慢性乙型肝炎患者拉米夫定耐药模式及耐药后体内免疫环境的改变

目的探讨慢性乙型肝炎患者发生拉米夫定耐药常见的模式及耐药后体内免疫环境的改变。方法应用PCR及基因测序方法回顾性分析72例发生拉米夫定耐药患者血清HBVDNA多聚酶区基因变异模式,比较72例患者拉米夫定抗病毒6个月时及耐药后血清INF-γ、IL-2、IL-4因子水平与对照组细胞因子的水平差异。结果拉米夫定耐药4种主要的突变模式分别为：单位点rtM204I突变,占34.7%（25/72）;rtL180M＋rtM204V,占30.56%（22/72）;rtL180M＋rtM204I,占16.67%（12/72）;rtV173L＋rtV180M＋rtM204V,占12.5%（9/72）;抗病毒6个月时,未变异组与对照组IL-2（P=0.20）、IFN-γ（P=0.14）、IL-4（P=0.119）水平差异无统计学意义。耐药组HBVDNA发生病毒变异后,IL-2、IFN-γ水平显著低于对照组（P〈0.01）,而IL-4水平则高于对照组（P〈0.01）,差异有统计学意义。结论慢性乙型肝炎应用拉米夫定抗病毒治疗耐药模式主要是rtM204I突变及rtL180M、rtV173L、rtM204V、rtM204I联合变异,发生耐药后慢性乙型肝炎患者体内免疫环境将从Th1优势应答转换为Th2优势应答。

The Modle of HBVDNA Mutation and the Change of Immune Environment in the Chronic Hepatitis B Patients after Lamivudine Resistance

Objective To research the modle of HBVDNA mutation and the change of immune environment in the Chronic hepatitis B patients after Lamivudine resistance.Methods We analysised the HBVDNA P gene mutation of chronic hepatitis B after Lamivudine resistance use Polymerase chain reaction and gene Sequencing,compared the level of INF-γ、IL-2、IL-4 in the hepatitis B patient＇s serum whose HBVDNA mutated with control group on the sixth Treatment Month and after the mutation occurred.Results The main modle of HBVDNA mutation were the follows：the mutation on gene rtM204I account for 34.7%,rtL180M＋rtM204V account for 30.56%,rtL180M＋rtM204I account for16.67%,rtV173L＋rtV180M＋rtM204V account for 12.5%。There were no difference between the level of INF-γ、IL-2、IL-4 factors of the two groups on the sixth treatment month,the level of IL-2、IFN-γin mutation group were lower than the control group,the level of IL-4 was higher than the control group.Conclusion The modle of HBVDNA mutation were the mutation rtM204I and the combine variation on rtL180M、rtV173L 、rtM204V、rtM204I gene,the predominant immune environment in the Chronic hepatitis B patients after Lamivudine resistance would change from Th1 to Th2.