Mutants in the precore, core promoter, and core regions of Hepatitis B virus, and their clinical relevance

Molecular virology methods including polymerase chain reaction, sequencing and cloning were a revolution in our understanding about the viral genomes. In the case of hepatitis B virus (HBV), sequencing studies have resulted in the identification of a number of virus variants normally found during the natural course of infection, or arising as a result of medical intervention. Examples are the precore and the basic core promoter (BCP) variants, others affecting the enhancer II (EnII) region, as well as various deletion variants found in immunocompromised individuals. The appearance of precore/ core gene and BCP variants heralds the initiation of the seroconversion phase from HBeAg to anti-HBe. The above variants have been studied in detail in different settings of HBV infection such as acute or fulminant hepatitis, chronic hepatitis with high viremia levels and in immunocompromised individuals. The existence of the variants was associated with the clinical severity, prognosis of liver disease and the response to treatment. However, the mechanisms of their selection and clearance remain to be defined.