Researches On Lamivudine-induced YMDD Mutant Of Different Genotypes Of Hepatitis B

Objective:To evaluate the features of Lamivudine (LAM)-induced YMDD mutant among differnent genotypes of HBV virus and investigate the relationship between HBeAg and YMDD mutant. Methods:A cohort study about YMDD mutation of HBV virus in patients with lamivudine treatment had been carried out. Serum samples were obtained from 94 patients chronically infected with HBV. All the patients had received mono-LAM treatment. During the 6 months investigations, YMDD mutation was detected using primer-specific real-time PCR and HBV DNA. ALT, AST and HBeAg were detected for every 3 months. The YIDD/YVDD features in different genotypes of Hepatitis B virus were compared. The relationships between the mutant rate and the three possible influencing factor (therapy time, duration of infection and the age of patients) were disclosed.Results:The results are listed as follows:(1) In a time period of 6 months investigations, YMDD was detected in 39 of 91 subjects. Six of them were in B genotype, 24 in C genotype,9 in B+C genotype. The incidence rate of YMDD mutation was higher in C genotype than B+C genotype, while the HBV virus of B genotype showed lowest mutation rate (P<0.05). (2) The distribution of YMDD mutant types in different genotypes of HBV was:4 YIDD,2 YVDD in B genotypes of HBV; 4 YIDD,4 YVDD in B+C genotypes of HBV; 10 YIDD,9 YVDD in C genotype of HBV. (3) There was no difference in ALT lever and HBV DNA load of patients with YMDD mutant HBV virus of different genotype (P>0.05). (4) YMDD mutant were detected in 39 of 91 follow-up cases, for those carriers of mutant HBV virus,9 patients received LAM treatment within 1 year.14 patients received LAM treatment with a time period of 1-2 years,16 patients had LAM treatment for more than 2 years. The incidence rate of mutation was closely associated with the time of LAM therapy. However, the incidence rate of mutation has no association with duration of infection. (5) YIDD/YVDD mutant was detected in 26 of 62 HBeAg positive subjects (YIDD positive 15 and YVDD positive 11), and in 7 of 29 HBeAg negative subjects (YIDDpositive 2 and YVDDpositive 5) (6 YIDD/YVDD mutant co-existing subjects were picked out for analysis). The incidence rate of YIDD mutant was higher in HBeAg positive subjects than that in in HBeAg negative subjects (P<0.05). While the incidence rate of YVDD mutant exhibited no any difference in HBeAg positive subjects than that in HBeAg negative subjects (P>0.05). Conclusion:During long term of LAM therapy, the incidence rate of YMDD mutation was higher in C genotype than B+C genotype, while the Bgenotype showed lowest mutation rate. The mutation rate went up with prolong use of LAM. The mutation rate was not associated with duration of infection and the age of patients. The distribution of YMDD mutant types showed no variations in different genotypes of HBV. And the carriers of YMDD mutant virus of different HBV genotypes showed no diference in HBV DNA and ALT than thethose of wild virus. YIDD mutant strains tended to be harbored in HBeAg positive serum. YVDD mutant strains had no associations with HBeAg status. Gender, age, HBeAg status, serum viral load, the state of disease and duration of infection were also not associated with spontaneous YMDD mutation.