Tai-Chung Tseng1, Chun-Jen Liu2, Hung-Chih Yang3, Chi-Ling Chen4, Wan-Ting Yang5, Cheng-Shiue Tsai6, Stephanie Fang-Tzu Kuo7, Femke Carolien Verbree8, Tung-Hung Su2, Chia-Chi Wang6, Chen-Hua Liu2, Pei-Jer Chen2, Ding-Shinn Chen9, Jia-Horng Kao10. 1. Division of Gastroenterology, Department of Internal Medicine, Taipei Tzuchi Hospital, The Buddhist Tzuchi Medical Foundation, Taipei, Taiwan School of Medicine, Tzu Chi University, Hualien, Taiwan. 2. Division of Gastroenterology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, Taipei, Taiwan. 3. Division of Gastroenterology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan Department of Microbiology, National Taiwan University College of Medicine, Taipei, Taiwan. 4. Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, Taipei, Taiwan. 5. Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan Master of Public Health Degree Program, National Taiwan University, Taipei, Taiwan. 6. Division of Gastroenterology, Department of Internal Medicine, Taipei Tzuchi Hospital, The Buddhist Tzuchi Medical Foundation, Taipei, Taiwan. 7. St Vincent's Hospital, Melbourne, Victoria, Australia. 8. Medisch centrum haaglanden, The Hague, The Netherlands. 9. Division of Gastroenterology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, Taipei, Taiwan Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan Genomics Research Center, Academia Sinica, Taiwan. 10. Division of Gastroenterology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, Taipei, Taiwan Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan Department of Medical Research, National Taiwan University Hospital, Taipei, Taiwan.
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. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.
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. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.
Authors: Eleanor A Powell; Ceejay L Boyce; Maemu P Gededzha; Selokela G Selabe; M Jeffrey Mphahlele; Jason T Blackard Journal: J Gen Virol Date: 2016-03-31 Impact factor: 3.891