AIM: To determine whether new cut-off values for alanine aminotransferase (ALT) and baseline hepatitis B virus (HBV) DNA levels better differentiate HBeAg(-) chronic hepatitis B (CHB) patients from inactive chronic carriers. METHODS: Ninety-one patients [32 HBeAg(+) CHB, 19 inactive carriers and 40 HBeAg(-) CHB] were followed up for 2 years and were tested for HBV DNA levels by a PCR-based assay. ALT was tested twice during the last 6 mo using new cut-off values: ULN (upper limit of normal) 30 IU/L for males, 19 IU/L for females. Diagnostic accuracy, sensitivity, specificity, positive and negative predictive values were calculated by discriminant analysis. RESULTS: When using the revised ALT cut-off values, the lowest optimal HBV DNA level that differentiated HBeAg(-) CHB patients from inactive carriers was 50 000 copies/mL. The diagnostic accuracy of HBV DNA to determine inactive carriers with a cut-off of 50 000 copies/mL was similar to the previously recommended cut-off of 100 000 copies/mL (91%). HBV DNA levels were lower than the cut-off value in 95% of inactive carriers and in 28% of HBeAg(-) CHB patients. With ALT 30 IU in men and > 19 IU in women and baseline HBV DNA levels were > 100 000 copies/mL, the risk is 86%. CONCLUSION: New cut-off values for ALT together with HBV DNA levels proposed by AASLD (American Association for the Study of Liver Diseases) and NIH (National Institute of Health) consensus seem appropriate to characterize inactive carriers.