较高比例的基础病毒核心启动子的突变会增加肝硬化的乙肝

StephenW

Gut 2015;64:292-302 doi:10.1136/gutjnl-2014-306977

    Hepatology

    Original article

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

    Tai-Chung Tseng1,2,
    Chun-Jen Liu3,4,
    Hung-Chih Yang3,5,
    Chi-Ling Chen4,
    Wan-Ting Yang6,7,
    Cheng-Shiue Tsai1,
    Stephanie Fang-Tzu Kuo8,
    Femke Carolien Verbree9,
    Tung-Hung Su3,4,
    Chia-Chi Wang1,
    Chen-Hua Liu3,4,
    Pei-Jer Chen3,4,
    Ding-Shinn Chen3,4,6,10,
    Jia-Horng Kao3,4,6,11

- Author Affiliations

    1Division of Gastroenterology, Department of Internal Medicine, Taipei Tzuchi Hospital, The Buddhist Tzuchi Medical Foundation, Taipei, Taiwan
    2School of Medicine, Tzu Chi University, Hualien, Taiwan
    3Division of Gastroenterology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
    4Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, Taipei, Taiwan
    5Department of Microbiology, National Taiwan University College of Medicine, Taipei, Taiwan
    6Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan
    7Master of Public Health Degree Program, National Taiwan University, Taipei, Taiwan
    8St Vincent's Hospital, Melbourne, Victoria, Australia
    9Medisch centrum haaglanden, The Hague, The Netherlands
    10Genomics Research Center, Academia Sinica, Taiwan
    11Department of Medical Research, National Taiwan University Hospital, Taipei, Taiwan

    Correspondence to Professor Jia-Horng Kao, Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, 1 Chang-Te St., Taipei 10002, Taiwan; [email protected]

    Received 12 February 2014
    Revised 22 March 2014
    Accepted 4 April 2014
    Published Online First 24 April 2014

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.

StephenW

肠道2015年;64：292-302 DOI：10.1136/ gutjnl-2014-306977

    肝病

    原创文章

较高比例的基础病毒核心启动子的突变会增加肝硬化的乙肝携带者的风险

    大涌Tseng1,2，
    骏仁Liu3,4，
    洪智Yang3,5，
    林志玲Chen4，
    万婷Yang6,7，
    成Shiue Tsai1，
    斯蒂芬妮芳姿Kuo8，
    Femke Carolien Verbree9，
    东红Su3,4，
    林嘉绮旺1，
    陈桦Liu3,4，
    裴哲Chen3,4，
    鼎希恩Chen3,4,6,10，
    佳鸿Kao3,4,6,11

- 作者所属机构

    消化内科，内科，台北Tzuchi医院，佛教Tzuchi医学基金会，台北，台湾1区
    医药，慈济大学，花莲，台2School
    消化内科，内科，台大医院系，台北，台湾3Division
    临床医学研究所4Graduate，医学国立台湾大学，台北，台湾
    微生物学，医学国立台湾大学，台北，台湾5Department
    6Hepatitis研究中心，台大医院，台北，台湾
    公共卫生学位课程，国立台湾大学，台北，台湾7Master
    56.2文森特医院，墨尔本，维多利亚，澳大利亚
    9Medisch椎体haaglanden，海牙，荷兰
    10Genomics研究中心，台湾中央研究院
    医学研究，台大医院，台北，台湾11Department

    对应教授贾泓花王，临床医学研究所，医学国立台湾大学，1昌特街，台北10002，台湾; [email protected]

    收到2014年2月12日
    修订后的2014年3月22日
    接受2014年4月4日
    网上公布的第一2014年4月24日

抽象

背景与目的前C（PC）的变体（G1896A）和基础核心启动子（BCP）变异的乙肝病毒（A1762T/ G1764A）与肝癌的乙肝病毒携带者风险。然而，鲜为人知的是，他们对乙肝e抗原（HBeAg）阴性肝炎和肝硬化的不利结果的影响。

方法：251自发性HBeAg血清转化谁了B型或C感染，并获得了长期的随访患者。 PC和BCP突变体确定定性和定量关联与这些不良后果。调查结果由独立的病例对照研究，其中包括184例活检证实为肝纤维化分期进行了验证。

结果在纵向队列研究，BCP突变，可能PC野生型肝硬化的发展有关联，但不是HBeAg阴性乙肝。多变量分析显示，只有BCP突变是肝硬化发展的一个独立的危险因素。使用BCP突变体的定量分析，较高比例的BCP突变体的，其定义为一个连续的变量，一个二分变量或序数的变量，被与肝硬化的风险较高。如果我们选择BCP突变为截止的45％，肝硬化的风险的患者的BCP突变≥45％相比，在纵向队列<45％以上;这一发现被证实的病例对照研究（调整OR：2.81，95％CI1.40至5.67）。

结论BCP突变的比例较高增加肝硬化发展的乙肝病毒携带者与B型或C感染的危险。