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

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).

• Authors: Martine Lapalus, Cédric Laouenan, Ana-Carolina Cardoso, Emilie Estrabaud, Roberto J Carvalho-Filho, Qian Zhang, Olivier Lada, Kevin Appourchaux, Feryel Mouri, Nathalie Boyer, Pierre Bedossa, Tarik Asselah, Michelle Martinot-Peignoux, Patrick Marcellin
• Journal: Liver international : official journal of the International Association for the Study of the Liver (Liver Int) Vol. 35 Issue 9 Pg. 2082-9 (Sep 2015) ISSN: 1478-3231 [Electronic] United States
• PMID: 25612083 (Publication Type: Journal Article)
• Copyright: © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Chemical References

• Biomarkers
• DNA, Viral
• Hepatitis B Surface Antigens
• Hepatitis B e Antigens

Topics

• Adult
• Biomarkers
• DNA, Viral (blood)
• Female
• Fibrosis
• Genotype
• Hepatitis B Surface Antigens (blood)
• Hepatitis B e Antigens (blood)
• Hepatitis B virus (genetics)
• Hepatitis B, Chronic (complications)
• Humans
• Liver (pathology)
• Male
• Middle Aged
• Multivariate Analysis
• Mutation
• Prognosis
• Promoter Regions, Genetic
• Risk Factors
• Young Adult