直接抗病毒药物治疗慢性终末期肾病合并慢性丙型肝炎患者疗效初步研究*

doi:10.3969/j.issn.1672-5069.2023.05.010

摘要/Abstract

摘要： 目的观察应用直接抗病毒药物(DAAs)治疗慢性终末期肾病(ESRD)合并慢性丙型肝炎(CHC)患者的疗效和安全性。方法 2015年1月～2021年1月我院诊治的ESRD合并CHC患者26例,其中初治的ESRD合并CHC患者20例,α-干扰素联合利巴韦林经治患者6例,1b、2a、3b和6a型HCV感染者分别为9例、5例、6例和6例。均接受索磷布韦(200 mg.d^-1)联合达卡他韦(90 mg.d^-1)连续治疗24 w。评估治疗第4 w快速病毒学应答(RVR)、治疗结束病毒学应答(ETVR)、停药后6个月病毒学应答(SVR6)和停药12个月病毒学应答(SVR12)。结果各HCV基因型感染者RVR、ETVR、SVR6和SVR12为100.0%,除了基因3b型感染患者SVR6和SVR12均为83.3%,其中1例在停药后病情复发;治疗前,初治患者血清HCV RNA载量为4.4(0.8,7.4)×10⁶IU/ml,经治患者为4.0(0.6,6.0)×10⁶IU/ml,差异具有统计学意义(P<0.05);经DAAs抗病毒治疗后,初治患者SVR为95.0%,经治患者为100.0%,差异无统计学意义(P>0.05);在治疗前,26例CHC患者血清ALT水平为92(57,109)U/L,AST水平为86(54,97)U/L,在治疗后均恢复正常【分别为27(19,31)U/L和19(17,28)U/L,P<0.05】,而sCr无显著变化【286.2(176.0,391.2)μmol/L对282.4(177.8,387.9)μmol/L,P>0.05】;在治疗过程中,共有8种(43例次)药物相关不良事件发生,包括恶心38.5%、乏力38.5%、食欲不振30.8%、高钾血症26.9%、关节疼痛11.5%、低血糖7.7%、高血压7.7%和血尿3.8%。结论应用索磷布韦联合达卡他韦治疗ESRD合并CHC患者安全、有效,值得进一步观察。

关键词: 丙型肝炎, 慢性终末期肾病, 直接抗病毒药物, 索磷布韦, 达卡他韦, 治疗

Abstract: Objective The aim of this study was to observe the direct acting antivirals (DAAs) in treatment of patients with chronic end-stage renal disease ((ESRD)) and concomitant hepatitis C virus infection. Methods 26 patients with ESRD and concomitant chronic hepatitis C (CHC) were enrolled in our hospital between January 2015 and January 2021, including 20 naïve cases and 6 peg-interfoeron-α2a and ribavirin combination treated cases. The patients with CHC had 1b infection in 9 cases, 2a infection in 5 cases, 3b infection in 6 cases and 6a infection in 6 cases. All patients received sophorbuvir (200 mg.d^-1) and daclatavir (90 mg.d^-1) combination anti-viral treatment for 24 weeks. The rapid virological response (RVR), end of treatment virological response (ETVR), sustained virological response at six month discontinuation (SVR 6) and SVR at 12 month discontinuation (SVR12) were recorded. Results The RVR, ETVR, SVR6 and SVR12 in all patients with different HCV genotype infection were 100.0%, except for in patients with 3b infection, in which the SVR6 and SVR12 were 83.3%, as one patients had relapse after discontinuation of DAA treatment; at admission, serum HCV RNA loads in naïve patients was 4.4(0.8,7.4)×10⁶IU/ml, much higher than 4.0(0.6, 6.0)×10⁶IU/ml in re-treated patients (P<0.05); after DAAs antiviral treatment, the SVR in naïve patients was 95.0%, not significantly different compared to 100.0% in re-treated patients (P>0.05); at admission, serum ALT and AST levels in 26 CHC patients were 92(57, 109)U/L and 86(54, 97)U/L, both got back to normal [27(19, 31)U/L and 19(17, 28)U/L, P<0.05] after treatment, while serum Cr levels had no significant changes [286.2(176.0, 391.2)μmol/L vs. 282.4(177.8, 387.9)μmol/L, P>0.05] in our series; during the period of antiviral treatment, there were eight kinds(43 case times)of DAAs-related untoward effects, including nausea in 38.5%, fatigue in 38.5%, anorexia in 30.8%, hyperkalemia in 26.9%, arthralgia in 11.5%, hypoglycemia in 7.7%, hypertension in 7.7% and hematuresis in 3.8%. Conclusion The DAAs regimen by fosbuvir and daclatasvir combination is efficacious and safe in treatment of patients with ESRD and CHC, which warrants further clinical investigation.

Key words: Hepatitis C, Chronic end-stage renal disease, Direct acting antivirals, Sophorbuvir, Daclatasvir, Therapy

蔡涛, 魏玮, 王欣雯, 王玥坤, 秦军, 蓝晓红. 直接抗病毒药物治疗慢性终末期肾病合并慢性丙型肝炎患者疗效初步研究^*[J]. 实用肝脏病杂志, 2023, 26(5): 642-645.

Cai Tao, Wei Wei, Wang Xinwen, et al. Direct acting antivirals in treatment of patients with chronic end-stage renal disease and concomitant hepatitis C virus infection[J]. Journal of Practical Hepatology, 2023, 26(5): 642-645.

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直接抗病毒药物治疗慢性终末期肾病合并慢性丙型肝炎患者疗效初步研究^*

Direct acting antivirals in treatment of patients with chronic end-stage renal disease and concomitant hepatitis C virus infection

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