Liver Inflammation and Fibrosis of HBeAg-Negative Patients in the Grey Zone

Background: Few studies have reported the disease severity of HBeAg negative patients with chronic hepatitis B (CHB) in the grey zone (GZ). This study aimed to investigate the degree of liver injury in the HBeAg negative GZ patients. Methods: One hundred and thirty-two treatment-naïve HBeAg negative GZ patients with HBV DNA ≥ 2,000 IU/ml and ALT < 80 U/L who underwent liver biopsy were included. Liver histology was evaluated using the Scheuer classification system. Logistic regression analysis was used to identify independent risk factors of significant liver inflammation and fibrosis. Results: The median age of patients was 43.0 years and the median levels of HBV DNA was 4.3 log 10 IU/mL. The majority of patients (65.2%) were male. The distributions of liver fibrosis stages of patients were as follows: S0, 7 (5.3%); S1, 44 (33.3%); S2, 32 (24.2%); S3, 20 (15.2%); and S4, 29 (22.0%). The distributions of liver inflammation grades were: G0, 0 (0%); G1, 40 (30.3%); G2, 65 (49.2%); G3, 32 (24.2%); and G4, 20 (15.2%). The serum AST (1.051, 95%CI 1.008-1.096, P=0.019) and HBV DNA (1.579, 95%CI 1.023-2.438, P=0.039) levels were independently risk factors of significant liver fibrosis. The serum AST (1.072, 95%CI 1.023-1.124, P=0.004) was the only independently risk factor of significant liver inflammation. Serum HBV DNA and AST had moderate accuracy of predicting significant liver fibrosis and inflammation. Conclusion: Substantial patients exhibited significant liver injury in HBeAg negative GZ patients. High HBV DNA and AST levels were two independent risk factors of significant liver injury.