直接抗病毒药物治疗慢性丙型肝炎患者疗效研究*

doi:10.3969/j.issn.1672-5069.2023.05.009

摘要/Abstract

摘要： 目的探讨应用直接抗病毒药物(DAAs)治疗慢性丙型肝炎(CHC)患者的疗效。方法 2019年6月～2022年1月我院诊治的CHC患者65例,给予所有患者索非布韦联合利巴韦林或索非布韦联合达拉他韦治疗12 w,随访24 w。计算天冬氨酸氨基转移酶/血小板比值指数(APRI)、基于4因子的纤维化指数,使用流式细胞仪检测外周血T淋巴细胞亚群,使用FibroScan诊断仪行肝脏硬度检测(LSM)。结果经肝穿刺活检,组织病理学检查诊断≤F2期肝纤维化者31例,≥F3期者34例;入组时,≤F2期与≥F3期CHC患者在年龄【分别为54(35,62)岁对60(51,67)岁】、LSM【分别为8.1(6.5,9.0)kPa对17.0(13.1,26.4)kPa】、APRI【分别为0.4(0.3,0.7)对0.9(0.6,1.4)】、FIB-4【分别为1.6(0.9,2.5)对3.7(2.4,5.2)】、PLT计数【分别为174(123,217)×10⁹/L对130(93,147)×10⁹/L】和AST【分别为76(56,79)U/L对62(47,67)U/L】方面,存在显著性差异(P<0.05);在随访结束时,本组65例CHC患者均获得SVR(100.0%);在基线、治疗结束和随访结束时,≤F2期CHC患者外周血CD4⁺细胞百分比分别为(34.6±2.8)%、(41.4±3.4)%和(44.8±3.7)%,CD4⁺/CD8⁺细胞比值分别为(1.1±0.2)、(1.3±0.3)和(1.6±0.4),≥F3期则分别为(34.3±3.0)%、(39.6±3.8)%和(41.8±3.7)%,和(1.1±0.3)、(1.4±0.3)和(1.6±0.4),均随着治疗而逐渐升高,但两组间无显著性差异(P>0.05)。结论 CHC患者存在不同程度的肝纤维化,应用DAAs治疗均可获得很好的疗效,其不仅具有直接抗病毒作用,可能还具有调节免疫功能紊乱作用。

关键词: 慢性丙型肝炎, 直接抗病毒药物, 持续病毒学应答, 肝纤维化, 治疗

Abstract: Objective The aim of this clinical trial was to investigate the virological response to direct acting antivirals (DAAs) in patients with chronic hepatitis C (CHC) and liver fibrosis. Methods 65 patients with CHC were encountered in our hospital between June 2019 and January 2022, all patients underwent liver biopsies at presentation, and the combination of sofosbuvir and ribavirin was given to 37 patients and the combination of sofosbuvir and daratavir was given to 28 patients, both lasting for 12 weeks. All the patients were followed-up for 24 weeks. The aspartate aminotransferase to platelet ratio index (APRI) and fibrosis index based on the 4 factors (FIB-4) were obtained, and the liver stiffness measurement (LSM) was measured by FibroScan. The peripheral blood lymphocyte subsets was determined by FCM. Results The liver histopathological examination showed that ≤F2 liver fibrosis in 31 cases and ≥F3 liver fibrosis in 34 cases in our series; at admission, there were significant differences as respect to the ages [54(35, 62) year old vs. 60(51, 67) year old], LSM [8.1(6.5, 9.0)kPa vs. 17.0(13.1, 26.4)kPa], APRI[ 0.4(0.3, 0.7) vs. 0.9(0.6, 1.4)], FIB-4[ 1.6(0.9, 2.5) vs. 3.7(2.4, 5.2)], PLT counts [174(123, 217)×10⁹/L vs. 130(93, 147)×10⁹/L] and AST levels [76(56, 79)U/L vs. 62(47, 67)U/L, all P<0.05] between patients with ≤F2 and ≥F3 liver fibrosis; at the end of 24 week follow-up, the sustained virologic response (SVR) was 100.0% in the 65 patients with CHC; at baseline, the end of treatment and end of follow-up, the percentages of peripheral blood CD4⁺ cells [(34.6±2.8)%, (41.4±3.4)% and (44.8±3.7)%] and the ratio of CD4⁺/CD8⁺ cells [(1.1±0.2), (1.3±0.3) and (1.6±0.4)] in patients with ≤F2 liver fibrosis were not significantly different compared to [(34.3±3.0)%, (39.6±3.8)% and (41.8±3.7)%] and [(1.1±0.3), (1.4±0.3) and (1.6±0.4)] in patients with ≥F3 liver fibrosis, although they both increased as the prolongation of the antiviral treatment. Conclusion The application of DAAs in the treatment of patients with CHC and different stage of liver fibrosis is efficacious, which not only by the direct antiviral action, but by the modulation of immune functions.

Key words: Hepatitis C, Direct acting antivirals, Sustained virological response, Liver fibrosis, Therapy

李亚玲, 杨发成, 蒋亚西. 直接抗病毒药物治疗慢性丙型肝炎患者疗效研究^*[J]. 实用肝脏病杂志, 2023, 26(5): 638-641.

Li Yaling, Yang Facheng, Jiang Yaxi. Virological response to direct acting antivirals in patients with chronic hepatitis C and liver fibrosis[J]. Journal of Practical Hepatology, 2023, 26(5): 638-641.

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直接抗病毒药物治疗慢性丙型肝炎患者疗效研究^*

Virological response to direct acting antivirals in patients with chronic hepatitis C and liver fibrosis

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