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

摘要

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-naive 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).