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

Background: 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. Methods: The hepatitis B precore/ core gene from 20 patients with chronic hepatitis B virus infection was studied by polymerase chain reaction and direct sequencing. Results: 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 antigenpositive asymptomatic carriers to e antibody-positive patients with chronic active hepatitis. Conclusions: 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.