直接抗病毒药物治疗失败的慢性丙型肝炎患者临床特点及基因型分析

Study on the clinical characteristics and genotype of direct-acting antiviral therapy failure in treatment of hepatitis C

目的探索直接抗病毒药物(DAA)治疗失败的慢性丙型肝炎(CHC)患者的临床特点及基因型特征。方法选取2021年9月至2022年12月咸阳市第一人民医院DAA治疗失败的患者28例,同时期DAA治疗成功者100例。酶法检测肝功能、PCR-反向杂交法检测HCV基因型、Sanger测序法检测耐药相关替代突变(RAS)片段,分析DAA观察组患者临床特征及基因型特点。结果失败组和有效组HCV RNA>105 IU/mL分别为23例(82.1%)、34例(34.0%),差异有统计学意义(χ^(2)=20.526,P=0.001)。DAA治疗失败组男性患者TBil、DBil分别为14.61(10.98,20.78)μmol/L、4.94(3.08,7.48)μmol/L,均高于女性患者的6.65(4.90,8.40)μmol/L、2.50(1.78,3.07)μmol/L(Z=-2.018和-2.456,均P=0.01)。纳入患者共检测出3种HCV基因型,分别为1b、2a及3b,有26例未测出基因型,失败组HCV 1b、2a及3b基因型分别为11例(39.3%)、6例(21.4%)及5例(17.8%),有效组分别为56例(56.0%)、15例(15.0%)及9例(9.0%)。失败组检测出NS5A和NS5B2种基因片段,但是RAS发生率不同。结论DAA治疗失败者会受性别、病毒载量、基因型以及RAS种类影响。

Objective To explore the clinical and genotypic characteristics of patients with chronic hepatitis C(CHC)who experienced treatment failure with direct-acting antiviral drugs(DAAs).Methods Between September 2021 and December 2022,28 patients who failed in DAA treatment in our hospital were selected as the observation group,and 100 patients who succeeded in DAA treatment in the same period were selected as the control group.Liver function was detected by enzyme method,hepatitis C virus(HCV)genotype was detected by PCR-reverse hybridization method,and drug resistance-associated substitution mutation(RAS)fragment was detected by Sanger sequencing method.The clinical characteristics and genotype characteristics of patients in DAA observation group were analyzed.Results There were 23 cases(82.1%)and 34 cases(34.0%)with HCV-RNA load>105 IU/ml in the observation group and the control group respectively,and the difference was statistically significant(χ^(2)=20.526,P=0.001).In DAA treatment observation group,the TBIL and DBIL of male patients were 14.61(10.98-20.78)μmol/L and 4.94(3.08-7.48)μmol/L,respectively,which were significantly higher than those of female patients[6.65(4.90-8.40)μmol/L and 2.50(1.78-3.07)μmol/L,Z=-2.018,-2.456,P=0.010 and 0.010,respectively].Three HCV genotypes were detected in the included patients,namely 1b,2a and 3b,and 26 of them were undetected.HCV 1b,2a and 3b genotypes in the observation group were 11(39.3%),6(21.4%)and 5(17.8%),of while in the control group were 56(56.0%),15(15.0%)and 9(9.0%),respectively.NS5A and NS5B2 gene fragments were detected in DAA treatment observation group,but the incidence of RAS was different.Conclusion Patients who experience DAA treatment failure are influenced by factors such as patient gender,viral load,genotypic variations,and types of RAS.