Objective: To explore YMDD and HBeAg related mutations of hepatitis B virus and its clinical significance during lamivudine therapy.
Methods: From sera of chronic hepatitis B patients with 9 - 30 months lamivudine therapy, signal-base mutations of YMDD motif, G1896A, A1814C, A1762T and G1764A were analyzed by gene chips technique.
Results: In the 102 patients with 18 months in average of lamivudine treatment, 22 were found to have YMDD mutations, including 8 with YMDD and HBeAg related mutants. 3 of the 8 patients had G1896A mutant, 2 had A1814C and the remaining had G1896A + A1814C, A1762T and G1764A, A1762T and G1764A + G1896A. The former 5 patients and signal YMDD mutant patients were HBeAg positive, while the latter 3 with YMDD and HBeAg related multiple mutants were HBeAg negative. One of the three patients with multiple mutants who continued lamivudine treatment 3 months more reversed to YMDD wide-type HBV with accompanying positive HBeAg.
Conclusions: Mutant of YMDD associated with HBeAg related multiple mutations during lamivudine treatment may arise in patients with HBV DNA breakthrough and negative HBeAg. HBV DNA should be detected in the patients with HBeAg seroconversion to exclude the HBeAg related multiple mutations.