Abstract: ObjectiveTo investigate the histological characteristics of hepatitis B e antigen (HBeAg)-negative chronic hepatitis B (CHB) patients with low viral load and to evaluate the diagnostic value of different criteria for inactive hepatitis B surface antigen (HBsAg) carriers (IC). Methods HBeAg-negative CHB patients with HBV DNA < 4.3 log₁₀ IU/mL and alanine aminotransferase (ALT) < 2 the upper limit of normal (ULN) were enrolled in the study. All patients underwent liver biopsy. Patients with histological activity index (HAI) ≤ 3 or mild liver pathological damage were defined as pathologically IC. Four clinical criteria were applied in the study. For diagnosis of IC, group A was based on the 2015 Chinese guidelines (normal ALT, HBV DNA < 2.3 log₁₀ IU/mL), group B was on the 2015 APASL or AASLD guidelines (normal ALT, HBV DNA < 3.3 log₁₀ IU/mL), group C was on ALT < 2 ULN and HBV DNA < 2.3 log₁₀ IU/mL, and Group D was on normal ALT and HBV DNA < 3.3 log₁₀ IU/mL. Diagnostic value of the 4 clinical criteria of IC was evaluated using liver biopsy, which was the golden standard. Results A total of 171 patients were enrolled, including 125 males and 46 females, with mean age of 45.5±4.24 (22-69) year old. HAI ranged from 1 to 11 with the average value of 4.3±2.1, which was ≤ 3 in 94 cases (55.0%). Fibrosis score ranged from 0 to 4 with the average value of 2.0±1.6. A total of 101 (59.1%) cases had fibrosis score from 0 to 1. There was no significant difference in IC diagnosis rate among the 4 groups with different clinical IC diagnostic criteria. The Yourdon′s index for the 4 criteria was 0.08 ~ 0.11 and the area under the curve (AUC) was 0.544 ~ 0.558, respectively, which suggested their limitation of IC diagnosis. There were only 50% ~ 60% patients pathologically diagnosed of IC in patients according to Chinese and APASL/AASLD guidelines. However, in the non-IC patients diagnosed with clinical criteria, there were 33.3% ~ 51.4% patients meeting the pathological IC diagnosis. Conclusion There were 50% ~ 60% patients meeting the pathological IC among HBeAg-negative CHB patients with low viral load. Among the non-IC patients diagnosed by clinical criteria, 33.3% ~ 51.4% patients were pathologically diagnosed of IC. Based on the diagnostic golden standard of histology, clinical diagnosis of IC with current Chinese, APASL and AASLD guidelines showed low sensitivity and limited value.

Key words: Chronic HBV infection, Inactive HBsAg carrying, Pathology, Diagnosis