that induce high rates of resistance. At the present time clinicians, patients and public health authorities must make choices on basis of evidence that is not fully matured. However, considerable progress has been made in the development of potent and safe inhibitors of HBV, which have greatly facilitated the treatment of this disease.