Hepatitis B: Where Are We Today?

Abstract

Hepatitis B still is a major challenge of modern medicine. Here, we summarize the disease, the life cycle of the virus, the emergence of drug-resistant mutant strains and resulting consequences for new drug development. Hepatitis B has a worldwide prevalence of 0.1-20%. It occurs in an acute and a chronic phase. The acute phase is characterized by viral replication, onset of immune response leading to destruction of infected hepatocytes and, in most cases, viral clearance and lifelong immunity. Clinical symptoms are observed in this phase. The chronic phase is characterized by lifelong persistence of the virus, often without clinical symptoms but bearing the risk of hepatic cirrhosis or hepatocellular carcinoma. Both phases are distinguished by detection of viral antigens and hepatitis B antibodies in the blood. The hepatitis B virus (HBV) shows several features unique for hepadnaviridae: i) formation of covalently closed-circle DNA (cccDNA) as template for viral DNA replication and synthesis of viral RNAs and ii) a reverse transcription step in the synthesis of new viral DNAs. These features are the prime targets in antiviral drug development. Unfortunately, with the exception of interferon, resistant mutant strains of HBV were found after widespread use of every new drug so far. Therefore, combination therapies aimed at different targets are being discussed so that the selective pressure can no longer be compensated by HBV. This paper is the first part of a trilogy concerning HBV which will also discuss the situation regarding transplantation (second part) and blood transfusion (third part).