Rapid Publication Variations in Codons 84-101 in the Core Nucleotide Sequence Correlate with Hepatocellular Injury in Chronic Hepatitis B Virus Infection

Individuals with chronic hepatitis B virus (HBV) infection are generally divided into asymptomatic healthy carriers and pa-tients with chronic liver disease. Several studies have suggested that the hepatitis B core antigen could be an immunological target of cytotoxic T lymphocytes (CTL). To investigate the possible pressure site from CGL, the entire core region ofHBV DNA was sequenced in 30 subjects (10 asymptomatic healthy carriers and 20 patients with chronic liver disease). No signifi-cant changes in the nucleotide sequence and deduced amino acid residue were noted in the 10 healthy carriers. In contrast, a cluster of changes in a small segment of 18 amino acids (codons 84-101 from the start of the core gene) was found in 15 of the 20 chronic liver disease patients. All these 15 patients had ad-vanced liver diseases (chronic active hepatitis and cirrhosis), whereas only mild liver disease (chronic persistent hepatitis) was found in the five patients without mutations. These data suggest that the region with mutation clustering is the major target ofCTL, and that the mutations evolve under the pressur