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]
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).