Accepted Article
Received Date : 31-Oct-2014 Revised Date : 19-Dec-2014 Accepted Date : 15-Jan-2015 Article type : Original Articles
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 Asselah1-4, Michelle MartinotPeignoux1, Patrick Marcellin1-4
1. INSERM, UMR1149, Team Physiopathology and Treatment of Viral Hepatitis, Centre de Recherche sur l’Inflammation; University Denis Diderot Paris 7, site Bichat, BP 416, Laboratory of Excellence Labex INFLAMEX, PRES Sorbonne Paris Cité, Paris, France 2. IAME, Inserm UMR-1137, Univ Paris Diderot, 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
Corresponding author: Patrick Marcellin Inserm UMR 1149 Centre Abrami Hôpital Beaujon 100 Blvd du Général Leclerc 92110 CLICHY France 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 This article is protected by copyright. All rights reserved.
Accepted Article
Tel 33 1 40 87 53 38 Fax 33 1 47 30 94 40 E-mail: [email protected]
Abbreviations: CHB, chronic hepatitis B; HCC, hepatocellular carcinoma; HBsAg, hepatitis B surface antigen; HBeAg, hepatitis B e antigen; PC, precore; BCP, basal core promoter; IFNL3, interferon lambda 3; HCV, hepatitis C virus; ALT, alanine aminotransferase; WT, wild-type; PCR, polymerase chain reaction; SD, standard deviation; CI, confidence interval; PPV, positive predictive value; NPV, negative predictive value; BMI, body mass index; ULN, upper limit of normal; OR, odds ratio.
Conflict of interest: The authors have nothing to disclose.
Financial support: None
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
Received Date : 31-Oct-2014 Revised Date : 19-Dec-2014 Accepted Date : 15-Jan-2015 Article type : Original Articles
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 Asselah1-4, Michelle MartinotPeignoux1, Patrick Marcellin1-4
1. INSERM, UMR1149, Team Physiopathology and Treatment of Viral Hepatitis, Centre de Recherche sur l’Inflammation; University Denis Diderot Paris 7, site Bichat, BP 416, Laboratory of Excellence Labex INFLAMEX, PRES Sorbonne Paris Cité, Paris, France 2. IAME, Inserm UMR-1137, Univ Paris Diderot, 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
Corresponding author: Patrick Marcellin Inserm UMR 1149 Centre Abrami Hôpital Beaujon 100 Blvd du Général Leclerc 92110 CLICHY France 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 This article is protected by copyright. All rights reserved.
Accepted Article
Tel 33 1 40 87 53 38 Fax 33 1 47 30 94 40 E-mail: [email protected]
Abbreviations: CHB, chronic hepatitis B; HCC, hepatocellular carcinoma; HBsAg, hepatitis B surface antigen; HBeAg, hepatitis B e antigen; PC, precore; BCP, basal core promoter; IFNL3, interferon lambda 3; HCV, hepatitis C virus; ALT, alanine aminotransferase; WT, wild-type; PCR, polymerase chain reaction; SD, standard deviation; CI, confidence interval; PPV, positive predictive value; NPV, negative predictive value; BMI, body mass index; ULN, upper limit of normal; OR, odds ratio.
Conflict of interest: The authors have nothing to disclose.
Financial support: None
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
