Precore mutations and core clustering mutations in chronic hepatitis B virus infection.

Abstract

Mutant hepatitis B virus is often associated with severe liver damage. The purpose of this study is to elucidate the relationship between mutations in hepatitis B precore/core gene and the severity of liver damage. The hepatitis B precore/core gene from 20 patients with chronic hepatitis B virus infection was studied by polymerase chain reaction and direct sequencing. Missense mutations in the core gene were only found in patients with chronic active hepatitis. Three mutation clustering regions of core gene, codons 48-60, 84-101, and 147-155, had higher substitution rates than other regions. All patients with chronic active hepatitis had missense mutation(s) either in codons 84-101 or in codons 48-60. There was a trend of increasing substitutions in the precore/core gene from e antigen-positive asymptomatic carriers to e antibody-positive patients with chronic active hepatitis. These data suggest that (1) severe liver damage in chronic hepatitis B virus infection is related to the clustering missense mutations in codons 48-60 and 84-101 of core gene and that (2) the emergence of precore stop codon mutation and missense mutations around the carboxy-terminal processing site of precore/core protein (codons 147-155) may be the adaptive mechanisms of hepatitis B virus to decrease production and secretion of viral protein and retain the viral persistence.