Mutations of precore and proximal core regions of hepatitis B virus genomein serum of hepatocellular carcinoma patients

In the present study, genetic alterations of the precore and proximal core regions (codons 1-50) were determined in HBV isolated from the serum of 58 patients with HCC and hepatitis B surface antigen (HBsAg) in their serum to identify any role of such genetic changes in HBV genome for hepatocarcinog enesis. DNA extracted from the serum of 16 patients with chronic hepatitis B but no HCC were used as controls. In HCC patients, mutations of T-1846, C -1858, A(1896), and A(1899) were identified in 48, 5, 86 and 36%, respectiv ely. A(1896) mutation is associated with T-1846 and A(1899) mutations more frequently in HCC patients than in chronic hepatitis B patients. Fourteen m utations of the proximal core region in HBV genomes from HCC patients were observed in codons 5, 13, 21, 22, 26, 27, 31, 35 and 41. The median number of mutations in the proximal core gene was 7 from HBeAg-negative HCCs, 5 in HBeAg-positive HCCs, and 4 in patients with chronic hepatitis B without HC C. These results suggest that mutations of the precore and proximal core ge ne sequences may preferentially occur in specific nucleotides and the conti nuous replication of such mutant HBV might play a role in HBV-related hepat ocarcinogenesis. (C) 1999 Elsevier Science Ltd. All rights reserved.