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

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 (<2ULN). Our aim was to explore noninvasive markers for antiviral therapy decision in CHB with ALT <2ULN. A total of 452 treatment-naïve CHB patients with ALT < 2ULN 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 < 2ULN had moderate, severe or significant inflammation. Aspartate aminotransferase (AST) (P = 0.03), anti-hepatitis B virus core antibody (anti-HBc) (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-HBc 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-HBc and LSM were related to antiviral therapy decision-making among CHB patients with ALT < 2ULN. Thus, the novel AAF index was a more reliable noninvasive model for antiviral therapy decision-making.