前C/核心启动子变异体预测显著纤维化两种HBeAg阳性和阴性慢

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 Ferreira Netto Cardoso1,
    Emilie Estrabaud1,
    Roberto Carvalho-Filho1,
    Qian Zhang1,
    Olivier Lada1,
    Kevin Appourchaux1,
    Feryel Mouri4,
    Nathalie Boyer4,
    Pierre Bedossa5,
    Tarik Asselah1,2,3,4,
    Michelle Martinot-Peignoux1 and
    Patrick Marcellin1,2,3,4,*

DOI: 10.1111/liv.12787

This article is protected by copyright. All rights reserved.

Issue
Cover image for Vol. 35 Issue 2
Liver International

    1    INSERM, UMR1149, Team Physiopathology and Treatment of Viral Hepatitis, Centre de Recherche sur l'Inflammation, University Denis Diderot Paris 7, Paris, France
    2    IAME, Inserm UMR-1137, Univ Paris Diderot, 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

* Corresponding author:
Patrick Marcellin
Inserm UMR 1149 Centre Abrami
Hôpital Beaujon
100 Blvd du Général Leclerc
92110 CLICHY
France
Tel 33 1 40 87 53 38
Fax 33 1 47 30 94 40
E-mail: [email protected]

    This article has been accepted for publication and undergone full peer review but has not been through the copyediting, typesetting, pagination and proofreading process, which may lead to differences between this version and the Version of Record. Please cite this article as doi: 10.1111/liv.12787




Abstract
Background and 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

38% 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<.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

吨
前C/核心启动子变异体预测显著纤维化两种HBeAg阳性和阴性慢性乙肝

    马丁Lapalus1，
    塞德里克Laouenan2,3，
    安娜·费雷拉北卡罗来纳州内托Cardoso1，
    埃米莉Estrabaud1，
    罗伯托·卡瓦略，Filho1，
    钱Zhang1，
    奥利维尔Lada1，
    凯文Appourchaux1，
    Feryel Mouri4，
    娜塔莉Boyer4，
    皮埃尔Bedossa5，
    塔里克Asselah1,2,3,4，
    米歇尔·马丁诺德-Peignoux1和
    帕特里克Marcellin1,2,3,4，*

DOI：10.1111/ liv.12787

这篇文章是受版权保护的。版权所有。

问题
封面图片的卷。 35第2期
肝国际

    1 INSERM，UMR1149，团队病理生理学病毒性肝炎，中心德RECHERCHE河畔L'炎症，大学狄德罗巴黎7和处理，巴黎，法国
    2 IAME，INSERM UMR-1137，巴黎大学狄德罗，法国巴黎
    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服务D'Anatomie Pathologique，HOPITAL Beaujon，克利希，法国

*通讯作者：
帕特里克Marcellin
INSERM UMR1149中心Abrami
HOPITAL Beaujon
100大道杜总勒克莱尔
92110 CLICHY
法国
电话33140875338
传真33147309440
电子邮件：[email protected]

    这篇文章已被接受发表，并接受全面的同行评审，但经过审稿，排版，分页和校对过程中，这可能会导致这个版本和记录的版本之间的差异一直没有。请引用这篇文章的DOI：10.1111/ liv.12787




抽象
背景和目的

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无创标记之间的关系。
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）谁了肝活检被连续列入。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评分纤维化分期进行了评估。
结果

患者38％有显著纤维化（METAVIRF≥2）。单变量分析显示，纤维化F≥2的阶段与年龄（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，分别地），所述有关联存在BCP（P <0.0001）和BCP/ PC变异（P <0.0001）。多变量分析显示，年龄（P <0.0001），乙肝病毒变异的存在（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。相结合的诊断准确率（年龄，ALT，HBV-DNA，乙肝病毒变种）在预测纤维化F≥2被证明的0.76 C指数[95％CI0.71-0.81]。
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）