Predictors of treatment requirement in HBeAg-negative chronic hepatitis B patients with persistently normal alanine aminotransferase and high serum HBV DNA levels

摘要

Objectives: Serum alanine aminotransferase (ALT) is a controversial marker for disease monitoring in hepatitis B e antigen (HBeAg)-negative chronic hepatitis B (CHB) patients. The aim of this study was to determine the fibrosis stage and histological activity index (HAI) in HBeAg-negative CHB patients with persistently normal ALT (PNALT) and high serum HBV DNA (>=2000 IU/ml) and to investigate clinical risk factors for the requirement of treatment through the examination of liver biopsy specimens. Methods: HBeAg-negative CHB patients with PNALT (@?40 IU/l) and high serum HBV DNA (>=2000 IU/ml) were included. HBV fibrosis stage and HAI were scored according to the Ishak system. Multivariate logistic regression analysis was used to estimate the independent risk factors for fibrosis stage >=2 and/or HAI >=6. Receiver operating characteristic curve analysis was used to determine an optimal age cut-off for liver biopsy. Results: A total 120 patients were enrolled. These patients had a mean HBV DNA level of 123680+/-494500 IU/ml; the HBV DNA load was 2000-20000 IU/ml in 68 patients (56.6%) and >=20000 IU/ml in 52 (43.4%). Eighteen patients (15%) had moderate-to-severe histological activity (HAI >=6). Forty-three patients (35.9%) had a fibrosis stage >=2. Forty-eight patients (40%) had a fibrosis stage >=2 and/or HAI >=6. On multivariate logistic regression analysis, independent variables associated with fibrosis stage >=2 and/or HAI >=6 included age and HBV DNA viral load. Patients with HBV DNA 2000-20000 IU/ml were more likely to require treatment compared to those with a viral load >=20000 IU/ml. The optimal age cut-off to predict fibrosis stage >=2 and/or HAI >=6 was 46 years. Conclusions: Significant liver damage was detected in 40% of CHB patients with PNALT and high HBV DNA upon biopsy. Age and HBV DNA viral load were independent predictors of significant liver damage. A biopsy to determine the degree of liver damage is advisable for CHB patients older than 46 years.