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. 2015 Feb;64(2):292-302.
doi: 10.1136/gutjnl-2014-306977. Epub 2014 Apr 24.

Higher proportion of viral basal core promoter mutant increases the risk of liver cirrhosis in hepatitis B carriers

Tai-Chung Tseng  1 , Chun-Jen Liu  2 , Hung-Chih Yang  3 , Chi-Ling Chen  4 , Wan-Ting Yang  5 , Cheng-Shiue Tsai  6 , Stephanie Fang-Tzu Kuo  7 , Femke Carolien Verbree  8 , Tung-Hung Su  2 , Chia-Chi Wang  6 , Chen-Hua Liu  2 , Pei-Jer Chen  2 , Ding-Shinn Chen  9 , Jia-Horng Kao  10
Affiliations

Higher proportion of viral basal core promoter mutant increases the risk of liver cirrhosis in hepatitis B carriers

Tai-Chung Tseng et al. Gut. 2015 Feb.

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.

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