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

肝脏 ›› 2024, Vol. 29 ›› Issue (8): 943-946.

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

崔蕊, 马杈, 杨天芬, 周浩军, 李萍萍

712000 陕西咸阳职业技术学院医学院(崔蕊);咸阳市第一人民医院消化内科(马杈),心血管内科(杨天芬),神经内科(周浩军);西安交通大学医学院第一附属医院转化医学中心(李萍萍)

收稿日期:2023-10-13 出版日期:2024-08-31 发布日期:2024-09-30
通讯作者: 杨天芬,Email:731243293@qq.com
基金资助:
陕西省重点研发计划项目(2022SF-460)

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

CUI Rui¹, MA Zhi², YANG Tian-fen³, ZHOU Hao-jun⁴, LI Ping-ping⁵

1. Xianyang Vocational and Technical College School of Medicine, Shaanxi 712000, China;
2. Department of Gastroenterology, First People’s Hospital of Xianyang, Shaanxi 712000, China;
3. Department of Cardiovascular Medicine, Xianyang First People’s Hospital, Shaanxi 712000, China;
4. Department of Neurology, Xianyang First People’s Hospital, Shaanxi 712000, China;
5. Translational Medicine Center, First Affiliated Hospital of Xi’an Jiaotong University School of Medicine, Shaanxi 710000, China

Received:2023-10-13 Online:2024-08-31 Published:2024-09-30
Contact: YANG Tian-fen,Email:731243293@qq.com

摘要/Abstract

摘要： 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(χ²=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。

关键词: 抗病毒药物(DAA), 慢性丙型肝炎, 基因型, 耐药相关替代突变(RAS)

Abstract: 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 (χ²=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.

Key words: Direct-acting antiviral drugs, Chronic hepatitis C, Genotype, Resistance-associated substitutions (RAS)

崔蕊, 马杈, 杨天芬, 周浩军, 李萍萍. 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[J]. 肝脏, 2024, 29(8): 943-946.

CUI Rui, MA Zhi, YANG Tian-fen, ZHOU Hao-jun, LI Ping-ping. Study on the clinical characteristics and genotype of direct-acting antiviral therapy failure in treatment of hepatitis C[J]. Chinese Hepatolgy, 2024, 29(8): 943-946.

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