Long-term Outcome of HBV Carriers with Negative HBe Antigen and Normal Aminotransferase

Purposes To elucidate the incidence of hepatitis activation and hepatocellular carcinogenesis in patients with negative HBe antigen and normal aminotransferase, long-term observation was performed in a retrospective cohort. Methods Among 116 consecutive patients with normal aminotransferase and negative HBe antigen at the time of liver biopsy, sequential frozen sera for initial 5 years were available for 95 patients. Hepatitis B virus (HBV) DNA assay (sensitivity >400 copy/mL) and aminotransferase were annually examined in the initial 5 years after biopsy. Results Liver biopsy showed minimal hepatitis (F0) in 9, F1 in 53, F2 in 21, F3 in 6, and F4 or cirrhosis in 6. Initial HBV DNA concentration was low (less than 104 copies/mL) in 33, intermediate (104-106) in 53, and high (106 or more) in 9. Hepatitis activation rates with twice as high as normal aminotransferase at the end of the third year were 12.1% in the low DNA group, 43.4% in the intermediate group, and 66.7% in the high DNA group. Initial HBV DNA values were significantly associated with future increase in aminotransferase (P<.0001). Initial DNA, history of aminotransferase elevation, and histological staging independently affected future hepatitis activation. Carcinogenesis rate in patients with and without high DNA of 106 copies/mL during the initial 3 years were 6.9% and 0%, respectively, at the end of the 5th year, and 11.5% and 1.8%, respectively, at the 10th year, (P = .021). Conclusion Advanced stages of hepatitis were sometimes found in HBe antigen-negative, aminotransferase-normal HBV carriers. Serial HBV DNA assessment in early 3 years predicted future hepatitis activation and carcinogenesis.