Genetic variants of hepatitis B virus and their clinical relevance.
Infection with hepatitis B virus (HBV) leads to a wide spectrum of clinical presentations ranging from an asymptomatic carrier state to self-limited acute or fulminant hepatitis to chronic hepatitis with progression to cirrhosis and hepatocellular carcinoma (HCC). Infection with HBV is one of the most common viral diseases affecting man. Both viral factors as well as the host immune response have been implicated in the pathogenesis and clinical outcome of HBV infection. Evidence has been accumulating that HBV mutants are associated with certain clinical disease manifestations, may affect the natural course of the infection and confer resistance to antivirals. Naturally occurring mutations have been identified in the structural and non-structural genes as well as regulatory elements of the virus. The best characterized mutants comprise the pre-core (pre-C) stop codon mutation resulting in a loss of hepatitis B e antigen (HBeAg), defined clusters of mutations in the core promotor resulting in enhanced viral replication and mutations in the hepatitis B core and surface antigens (HBcAg and HBsAg) altering the antigenicity of the virus. More recently, several mutations in the reverse transcriptase/polymerase gene have been identified conferring resistance to antivirals used for the treatment of chronic hepatitis B. In this review, we will focus on the biological phenotype of HBV genetic variants and discuss their clinical relevance for the pathogenesis of HBV-induced liver disease.
Baumert
T F
TF
Department of Medicine II, University of Freiburg, Freiburg, Germany.
Barth
H
H
Blum
H E
HE
D000998:Antiviral Agents / Q000494:pharmacology; D003062:Codon; D024882:Drug Resistance, Viral; D005814:Genes, Viral; D014644:Genetic Variation; D006509:Hepatitis B / Q000188:drug therapy / Q000276:immunology / Q000503:physiopathology / Q000821:virology*; D006512:Hepatitis B Core Antigens / Q000032:analysis; D006515:Hepatitis B virus / Q000187:drug effects / Q000235:genetics*; D006801:Humans; D009154:Mutation; D010641:Phenotype; D011401:Promoter Regions, Genetic
D000998:Antiviral Agents; D003062:Codon; D006512:Hepatitis B Core Antigens