Higher proportion of viral basal core promoter mutant increases the risk of liver cirrhosis in hepatitis B carriers
Journal
Gut
Journal Volume
64
Journal Issue
2
Pages
292-302
Date Issued
2015
Author(s)
Yang W.-T
Tsai C.-S
Kuo S.F.-T
Verbree F.C
Wang C.-C
Abstract
Background and objective: Precore (PC) variant (G1896A) and basal core promoter (BCP) variant (A1762T/G1764A) of HBV are associated with risk of hepatocellular carcinoma in HBV carriers. However, little is known about their impact on the adverse outcomes of hepatitis B e antigen (HBeAg)-negative hepatitis and liver cirrhosis. Methods: 251 spontaneous HBeAg seroconverters who had genotype B or C infection and received a long-term follow-up were enrolled. PC and BCP mutants were determined qualitatively and quantitatively to correlate with these adverse outcomes. The findings were validated by an independent case -control study, which included 184 patients with biopsy-proven liver fibrosis stages. Results: In the longitudinal cohort study, BCP mutant and possibly PC wild type were associated with cirrhosis development, but not HBeAg-negative hepatitis. Multivariable analysis showed that only BCP mutant was an independent risk factor for cirrhosis development. Using quantitative analysis of BCP mutant, a higher proportion of BCP mutant, defined as a continuous variable, a dichotomous variable or an ordinal variable, was associated with a higher risk of cirrhosis. If we chose 45% of BCP mutant as the cut-off, the risk of cirrhosis was higher in patients with BCP mutant ? 45% compared to <45% in the longitudinal cohort; this finding was validated by the case -control study (adjusted OR: 2.81, 95% CI 1.40 to 5.67). Conclusions: A higher proportion of BCP mutant increases the risk of liver cirrhosis development in HBV carriers with genotype B or C infection.
SDGs
Other Subjects
adult; adverse outcome; Article; case control study; cohort analysis; controlled study; disease association; female; hepatitis B; Hepatitis B virus; human; liver cirrhosis; longitudinal study; major clinical study; male; promoter region; qualitative analysis; quantitative analysis; risk factor; viral genetics; virus core; virus mutant; blood; classification; complication; genetics; hepatitis B; heterozygote; immunology; isolation and purification; liver cirrhosis; middle aged; mutation; virology; hepatitis B core antigen; virus DNA; Adult; Carrier State; Case-Control Studies; DNA, Viral; Female; Hepatitis B; Hepatitis B Core Antigens; Hepatitis B virus; Humans; Liver Cirrhosis; Longitudinal Studies; Male; Middle Aged; Mutation; Promoter Regions, Genetic; Risk Factors
Publisher
BMJ Publishing Group
Type
journal article