Comparison of sequence changes of precore and core promoter regions in HBeAg-positive chronic hepatitis B patients with and without HBeAg clearance in lamivudine therapy

Abstract

The aim of this study was to compare the serial sequence changes of precore and core promoter regions in hepatitis B e antigen (HBeAg)-positive chronic hepatitis B (CHB) patients with and without HBeAg clearance in lamivudine treatment. Precore and core promoter genes of the hepatitis B virus (HBV) were sequenced from five serial serum samples of 74 HBeAg-positive CHB patients received lamivudine for 9-12 months (34 complete responders and 40 non-responders). Before lamivudine therapy, stepwise logistic regression analysis disclosed that ALT level > or =300 U/L, A1896 mutant, and log HBV DNA levels were the major determinants for complete response. In addition, Cox regression showed that age < 35 years and G1752 mutant were independent factors for sustained response. Compared with complete responders, a higher frequency of mutation in nucleotides 1773, 1802, 1803, 1845, 1850, and 1858 was found in the non-responders during therapy. Lamivudine therapy resulted in a further increase in T1762/1764 mutants and a further decrease in A1896 mutant during treatment and after HBeAg clearance in complete responders. T1762/A1764 mutation (not A1896) played an important role in lamivudine-induced HBeAg clearance. Moreover, T1773, C1802, G1803, T1846, A1850, and C1858 mutations might have significant correlation with HBeAg nonseroconversion.