VARIATIONS OF HEPATITIS-B VIRUS CORE GENE SEQUENCE IN WESTERN PATIENTS WITH CHRONIC HEPATITIS-B VIRUS-INFECTION

Heterogeneity of the hepatitis B virus (HBV) core gene has been report ed to be associated with the presence of active liver disease in Japan ese patients with chronic HBV infection, This study evaluated the sign ificance of HBV core gene heterogeneity in Western patients with chron ic HBV infection, The hepatitis B virus precore/core gene from 45 pati ents (inactive:active liver disease ratio 16:29) was amplified from se rum by polymerase chain reaction (PCR), Gel electrophoresis was employ ed to detect large deletions, The PCR amplicons from 13 patients (all HBV serotype adw but with a different spectrum of liver disease) were cloned and sequenced, Hepatitis B surface antigen (HBsAg) serotypes we re tested by enzyme immuno-assay (EIA) and hepatic expression of HBV a ntigens was assessed by immunohistochemistry. The HBV core gene was am plified from the serum of all 45 patients. Three patients had mixed in fection with both precore mutant and wild-type HBV and all three had a ctive liver disease, No patient had a large deletion of the HBV core g ene. Hepatitis B virus core gene sequence variations were more common in the midcore region and there was no difference in the number of sil ent and missense substitutions between those with inactive and active liver disease. There was no correlation between the nucleotide or enco ded amino acid substitutions and the clinical and biochemical paramete rs, including the subsequent response to interferon-alpha therapy (n = 37) or hepatic HBV antigen expression, Variation of the HBV core gene was not found to be preferentially associated with active liver disea se in Western patients with chronic HBV infection, The pattern of hepa titis B core gene variation is in accord with the genomic organization of HBV.