LAUSR

BACKGROUND AND AIMS Immune tolerance is defined as HBeAg positive, high hepatitis B virus load (HBV), persistent normal alanine aminotransferase (ALT), no or slight inflammation or fibrosis in liver histology. However, it is still unclear the threshold of high hepatitis B virus load and how to predict histology without liver biopsy. The aim of this study was to predict immune tolerance in HBeAg positive, alanine aminotransferase -normal populations with non-invasive indicators. METHODS Two multi-center prospective cohort study recruited 907 treatment-naïve chronic hepatitis B (CHB) patients who had undergone liver biopsy in mainland China from August 2013 to September 2016 and April 2018 to June2019. Quantitative hepatitis B core antibody, AST and HBV DNA were investigated using commercial diagnostic assays and histological grading and staging was assessed by the Ishak scoring system. RESULTS One hundred and thirteen untreated CHB patients with HBeAg-positive, normal alanine aminotransferase (ALT) and high level of HBV DNA (≥5log10 IU/mL) were enrolled in this study. The area under the receiver operating characteristic curves (AUROCs) of qHBcAb, AST, HBV DNA and qHBcAb-AST index were 79.6%, 80.5%, 76.4% and 87.7%. Our novel qHBcAb-AST index, which combined qHBcAb and AST showed better performance with higher sensitivity (88.6% [95% confidence interval (CI) 72.3% - 96.3%]) and negative predictive value (NPV) (93.8% [95% CI 84.2% - 98.0%]). CONCLUSIONS The combination of qHBcAb and AST can more accurately predict the immune tolerance of people with HBeAg-positive, normal alanine aminotransferase (ALT).