慢乙肝患者基因变异位点检测及阿德福韦酯疗效观察

摘要

目的 探讨乙型肝炎病毒基因突变的类型及位点,观察阿德福韦酯的临床疗效.方法 43例慢性乙型肝炎位点变异患者服用阿德福韦酯10 mg/d,48周,观察治疗前后临床指标的变化.结果 变异位点为rtL180M/M204V、rtM204I、rtL180M/M204I 28例,单独与联合变异并存；G1896A变异7例,V214A、V173L变异4例,G1896A、L180M、M204I、M204V联合变异4例.阿德福韦酯对HBV变异株有明显的抑制作用,HBV DNA由治疗前与治疗后24周、48周HBV DNA、ALT复常率显著改善(P值均＜0.01).药物安全性良好.结论 阿德福韦酯对位点变异慢乙肝患者有一定疗效.%Objective To investigate the mutation type and sites of HBV DNA and the therapeutic effects of adefovir dipivoxil(ADV) on patients with chronic hepatitis B(CHB). Methods HBV DNA was amplified by PCR. The PCR products were sequenced using Prosequence 96MA sequenator. The sequencing data were analyzed by sequencing software. Forty-three CHB patients with multi-mutation were Treated by ADV 10 mg daily for 48 weeks. The clinical data before and after switch were collected. Results Ttwenty-eight patients were found to have YMDD mutations. The mutation types were rtL180MM204V ,rtM204I、rtL180M/ M204I. Single mutation and multi-mutation were found at the same time. Seven patients had G1896A mutant, 4 had V214A、V173L mutant and 4 had G1896A、L180M,M204I,M204V multi-mutation. ADV could significantly suppress the replication of HBV mutant strain. HBV DNA level was decreased from (6.28 ± 1.09) log10 copy/ml before switch to (4.14 ± 1.02)log10 copy/mland (3.91 ± 0.85) log,0 copy/ml after switch to ADV for 24 and 48 weeks. Alanine aminotransferase normalization rate were 51.1%, 67.4% at 24 and 48 weeks (all P< 0.01). No adverse events were found by detecting blood routine, urine routine, renal function after treatment with ADV. Conclusions ADV is effective on CHB patients with multi-mutation.