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- Title
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.
- Authors
Jang, J. W.; Lee, Y. C.; Kim, M. S.; Lee, S. Y.; Bae, S. H.; Choi, J. Y.; Yoon, S. K.
- Abstract
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.
- Subjects
HEPATITIS B virus; CHRONIC active hepatitis; LIVER cancer; VIRAL hepatitis; COHORT analysis; GENETIC research
- Publication
Journal of Viral Hepatitis, 2007, Vol 14, Issue 3, p169
- ISSN
1352-0504
- Publication type
Article
- DOI
10.1111/j.1365-2893.2006.00788.x