前核心/核心启动子变异体预测显著纤维化两种HBeAg阳性和阴

StephenW

Precore/Core promoter variants to predict significant fibrosis in both HBeAg positive and negative chronic hepatitis B

    Martine Lapalus1, Cédric Laouenan2,3, Ana-Carolina Cardoso1, Emilie Estrabaud1, Roberto J. Carvalho-Filho1, Qian Zhang1, Olivier Lada1, Kevin Appourchaux1, Feryel Mouri4, Nathalie Boyer4, Pierre Bedossa5, Tarik Asselah1,4, Michelle Martinot-Peignoux1 andPatrick Marcellin1,4,*

Article first published online: 12 FEB 2015

DOI: 10.1111/liv.12787

© 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd

Issue

Liver International

Volume 35, Issue 9, pages 2082–2089, September 2015

    1    Team Physiopathology and Treatment of Viral Hepatitis, Centre de Recherche sur l'Inflammation, Laboratory of Excellence Labex INFLAMEX, INSERM, UMR-1149, University Denis Diderot Paris 7, PRES Sorbonne Paris Cité, Paris, France
    2    IAME, Inserm UMR-1137, University Denis Diderot Paris 7, Sorbonne Paris Cité, Paris, France
    3    Department of Biostatistics, Bichat Hospital, AP-HP, Paris, France
    4    Service d'Hépatologie, PMAD Hôpital Beaujon, AP-HP, Clichy, France
    5    Service d'Anatomie Pathologique, Hôpital Beaujon, Clichy, France

* Correspondence
Patrick Marcellin
Inserm UMR 1149 Centre Abrami, Hôpital Beaujon, 100 Blvd du Général Leclerc, Clichy 92110, France
Tel: +33 1 40 87 53 38
Fax: +33 1 47 30 94 40
e-mail: [email protected]

Keywords:

    basal core promoter variant;chronic hepatitis B;non-invasive marker;precore variant;significant fibrosis

Abstract
Background & Aims

Assessing fibrosis is essential in patients with chronic hepatitis B (CHB). The objective was to investigate the relationship between fibrosis, host and viral factors to identify non-invasive markers of significant fibrosis in a large cohort of unselected, well-characterized, treatment-naïve CHB patients.
Methods

Three hundred and seventy-seven HBsAg-positive patients (97 HBeAg-positive and 280 HBeAg-negative, genotypes A to E) who had liver biopsy were consecutively included. Host and viral factors (ALT, HBsAg and HBV-DNA levels, HBV genotype and precore (PC)/basal core promoter (BCP) variants) were determined on the day of the biopsy. Fibrosis stage was assessed using METAVIR score.
Results

Thirty-nine percent of the patients had significant fibrosis (METAVIR F ≥ 2). On univariate analysis, the stages of fibrosis F ≥ 2 were associated with older age (P < 0.0001), male gender (P = 0.01), higher ALT and HBV-DNA levels (P < 0.0001 and P = 0.0003, respectively), the presence of BCP (P < 0.0001) and BCP/PC variants (P < 0.0001). On multivariate analysis, age (P < 0.0001), the presence of HBV variants (P < 0.0001), HBV-DNA level (P = 0.0006) and ALT level (P = 0.02) were independently associated with significant fibrosis. The diagnostic accuracy of the combination (age, ALT, HBV-DNA, HBV variants) in predicting fibrosis F ≥ 2 was evidenced by a c-index of 0.76 (CI 95% 0.71–0.81).
Conclusions

We identified strong independent risk factors (age, ALT, HBV-DNA, HBV variants) predicting significant fibrosis (F ≥ 2) independently of HBeAg status in patients with CHB. Patients with BCP variants have a higher risk of severe liver disease. The detection of these mutants may help to predict significant fibrosis (F ≥ 2).

StephenW

前核心/核心启动子变异体预测显著纤维化两种HBeAg阳性和阴性慢性乙型肝炎

    马丁Lapalus1，塞德里克Laouenan2,3，安娜南卡罗来纳州Cardoso1，埃米莉Estrabaud1，罗伯特J.卡瓦略-Filho1，钱Zhang1，奥利维尔Lada1，凯文Appourchaux1，Feryel Mouri4，纳塔莉Boyer4，皮埃尔Bedossa5，塔里克Asselah1,4，米歇尔马丁诺特-Peignoux1 andPatrick Marcellin1,4，*

文章首次在线发表：2015年2月12日

DOI：10.1111 / liv.12787

2015年©约翰·威利父子A / S。由John Wiley＆Sons出版有限公司

问题

肝国际

第35卷，第9期，页2082年至2089年，2015年9月

    1队病理生理和法国治疗病毒性肝炎，中心德RECHERCHE河畔L'炎症，卓越Labex INFLAMEX实验室，INSERM的，UMR-1149，大学狄德罗巴黎7，PRES索邦太阳城巴黎，巴黎，
    2 IAME，INSERM UMR-1137，大学狄德罗7巴黎，巴黎的索邦大学太阳城，巴黎，法国
    生物统计学，比沙医院，AP-HP，巴黎，法国3系
    4服务D'Hépatologie，PMAD HOPITAL Beaujon，AP-HP，克利希，法国
    5 D'服务Pathologique Anatomie，HOPITAL Beaujon，克利希，法国

*通讯
帕特里克Marcellin
INSERM UMR 1149中心Abrami，HOPITAL Beaujon，100大道杜勒克莱尔将军，克利希92110，法国
联系电话：+33 1 40 87 53 38
传真：+33 1 47 30 94 40
电子邮件：[email protected]

关键词：

    基底核心启动子的变体;慢性乙型肝炎;非侵入性的标志;前C区变异;显著纤维化

抽象
背景与目的

评估纤维化是慢性乙型肝炎（CHB）是必不可少的。其目的是调查纤维化，主机和病毒因素，以确定选，良好的特点，治疗初治慢性乙肝患者的大型队列显著纤维化非创伤性指标之间的关系。
方法

三百七七HBsAg阳性的患者（97例HBeAg阳性和280例HBeAg阴性，基因型A到E）谁了肝活检连续列入。主机和病毒因素（ALT，HBsAg和HBV-DNA水平，HBV基因型和前C（PC）/基底核心启动子（BCP）的变种）是在活检当天决定。使用METAVIR评分纤维化阶段进行了评估。
结果

患者三十九％的有显著纤维化（METAVIR˚F≥2）。单变量分析显示，纤维化分期˚F≥2与年龄（P <0.0001），男性性别（P = 0.01），更高的ALT和HBV-DNA的水平（P <0.0001和P = 0.0003，分别）相关联，所述BCP的存在（P <0.0001）和BCP / PC变异（P <0.0001）。多变量分析显示，年龄（P <0.0001），对HBV变异的存在（P <0.0001），HBV-DNA水平（P = 0.0006）和ALT水平（P = 0.02）独立与显著纤维化。该组合的诊断准确性（年龄，ALT，HBV-DNA，HBV变体）在预测纤维化˚F≥2被证明一个0.76（95％CI 0.71-0.81）C指数。
结论

我们确定了强有力的独立危险因素（年龄，ALT，HBV-DNA，乙肝病毒变种）预测显著纤维化（F≥2）独立于HBeAg状态CHB患者。患者的BCP变体具有严重的肝脏疾病的风险较高。这些突变体的检测可能有助于预测显著纤维化（F≥2）。