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

•Serum alanine aminotransferase (ALT) is a controversial marker for monitoring disease in hepatitis B e antigen (HBeAg)-negative chronic hepatitis B (CHB) patients.•A significant proportion of HBeAg-negative hepatitis B virus (HBV)-infected patients with high HBV DNA levels may have significant histological liver abnormalities despite persistently normal ALT.•Age and HBV DNA viral load were independent predictors of significant liver damage in HBeAg-negative CHB patients with persistently normal ALT.

SummaryObjectivesSerum 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.MethodsHBeAg-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.ResultsA total 120 patients were enrolled. These patients had a mean HBV DNA level of 123 680 ± 494 500 IU/ml; the HBV DNA load was 2000-20 000 IU/ml in 68 patients (56.6%) and ≥20 000 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 2000-20 000 IU/ml were more likely to require treatment compared to those with a viral load ≥20 000 IU/ml. The optimal age cut-off to predict fibrosis stage ≥2 and/or HAI ≥6 was 46 years.ConclusionsSignificant 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.