丙型肝炎肝硬化患者接受不同DAA方案的临床疗效与安全性的随访分析

摘要/Abstract

摘要： 目的比较不同直接抗病毒药物(DAA)治疗丙型肝炎肝硬化(CHCC)的疗效、安全性。方法纳入2022年1月至2024年6月空军军医大学第二附属医院收治的CHCC患者114例,采用的DAA方案包括索磷布韦联合利巴韦林(SOF组)、索磷布韦、雷迪帕韦联合利巴韦林(SOF+LDV组)及索磷布韦、达拉他韦联合利巴韦林(SOF+DCV组),比较各组疗效、治疗前后血生化指标及不良反应。结果 SOF+LDV组和SOF+DCV组早期病毒学应答、治疗结束时病毒学应答、持续病毒学应答均为100%,高于SOF组的37.5%、33.3%、31.2%(P<0.05)。治疗12周,SOF组HCV RNA、ALT、AST、LSM分别为(1.7±0.5)lg IU/mL、(38.5±4.4)U/L、(37.2±4.3)U/L及(13.2±2.3)kPa,SOF+LDV组分别为(1.2±0.4)lg IU/mL、(32.4±4.7)U/L、(32.0±4.9)U/L及(11.0±2.8)kPa,SOF+DCV组分别为(1.1±0.6)lg IU/mL、(31.7±5.0)U/L、(32.7±6.1)U/L及(10.4±3.0)kPa,差异有统计学意义(P<0.05)。不良反应均于治疗2周内发生,均自行改善。各组不良反应发生率比较,差异无统计学意义(χ²=0.349,P>0.05)。结论对丙型肝炎肝硬化患者而言,SOF+LDV和SOF+DCV方案具有更高的病毒学应答率和更显著的肝功能改善作用,且安全性良好。

关键词: 丙型肝炎肝硬化, 直接抗病毒药物, 持续病毒应答率, 索磷布韦

Abstract: Objective To compare the clinical data of patients with chronic hepatitis C cirrhosis (CHCC) treated with different direct-acting antiviral agents (DAAs), and evaluate their efficacy and safety. Methods 114 patients with CHCC admitted to the Second Affiliated Hospital of Air Force Medical University from January 2022 to June 2024 were included. The DAAs regimens adopted included sofebuvir combined with ribavirin (SOF group), sofebuvir, ledepavir combined with ribavirin (SOF+LDV group) and sofebuvir and daclatasir combined with ribavirin (SOF+DCV group). The therapeutic effects, blood biochemical parameters before and after treatment, and adverse reactions of each group were compared. Results In the SOF+LDV group and the SOF+DCV group, the early virological response, end-of-treatment virological response and sustained virology response were all 100%, significantly higher than those in the SOF group (37.5%, 33.3%, and 31.2%, respectively; P<0.05). Compared with the SOF group [(1.7±0.5) lg IU/mL, (38.5±4.4) U/L, (37.2±4.3) U/L, and (13.2±2.3) kPa], the SOF+LDV group [(1.2±0.4) lg IU/mL, (32.4±4.7) U/L, (32.0±4.9) U/L, and (11.0±2.8) kPa] and the SOF+DCV group [(1.1±0.6) lg IU/mL, (31.7±5.0) U/L, (32.7±6.1) U/L, and (10.4±3.0) kPa] showed statistically significant differences (P<0.05). All adverse events occurred within 2 weeks of treatment and resolved spontaneously. No statistically significant difference was observed in the incidence of adverse events among the groups (χ²=0.349, P>0.05). Conclusion SOF+LDV and SOF+DCV have higher virological response rate and more significant improvement of liver function in patients with CHCC, and their safety is good. The research results provide an important basis for the application of DAAs in patients with CHCC, and provide a reference for the selection of treatment schemes in clinical practice.

Key words: Chronic hepatitis C cirrhosis, Direct-acting antiviral agents, Sustained virological response, Sofosbuvir

李曼, 王瑞, 王苗苗, 汪春付, 杜倩. 丙型肝炎肝硬化患者接受不同DAA方案的临床疗效与安全性的随访分析[J]. 肝脏, 2026, 31(7): 958-961.

Li Man, Wang Rui, Wang Miaomiao, Wang Chunfu, Du Qian. Follow-up analysis of clinical efficacy and safety of patients with hepatitis C cirrhosis receiving different DAAs[J]. Chinese Hepatolgy, 2026, 31(7): 958-961.

/ 推荐

参考文献

[1] 柴晓哲, 朱霞峰, 骆成林, 等. 泛基因型与特异基因型DAAs方案精准治疗基因1b型慢性丙型肝炎患者疗效对比分析[J]. 实用肝脏病杂志, 2022, 25(3):355-358.
[2] Wedemeyer H, Di Marco V, Garcia-Retortillo M, et al. Global real-world evidence of sofosbuvir/velpatasvir as a highly effective treatment and elimination tool in people with hepatitis C infection experiencing mental health disorders[J]. Viruses, 2022, 14(11):2493.
[3] Tada T, Kurosaki M, Nakamura S, et al. Real-world clinical outcomes of sofosbuvir and velpatasvir treatment in HCV genotype 1- and 2-infected patients with decompensated cirrhosis: a nationwide multicenter study by the Japanese Red Cross Liver Study Group[J]. J Med Virol, 2021, 93(11):6247-6256.
[4] 丁国伟, 庞琳, 王晓春, 等. 2017—2019年哨点医院丙型肝炎基线特征及治疗现况分析[J]. 中华肝脏病杂志, 2020, 28(10):844-849.
[5] 张耀弟, 张月荣, 王慧, 等. 聚乙二醇干扰素 α 联合利巴韦林治疗丙型肝炎失败和复发患者的临床特征及直接抗病毒药物疗效观察[J]. 临床肝胆病杂志, 2019, 35(11):2456-2460.
[6] Banga J, Nizami S, Slim J, et al. Hepatitis C virus treatment response to ledipasvir/sofosbuvir among patients coinfected with HIV and HCV: real world data in a Black population[J]. Medicine (Baltimore), 2020, 99(11):e19140.
[7] Qi M, Yang M, Xu L, et al. Complete genome analysis identifies recombinant events and positive selection sites of hepatitis C virus from mainland China during 2010—2019[J]. Virus Res, 2021, 296:198354.
[8] 屈凌霄, 施阳, 陈恺韵, 等. 上海市2014—2019年丙型肝炎综合监测分析[J]. 中华流行病学杂志, 2021, 42(4):626-631.
[9] 中华医学会肝病学分会和感染病学分会. 《丙型肝炎防治指南》2019年更新版[J]. 实用肝脏病杂志, 2020, 23(1):S33-52.
[10] 中华预防医学会医院感染控制分会, 中华医学会感染病学分会, 中华预防医学会感染性疾病防控分会. 中国丙型病毒性肝炎医院感染防控指南(2021年版)[J]. 中国感染控制杂志,2021, 20(6):487-493.
[11] Matthew A N, Zephyr J, Nageswara Rao D, et al. Avoiding drug resistance by substrate envelope-guided design: toward potent and robust HCV NS3/4A protease inhibitors[J]. mBio, 2020, 11(2):172-191.
[12] 汤汝佳, 张宁, 周霞, 等. 直接抗病毒药物治疗肝移植术后丙型肝炎病毒感染受者的临床研究[J]. 中华肝胆外科杂志, 2021, 27(5):339-343.
[13] 黄爱龙, 袁正宏, 南月敏, 等. 乙型肝炎临床治愈策略:直接抗病毒药物[J]. 中华肝脏病杂志, 2020, 28(8):640-644.
[14] 魏来, 王琴. 直接抗病毒药物时代慢性丙型肝炎的治疗:不同方案选择的考虑[J]. 中华传染病杂志, 2018, 36(10):577-586.
[15] Bobardt M, Ramirez C M, Baum M M, et al. The combination of the NS5A and cyclophilin inhibitors results in an additive anti-HCV inhibition in humanized mice without development of resistance[J]. PLoS One, 2021, 16(5):e0251934.
[16] Barror S, Avramovic G, Oprea C, et al. HepCare Europe: a service innovation project. HepCheck: enhancing HCV identification and linkage to care for vulnerable populations through intensified outreach screening. A prospective multisite feasibility study[J]. J Antimicrob Chemother, 2019, 74(Suppl 5): v39-v46.
[17] Lin T, Wang X, Gao H, et al. Effect of hemodialysis on efficacy and pharmacokinetics of sofosbuvir coformulated with either daclatasvir or ledipasvir in patients with end - stage renal disease[J]. Blood Purif, 2020, 49(6):692-699.
[18] Ogawa E, Furusyo N, Nakamuta M, et al. Glecaprevir and pibrentasvir for Japanese patients with chronic hepatitis C genotype 1 or 2 infection: results from a multicenter, real - world cohort study[J]. Hepatol Res, 2019, 49(6):617-626.