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 HB sAg‐positive patients (97 HB eAg‐positive and 280 HB eAg‐negative, genotypes A to E) who had liver biopsy were consecutively included. Host and viral factors ( ALT , HB sAg 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 HB eAg 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).