接受核苷(酸)类似物治疗的慢性乙型肝炎患者HBV逆转录酶区耐药变异危险因素分析

Analysis of risk factors for drug resistant mutations in the reverse transcriptase region in chronic hepatitis B virus-infected patients

目的分析可能影响慢性HBV感染者逆转录酶(RT)区变异的危险因素。方法回顾性收集2016年1月1日至2016年12月31日于天津市第二人民医院门诊和住院行HBVRT变异基因检测的慢性HBV感染者678例,其中诊断符合慢性乙型肝炎者417例,肝硬化219例,原发性肝癌患者42例。未使用任何抗病毒治疗者268例,曾用抗病毒治疗停药6个月及以上者138例,持续抗病毒治疗者272例。HBV基因分型及RT区变异位点采用直接测序法检测。对可能影响HBV RT区耐药基因变异的危险因素,包括年龄、基因型、抗病毒药物选择以及用药时间、HBV感染情况、生物化学指标等进行单因素分析,筛选出独立危险因素。结果678例HBV感染者中有290例检测出RT区变异(42.8%),其中,预存耐药率为6.72%,经治患者耐药变异率为23.19%。持续抗病毒治疗者耐药变异率为66.18%。抗病毒治疗1~5年的慢性HBV患者发生基因突变的比例最高为27.14%。对可能导致HBV变异的因素进行logistic回归分析结果显示,高龄、初治时核苷类药物的选择及用药时间等是影响HBV RT区变异的主要因素。结论丙氨酸转氨酶异常程度、HBV基因型、HBV DNA定量水平不是耐药变异的主要影响因素。年龄超过60岁、长期使用低耐药屏障的核苷类药物为HBV耐药发生高风险人群,应加强HBV耐药监测。

Objective To analyze the risk factors that may affect the mutations in the reverse transcriptase region in chronic hepatitis B virus-infected patients.Methods 678 hospitalized cases with chronic HBV infection who underwent HBV RT testing at Tianjin Second People's Hospital from January 1,2016 to December 31,2016 were collected retrospectively.Among them,417 cases were diagnosed with chronic hepatitis B,219 cases with liver cirthosis and 42 cases with primary liver cancer.There were 268 cases of non-use of any antiviral therapy,138 cases of discontinuation of antiviral drugs for 6 months or more,and 272 cases of continuous antiviral therapy.HBV genotyping and RT region mutation sites were detected by direct sequencing.The risk factors that may affect the drug resistant mutation in the HBV RT mutation,including age,genotype,antiviral drug selection and medication time,hepatitis B virus infection,and biochemical markers were analyzed by univariate analysis to screen out independent risk factors.Results Among 678 HBV-infected cases,290 cases(42.8%)were detected with RT-region mutation.Among them,the pre-existing drug resistant rate was 6.72%,and the drug resistant mutation rate was 23.19%in treated patients.The drug resistant mutation rate of patients with continuous antiviral therapy was 66.18%.Gene mutations highest rate for 1~5 years was 27.14%in chronic HBV patients treated with antiviral therapy.Logistic regression analysis of the factors that had led to HBV mutation showed that old age,the selection of nucleoside drugs at the beginning of treatment and medication time were the main factors affecting HBV RT mutations.Conclusion Abnormal ALT level,HBV genotype,HBV DNA quantitative level are the main factors infuencing non drug resistant mutations.Age over 60 years old,and long-term use of low-barrier nucleoside drugs are high-risk groups for HBV resistant.Therefore,HBV resistant monitoring should be strengthened.