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). 作者: StephenW 时间: 2015-2-1 10:55