利托那韦增强的达诺瑞韦联合索磷布韦和利巴韦林方案治疗基因3型慢性丙型肝炎患者疗效和安全性研究*

doi:10.3969/j.issn.1672-5069.2025.04.011

摘要/Abstract

摘要： 目的初步研究应用利托那韦(RTV)增强的达诺瑞韦(DNVr)联合索磷布韦(SOF)和利巴韦林(RBV)方案治疗基因3型感染的慢性丙型肝炎(CHC)患者的近期疗效和安全性。方法 2021年1月～2023年12月我院收治的96例基因3型感染CHC患者被随机分为对照组48例和观察组48例,分别采用SOF联合达拉他韦(DCV)和RBV治疗或RTV增强的DNVr联合SOF和RBV治疗12周,随访12周。采用荧光定量RT-PCR法检测血清HCV RNA,使用流式细胞仪检测外周血淋巴细胞亚群。结果观察组快速病毒学应答(RVR)、早期病毒学应答(EVR)、治疗结束病毒学应答(ETVR)和持续病毒学应答(SVR)率分别为89.6%、95.8%、100.0%和91.7%,均显著高于对照组的66.7%、75.0%、81.3%和75.0%(P＜0.05);在治疗12周结束时,观察组血清ALT和AST复常率分别为95.8%和100.0%,与对照组的91.7%和93.8%比,无显著性统计学差异(P＞0.05);两组外周血CD4⁺细胞百分比和CD4⁺/CD8⁺细胞比值较治疗前上升,而CD8⁺细胞百分比较治疗前下降(P＜0.05),但两组比较无显著性差异(P＞0.05);在治疗期间两组发生的不良反应包括腹泻、恶心、发热、脱发和皮疹等,但两组不良反应发生率比较无显著性差异(27.1%对31.3%,P＞0.05)。结论应用RTV增强的DNVr联合SOF和RBV方案治疗基因3型感染的CHC患者可显著提高SVR,可能与改善了免疫功能紊乱有关,值得临床扩大验证。

关键词: 丙型肝炎, 基因3型丙型肝炎病毒, 利托那韦, 达诺瑞韦, 索磷布韦, 利巴韦林, 治疗

Abstract: Objective The aim of this study was to investigate efficacy and safety of ritonavir (RTV)-boosted danoprevir (DNVr) with combination of sofosbuvir (SOF) and ribavirin (RBV) regimen in the treatment of patients with chronic hepatitis C (CHC) and viral genotype 3 infection. Methods 96 patients with HCV genotype 3 infected CHC were admitted to our hospital between January 2021 and December 2023, and were randomly assigned to receive SOF with combination of daclatasvir (DCV) and RBV in 48 cases in control group, and to receive DNVr with combination of SOF and RBV treatment in another 48 patients in the observation for 12 weeks. All patients were followed-up for 12 weeks after discontinuation of antiviral therapy. Serum HCV RNA loads was assayed by fluorescence quantitative PCR, and peripheral blood lymphocyte subsets were detected by flow cytometry. Results Rapid virological response, early virological response, end of treatment virological response and sustained virological response rates in the observation group were 89.6%, 95.8%, 100.0% and 91.7%, all significantly higher than 66.7%, 75.0%, 81.3% and 75.0% (P＜0.05) in the control; by end of 12-week treatment, serum ALT and AST normalization rates in the observation were 95.8% and 100.0%, both not much different as compared to 91.7% and 93.8% in the control (P＞0.05); percentages of peripheral blood CD4⁺ cells and CD4⁺/CD8⁺ cell ratios in the two groups elevated, while percentages of CD8⁺ cells decreased compared to those at presentation(P＜0.05), and there were no significant differences between the two groups (P＞0.05); during treatment, incidences of adverse effects, such as diarrhea, nausea, fever, lipsotrichia and rash in the two groups were not much different(27.1% vs. 31.3%, P＞0.05). Conclusion The DNVr with combination of SOF and RBV regimen in treatment of patients with CHC and HCV genotype 3 infection is short-termly efficacious and safe, which might be related to improve of immune functions besides suppression of viral replication.

Key words: Hepatitis C, Hepatitis C viral genotype 3, Ritonavir, Danoprevir, Sofosbuvir, Ribavirin, Therapy

林丽泉, 白晓苏, 张爱兰, 程小桂. 利托那韦增强的达诺瑞韦联合索磷布韦和利巴韦林方案治疗基因3型慢性丙型肝炎患者疗效和安全性研究^*[J]. 实用肝脏病杂志, 2025, 28(4): 521-524.

Lin Liquan, Bai Xiaosu, Zhang Ailan, et al. Efficacy and safety of ritonavir-boosted danoprevir with combination of sofosbuvir and ribavirin regimen in the treatment of patients with chronic hepatitis C and viral genotype 3 infection[J]. Journal of Practical Hepatology, 2025, 28(4): 521-524.

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利托那韦增强的达诺瑞韦联合索磷布韦和利巴韦林方案治疗基因3型慢性丙型肝炎患者疗效和安全性研究^*

Efficacy and safety of ritonavir-boosted danoprevir with combination of sofosbuvir and ribavirin regimen in the treatment of patients with chronic hepatitis C and viral genotype 3 infection

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