Hepatitis B Virus

Abstract

Abstract Human hepatitis B virus (HBV) is the prototype member of the Hepadnaviridae family of viruses, characterised by a relaxed circular, ∼3200‐bp deoxyribonucleic acid (DNA) genome (rcDNA) with replication primarily in hepatocytes, the major parenchymal cell of the liver. HBV infections may be transient or chronic. All hepadnaviruses, including those that infect humans as well as small animal species, are similar clinically and biologically. Part of the replication strategy includes conversion of the rcDNA genome into covalently closed circular DNA (cccDNA), which is found exclusively in the nucleus of infected hepatocytes. This cccDNA acts as template for the transcription of all hepadnaviral messenger ribonucleic acids (mRNAs). One of the largest mRNAs, the pregenome, is reverse transcribed in the cytoplasm into new rcDNA. cccDNA is a highly stable molecule present as a mini chromosome with up to 10–50 copies in the nucleus of each infected hepatocyte. The stability of cccDNA, the noncytolytic nature of infection and the fact that hepatocytes constitute a self‐renewing population make chronic HBV infections difficult to treat. The natural course of chronic HBV infection consists of four phases: immune tolerance, immune clearance, immune control and reactivation and is associated with liver disease that encompasses a wide range of histological changes. Key Concepts: There are two possible outcomes of HBV infection: transient or chronic infection. Transient (acute) HBV infections often spread to infect >95% of hepatocytes and can be rapidly cleared from the liver. Ninety to ninety‐five percent of adults experience transient infections, whereas 30–90% of children develop chronic HBV infections. Chronic HBV infection can result in liver disease including portal and lobular inflammation, fibrosis, cirrhosis and hepatocellular carcinoma (HCC). Multiple copies of cccDNA are present in each infected hepatocyte and act as a stable reservoir for HBV infection. The highly stable nature of cccDNA is the major factor in the failure of antiviral therapy during chronic HBV infection. Pre‐exposure vaccination with HBV surface antigen (HBsAg) particles results in an anti‐HBs antibody response that provides immunity against HBV infection. HBV remains a major worldwide problem with >360 million people with chronic infection.