Clinical noninvasive markers for antiviral therapy decision in chronic hepatitis B with alanine aminotransferase less than two times upper limit of normal

Summary Liver biopsy is the reference method for antiviral therapy decision‐making in chronic hepatitis B ( CHB ) when alanine aminotransferase ( ALT ) is less than two times of upper limit of normal (<2 ULN ). Our aim was to explore noninvasive markers for antiviral therapy decision in CHB with ALT  <2 ULN . A total of 452 treatment‐naïve CHB patients with ALT  < 2 ULN who had undergone liver biopsy were analysed in this prospective multi‐centre study. If liver biopsy showed moderate or severe inflammation (histology activity index ≥ 5) or significant fibrosis (Ishak fibrosis score ≥ 3), antiviral treatment was recommended. We analysed data using univariate and multivariate analyses and receiver operating characteristic curves ( ROC ). Two hundred and sixty‐nine (59.5%) of 452 cases with ALT  < 2 ULN had moderate, severe or significant inflammation. Aspartate aminotransferase ( AST ) ( P  = 0.03), anti‐hepatitis B virus core antibody (anti‐ HB c) ( P  = 0.003) and liver stiffness measurement ( LSM ) ( P  = 0.000) were independent variables for antiviral therapy decision‐making, with area under the ROC curve ( AUROC ) of 0.718, 0.703 and 0.819, respectively. Our novel AAF index, which combined AST , anti‐ HB c and LSM , showed better performance with AUROC of 0.876, 0.877 and 0.876 in estimation, validation and total set. Finally, 247 (54.6%) of 452 patients could avoid liver biopsy based on AAF index. Furthermore, performances of 23 noninvasive models were unsatisfactory for antiviral therapy decision with AUROC  < 0.800, which were inferior to AAF index. In conclusion, AST , anti‐ HB c and LSM were related to antiviral therapy decision‐making among CHB patients with ALT  < 2 ULN . Thus, the novel AAF index was a more reliable noninvasive model for antiviral therapy decision‐making.