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Higher proportion of viral basal core promoter mutant increases the risk of liver cirrhosis in hepatitis B carriers
  1. Tai-Chung Tseng1,2,
  2. Chun-Jen Liu3,4,
  3. Hung-Chih Yang3,5,
  4. Chi-Ling Chen4,
  5. Wan-Ting Yang6,7,
  6. Cheng-Shiue Tsai1,
  7. Stephanie Fang-Tzu Kuo8,
  8. Femke Carolien Verbree9,
  9. Tung-Hung Su3,4,
  10. Chia-Chi Wang1,
  11. Chen-Hua Liu3,4,
  12. Pei-Jer Chen3,4,
  13. Ding-Shinn Chen3,4,6,10,
  14. Jia-Horng Kao3,4,6,11
  1. 1Division of Gastroenterology, Department of Internal Medicine, Taipei Tzuchi Hospital, The Buddhist Tzuchi Medical Foundation, Taipei, Taiwan
  2. 2School of Medicine, Tzu Chi University, Hualien, Taiwan
  3. 3Division of Gastroenterology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
  4. 4Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, Taipei, Taiwan
  5. 5Department of Microbiology, National Taiwan University College of Medicine, Taipei, Taiwan
  6. 6Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan
  7. 7Master of Public Health Degree Program, National Taiwan University, Taipei, Taiwan
  8. 8St Vincent's Hospital, Melbourne, Victoria, Australia
  9. 9Medisch centrum haaglanden, The Hague, The Netherlands
  10. 10Genomics Research Center, Academia Sinica, Taiwan
  11. 11Department of Medical Research, National Taiwan University Hospital, Taipei, Taiwan
  1. Correspondence to Professor Jia-Horng Kao, Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, 1 Chang-Te St., Taipei 10002, Taiwan; kaojh{at}ntu.edu.tw

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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