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目的明确临床实际工作中阿德福韦酯(ADV)治疗出现病毒学突破患者基因型耐药情况并对耐药相关因素进行分析。方法收集ADV治疗出现病毒学突破患者的血清样本及临床资料,应用PCR产物直接测序法联合焦磷酸测序法进行基因型耐药检测;分析基因型耐药与患者抗病毒治疗经过、基线HBV DNA载量等因素的相关性;并进一步分析rtA181T变异患者的病毒学及生化学指标变化。结果共收集106例ADV治疗出现病毒学突破患者,共检出基因型耐药45例,耐药位点67个;既往LAM等经治换用ADV患者ADV耐药检出率显著高于ADV初治患者(χ2=6.584,P=0.010);rtA181T耐药变异患者HBV DNA较最低值升高水平显著高于不包含rtA181T变异患者(t=566.000,P=0.014);包含rtA181T变异患者生化学突破率显著高于不包含rtA181T变异患者(χ2=5.140,P=0.023)。结论本组患者数据提示ADV治疗出现病毒学突破患者基因型耐药发生率约为40%,rtA181位点变异多于rtN236位点变异,rtA181T变异虽抑制耐药株病毒复制,但导致患者出现生化学突破几率并未减少。
Objective To clarify the genotypic resistance of patients with virological breakthrough in adefovir dipivoxil (ADV) treatment in clinical practice and analyze the factors related to drug resistance. Methods Serum samples and clinical data of patients with virological breakthrough in ADV were collected. Genotypes were detected by direct sequencing of PCR products combined with pyrosequencing. Genotype resistance and anti-viral treatment were analyzed in patients with baseline HBV DNA Quantity and other factors; and further analysis of rtA181T mutation in patients with virological and biochemical changes. Results A total of 106 ADV patients were enrolled in this study. A total of 45 drug resistance and 67 drug resistance loci were detected. The prevalence of ADV resistance in ADV patients with previous LAM was significantly higher than that in ADV patients (Χ2 = 6.584, P = 0.010). The HBV DNA levels in patients with rtA181T mutation were significantly higher than those without rtA181T mutation (t = 566.000, P = 0.014). The patients with rtA181T mutation had higher levels of HBV DNA than the patients with rtA181T mutation Rates were significantly higher than those without rtA181T mutation (χ2 = 5.140, P = 0.023). Conclusions The data of this group suggest that the prevalence of genotypic drug resistance in ADV patients is about 40%, the mutation of rtA181 is more than that of rtN236, and the mutation of rtA181T inhibits the replication of drug-resistant strains, Chemical breakthrough probability has not diminished.