Analysis Of Hepatitis B Virus Resistance Genemutations In Chronic Hepatitis B Patients On Drug Combination

Objective:In the study, we make three groups:combined use of lamivudine and entecavir, lamivudine single used, entecavir single used. We compared HBV-DNA levels of serum, YMDD Genetic mutations and changes of genotypes before and after treatments. We made basis for clinical reasonable provide and reference for treatment against hepatitis b virus.Methods:1 One hundreds fifty patients with chronic hepatitis B who were HBe Ag positive but not detected the variation of HBV-YMDD and HBV-DNA before treatment were divided into combination medicine group of 50 patients, simple medicine group 1 of 50 patients, simple medicine group 2 of 50 patients. The combination medicine group were treated with entecavir orally 0.5mg once daily combined with lamivudine orally 50 mg once daily, while the medicine group 1 were treated with lamivudine orally 100 mg once daily and simple medicine group 2 were treated with lamivudine orally 1mg once daily.2 The T lymphocyte subsets in peripheral blood, negative conversion ratio of HBe Ag and HBV DNA, HBV-YMDD mutations, HBV genotypes, RT sites mutations were measured respectively at baseline,6 months,12 months, 18 months,24 months.3 The t-test and Chi-square were used in analyzing the date by statistical soft 16.0.The three groups of cases were analyzed by repetitive measurement deviation analysis and four space form card square examination.Results:1 Three groups had no YMDD variation before and after treatment. After treatment, YMDD mutation rate gradually increased. There are significant differences among three groups. The YMDD mutation rates of the combination group were lower than the single drug group 1 and group 2 in different clinical stages. But there are no significant differences between the combination group and single drug group 2 and there are significant differences between the combination group and single drug group 1. The YMDD mutation rates of the single drug group 2 were lower than the single drug group 1 in different clinical stages. There are significant differences between single drug group 1 and single drug group.2 Negative conversion rate of HBV-DNA increased gradually by the treatment, during a 24-months-treatment, we got statistically significant differences in all of the 3 groups(P<0.05).3 Negative conversion rate of HBe Ag increased gradually by the treatment. Also, in every medication period we got statistically significant differences among union medication group and both single medication groups(P<0.05).4 There is no statistically significant difference in CD4+Tcell, CD8+Tcell, CD4+/CD8+ of blood before treatment(P>0.05), CD4+Tcell and CD4+/CD8+ of blood was increasing after 6,12,18,24 months of treating while CD8+Tcell was decreasing. We got statistically significant differences in all of the 3 groups by making repeated measures data of ANOVA(P<0.001), and statistically significant differences within every group(P<0.001).5 At the time of 24 months, rt L180M+M204V, rt L180M+M204I and rt M204 I made resistance mutations in single medication group 1, while it was rt T184 L, rt T184 S, rt T184L+M204V, rt S202 G and rt M250 L in single medication group 2, and rt T184L+L180M+M204V, rt T184L+S202G+ L180 M + M204 V, rt M250L+M204I in union medication group. At the time of 24 months,we got statistically significant differences of mutation rate in all of the 3 groups(χ2 =24.72, P<0.01).Conclusions:1 It could improve the peripheral blood T cell subsets, improve the cellular immune function, inhibit HBV-DNA copies, increase negative conversion rate of HBe Ag and reduce HBV-YMDD variation more effectively by union medication treatment than single medication treatment.2 The early united use of lamivudine and entecavir made less number of mutation compared with single use entecavir or lamivudine treated with chronic hepatitis B patients.3 It is rt M204 I that made most resistance in single use lamivudine group, followed by rt L180M+M204V and rt L180M+M204I. It was rt T184L/S and rt T184L+M204V, followed by rt S202 G and rt M250 L in single use entecavir group. In union medication treatment group, it were rt T184L、L180M+ M204V、 rt M250L+ M204 I and rt T184L+S202G+L180M+M204V.4 There is no statistically significant difference in the detection rate of drug resistance between single drug and drug combination group in B and C genotypes.