Alanine aminotransferase course, serum hepatitis B virus DNA, and liver stiffness measurement for therapeutic decisions in hepatitis B e antigen-negative chronic hepatitis B.

Aim: To evaluate the utility of the combination of alanine aminotransferase (ALT) course, hepatitis B virus (HBV) DNA level, and liver stiffness measurement (LSM) for determining significant liver disease in hepatitis B e antigen (HBeAg)-negative patients. Methods: Three hundred and ninety nine consecutive HBeAg-negative patients with HBV DNA > 2000 IU/mL and documented serial measurements of ALT were enrolled to undergo LSM followed by liver biopsy. Results: Using ALT < 40 IU/L as a normal value, 142 patients had persistently normal ALT (PNALT), whereas 257 had persistently or intermittently elevated ALT (PIEALT) in the prior year. Among patients with HBV DNA of 2000-19 999, 20 000199 999, and >= 200 000 IU/mL, significant pathological lesions defined as the presence of moderate to severe necroinflannrnation and/or significant fibrosis by METAVIR scoring was present in 40%, 45%, and 71% of the PIEALT group, and 15%, 31%, and 36% of the PNALT group, respectively. In PNALT patients with HBV DNA < 20 000 IU/mL, liver biopsy could be avoided in 88% when LSM < 7 kPa is used as an indicator of non-significant liver histology but 12% of those who indeed had significant pathological lesions would be missed. In PIEALT patients with HBV DNA >= 20 000 IU/mL, the need for liver biopsy could be reduced by 53% with a false positive rate of 14% when LSM >= 7 kPa is used as a predictor of significant pathological lesions. Conclusion: The combination of serial ALT, viral load, and LSM appears to be a promising non-invasive tool. A management algorithm for HBeAg-negative patients comprising these noninvasive measures is proposed with liver biopsy being pursued in selected cases.