A 13-year longitudinal study of the impact of double mutations in the core promoter region of hepatitis B virus on HBeAg seroconversion and disease progression in patients with genotype C chronic active hepatitis

• Published in: Journal of viral hepatitis Vol. 14; no. 3; pp. 169 - 175
• Main Authors: Jang, J. W., Lee, Y. C., Kim, M. S., Lee, S. Y., Bae, S. H., Choi, J. Y., Yoon, S. K.
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01.03.2007
• Subjects: Adolescent; Adult; basic core promoter; Carcinoma, Hepatocellular - virology; Carrier State - virology; chronic hepatitis B; Disease Progression; Female; Genotype; Hepatitis B Antibodies - blood; hepatitis B e antigen; Hepatitis B e Antigens - blood; Hepatitis B e Antigens - immunology; Hepatitis B virus; Hepatitis B virus - genetics; Hepatitis, Chronic - complications; Hepatitis, Chronic - immunology; Hepatitis, Chronic - pathology; Hepatitis, Chronic - virology; Humans; Liver - pathology; Liver Cirrhosis - virology; Liver Function Tests; Longitudinal Studies; Male; Middle Aged; Mutation; Promoter Regions, Genetic; seroconversion
• ISSN: 1352-0504; 1365-2893
• DOI: 10.1111/j.1365-2893.2006.00788.x

The pathogenic role of core promoter (CP) mutations (T1762/A1764) of hepatitis B virus (HBV) in hepatitis B e antigen (HBeAg) seroconversion or disease progression remains unclear. We investigated the clinical relevance of these mutants over a long‐term follow‐up period of up to 15 years. In this longitudinal cohort study, 29 HBeAg‐positive patients with biopsy‐proved chronic active hepatitis without cirrhosis were regularly monitored for >10 years. The viral isolates were characterized, using the frozen liver tissue obtained on the day of biopsy. Long‐term outcomes were compared between patients with and without CP mutations of HBV at baseline. HBV genotyping showed that 100% of study subjects were infected with genotype C HBV. During a median follow‐up period of 12.5 years, patients without double CP mutations of HBV at baseline showed a tendency towards achieving an earlier HBeAg seroconversion than those with (6.9 vs 9.4 years, P = 0.062) double CP mutations. Double CP mutations at baseline were also significantly associated with the eventual development of cirrhosis or hepatocellular carcinoma (P = 0.013), whereas the absence of double CP mutations predicted inactive carrier status at the last follow‐up (P = 0.027). At 10 years, liver‐related tests were also significantly better in patients without double CP mutations of HBV than in those with these mutations, as reflected by higher platelet counts and albumin levels (P = 0.036 and P = 0.044, respectively). Double T1762/A1764 mutations are significantly related to liver deterioration in HBeAg‐positive genotype C active hepatitis patients. A longer period of immune clearance coupled with delayed HBeAg seroconversion appears to contribute to disease progression in patients harbouring these mutations in the CP region of HBV.