Predictive Value of Hepatitis B Surface Antigen and Gamma-Glutamyl Transpeptidase for Significant Liver Fibrosis Among Patients with Immune-Tolerant Phase Chronic Hepatitis B

Background: Hepatitis B e antigen (HBeAg)-positive chronic hepatitis B (CHB) in the immune-tolerant (IT) phase is significantly associated with high risk for hepatocellular carcinoma (HCC), suggesting requirement for antiviral therapy particularly for those with histological liver injury. This study aimed to develop a noninvasive model to predict significant liver fibrosis among IT-phase CHB patients. Methods: 113 IT-phase CHB patients were retrospectively recruited and divided into two histopathological groups according to their histological profiles: necroinflammatory score <4 (N<4)/fibrosis score ≥1 (F0-1), and necroinflammatory score ≥4 (N≥4)/ fibrosis score ≥2 (F2-4). Multivariate analysis was conducted to assess the predictive value of the noninvasive model for significant liver fibrosis. Findings: IT-phase CHB patients with N<4/F0-1 had significantly higher HBsAg levels than those with N≥4/F2-4. The optimal HBsAg level of log 4.44 IU/mL for significant liver fibrosis (F≥2) gave an AUC of 0.83, sensitivity of 81.1%, specificity of 81.6%, positive predictive value (PPV) of 68.2%, and negative predictive value (NPV) of 89.9%. An IT-model with HBsAg and GGT in combination was established, and it had an AUC of 0.86, sensitivity of 86.5%, specificity of 81.6%, PPV of 69.6, NPV of 92.5, and accuracy (AC) of 83.2% to predict F≥2 in the IT-phase CHB patients. Notably, the IT-model exhibited higher predictive value than the existing aspartate aminotransferase-to-platelet ratio index, Fibrosis-4 score, and GGT to platelet ratio. Interpretation: The established IT-model combing HBsAg and GGT has good performance in predicting significant liver fibrosis in IT-phase CHB patients.   Funding: This study was supported by the Science and Technology Department of Fujian [2018J01164], and Professor Academic Development Fund of Fujian Medical University [2015j01460]. Declaration of Interest: All authors declare no conflict of interest. Ethical Approval: The study protocol was reviewed and approved by the Institutional Review Board (IRB) of the First Affiliated Hospital of Fujian Medical University, and the need for informed consent from each patient was waived due to its retrospective nature.