Virological and Clinical Characteristics of Hepatitis B Virus Genotype A

Hepatitis B virus (HBV) infection is one of the most prevalent chronic viral infections in humans. The overall prevalence of hepatitis B surface antigen (HBsAg) is reported to be 3.6%; however, it varies depending upon the geographic area. HBV is classified into ten genotypes (A through J) on the basis of an intergroup genomic divergence of > 8%. Specifically, HBV genotype A exhibits several unique virological and clinical characteristics and can be further classified into seven subtypes. Among them, subtype A2 or Ae (A2/[e]) is occasionally responsible for nosocomial infection and among homosexual males. Regarding virological factors, the G1896A precore mutation is rarely observed in genotype A as it would disrupt an essential stem-loop structure in the ε signal essential for pregenomic RNA packaging. HBV genotype A also harbors a 6-nucleotide C-terminal insertion in the hepatitis B-e antigen (HBeAg) precursor, resulting in a variable-length HBeAg protein product observed in serum of positive patients. These molecular traits likely contribute to the specific clinical presentation of genotype A-infected patients, such as mild acute hepatitis B (AHB), longer persistence of HBsAg positivity in AHB, and increased chronicity after AHB in adults. However, genotype A shows a better response to interferon than other genotypes in chronic hepatitis B patients. Here, we review the virological and clinical characteristics of HBV genotype A that will be useful in elucidating the association among persistent viral infection, host genetic factors, and treatment in future studies.