Hepatitis B virus infection leads to a wide spectrum of liver injury,
including self-limited acute hepatitis, fulminant hepatitis and chroni
c hepatitis with progression to cirrhosis or acute exacerbation to liv
er failure, as well as an asymptomatic chronic carrier state. The hepa
titis B core antigen could be an immunological target of cytotoxic T l
ymphocytes. To investigate the reason why the severe immunological att
ack occurs, the entire precore and core region was sequenced. No signi
ficant change in deduced amino acid residue was noted in all the asymp
tomatic healthy carriers and all the self-limited acute hepatitis pati
ents. In contrast, clustering changes in small segments of amino acids
were found in all the patients with severe chronic liver disease and
in all the fatal hepatitis cases. These data suggest that these region
s with mutations may play an important role in the pathogenesis of hep
atitis B viral disease, and such mutations are related to severe liver
damage.