乙肝e抗原阴性的乙肝慢性乙肝病毒感染者从童年预测到成年

StephenW

Viral Hepatitis
Predictors of hepatitis B e antigen-negative hepatitis in chronic hepatitis B virus-infected patients from childhood to adulthood

    Jia-Feng Wu1, Yu-Chun Chiu1,2, Kai-Chi Chang1,3, Huey-Ling Chen1,4, Yen-Hsuan Ni1,5, Hong-Yuan Hsu1 andMei-Hwei Chang1,4,*

Article first published online: 29 OCT 2015

DOI: 10.1002/hep.28222

© 2015 by the American Association for the Study of Liver Diseases

Issue
Hepatology

Volume 63, Issue 1, pages 74–82, January 2016
Article has an altmetric score of 2

Author Information

    1    Department of Pediatrics, National Taiwan University Children Hospital, National Taiwan University, Taipei, Taiwan
    2    Department of Medical Education, National Taiwan University Hospital, National Taiwan University, Taipei, Taiwan
    3    Department of Emergency, National Taiwan University Hospital, National Taiwan University, Taipei, Taiwan
    4    Hepatitis Research Center, National Taiwan University Hospital, National Taiwan University, Taipei, Taiwan
    5        Department of Genetics, National Taiwan University Hospital, National Taiwan University, Taipei, Taiwan

*Address reprint requests to: Mei-Hwei Chang, M.D., Department of Pediatrics, National Taiwan University Hospital, No. 8, Chung-Shan S. Rd., Taipei, Taiwan. E-mail: [email protected]; tel: +886-2-23123456, ext. 71723; fax: +886-2-23938871.

    Potential conflict of interest: Nothing to report.

    Supported by grants from the Ministry of Science and Technology of Taiwan (102-2314-B-002-039-MY2) and National Taiwan University Hospital (NTUH.104-S2663).

Hepatitis B e antigen (HBeAg)-negative hepatitis is a clinical indicator of poor outcome for chronic hepatitis B viral (HBV) infection. This long-term prospective cohort study aimed to elucidate the predictors of developing HBeAg-negative hepatitis in chronic HBV-infected subjects followed from childhood to adulthood. We followed 434 HBeAg-positive chronic HBV-infected patients from a median age of 7.22 years (interquartile range 4.31-10.21 years). Spontaneous HBeAg seroconversion occurred in 359 subjects at a median age of 13.93 years (interquartile range 8.76-20.59 years), and 75 subjects developed HBeAg seroconversion after antiviral therapy. These patients were followed for a median of 14.40 years (interquartile range 6.14-22.02 years) after HBeAg seroconversion. Clinical data were analyzed to delineate the predictors of developing HBeAg-negative hepatitis. The HBV basal core promoter and precore/core gene sequences were also evaluated in subjects with and without HBeAg-negative hepatitis. The overall annual incidence of HBeAg-negative hepatitis was 0.37% (95% confidence internal 0.35-0.39) in spontaneous HBeAg seroconverters. The overall annual incidence of HBeAg-negative hepatitis increased to 2.64% in lamivudine-treated subjects but did not increase in those treated with interferon-alpha (0.58%). Male gender (hazard ratio = 3.15), HBV genotype C (hazard ratio = 4.40), HBeAg seroconversion after 18 years of age (hazard ratio = 2.46), and lamivudine therapy prior to HBeAg seroconversion (hazard ratio = 1.42) were predictors of HBeAg-negative hepatitis in HBeAg seroconverters (P < 0.05). HBeAg-negative hepatitis subjects carried more A1762T/G1764A, C2063A, and A2131C HBV gene mutations than those without HBeAg-negative hepatitis. Conclusions: HBeAg seroconversion during childhood predicts a lower risk of HBeAg-negative hepatitis in later life. Interferon-alpha therapy may be an effective antiviral therapy beneficial in chronic HBV-infected children with severe inflammation that facilitates HBeAg seroconversion in earlier life. (Hepatology 2016;63:74–82)

StephenW

病毒性肝炎
乙肝e抗原阴性的乙肝慢性乙肝病毒感染者从童年预测到成年

    贾锋WU1，宇春Chiu1,2，凯驰Chang1,3，休伊灵Chen1,4，颜轩Ni1,5，宏远Hsu1 andMei-Hwei Chang1,4，*

文章首次在网上公布：2015年10月29日

DOI：10.1002 / hep.28222

©2015年肝病研究的美国协会

问题
肝病

卷63，第1期，页74-82，2016年一月
文章的altmetric比分2

作者信息

    儿科，台大儿童医院，国立台湾大学，台北，台湾1系
    医学教育，台大医院，国立台湾大学，台北，台湾的2部
    紧急情况下，台大医院，国立台湾大学，台北，台湾的3系
    4肝炎研究中心，台大医院，国立台湾大学，台北，台湾
    遗传学，台大医院，国立台湾大学，台北，台湾5系

*地址转载请：美Hwei张医师，儿科系，台大医院，8号仲山南路，台湾台北市。电子信箱：[email protected];联系电话：+ 886-2-23123456分机。 71723;传真：+ 886-2-23938871。

    潜在的利益冲突：无报告。

    从科学台湾（102-2314-B-002-039-MY2）和国立台湾大学医院（NTUH.104-S2663）和技术部资助。

乙肝e抗原（HBeAg）阴性肝炎的慢性乙型肝炎病毒（HBV）感染的预后不良临床指标。这种长期的前瞻性队列研究的目的是阐明制定的慢性HBV感染者HBeAg阴性乙肝的预测，随后从童年到成年。我们跟着434 HBeAg阳性慢性HBV感染者从7.22年（四分范围4.31​​-10.21岁），中位年龄。自发性HBeAg血清转换发生在359科目13.93岁（四分范围8.76-20.59岁），75受试者平均年龄发达HBeAg血清转换的抗病毒治疗后。随访14.40年（四分范围6.14-22.02岁）HBeAg血清转换后的中位数这些患者。临床资料进行分析，以划定发展HBeAg阴性乙肝的预测。乙肝基础核心启动子和前/核心基因序列进行了评价的科目和不HB​​eAg阴性乙肝。 HBeAg阴性乙肝的总体年发病率为0.37％（95％置信内部0.35-0.39）的自发性HBeAg血清转化。 HBeAg阴性乙肝的总体年发病率上升至2.64％，拉米夫定治疗的患者，但在那些与干扰素α（0.58％）处理后并没有增加。男性（危险比= 3.15），HBV C基因型之前，HBeAg血清学转换（危险比= 4.40），经过18年的年龄HBeAg血清学转换（危险比= 2.46），和拉米夫定治疗（风险比= 1.42）为HBeAg的预测在e抗原血清转化阴性肝炎（P <0.05）。 HBeAg阴性乙肝患者进行更A1762T / G1764A，C2063A和A2131C HBV基因突变比没有HBeAg阴性乙肝。结论：童年时HBeAg血清学转换的预测在以后的生活中HBeAg阴性乙肝的风险较低。 α-干扰素治​​疗可能是一种有效的抗病毒治疗有益的慢性HBV感染的儿童有严重的炎症，有利于HBeAg血清转换在早期生活。 （肝病2016年; 63：74-82）