直接抗病毒药物治疗肾移植术后丙型病毒性肝炎疗效与安全性的临床观察

牛英; 明英姿; 佘兴国; 刘洪

doi:10.3969/j.issn.1674-7445.2017.01.010

直接抗病毒药物治疗肾移植术后丙型病毒性肝炎疗效与安全性的临床观察

doi: 10.3969/j.issn.1674-7445.2017.01.010

410013 长沙，中南大学湘雅三医院器官移植科

基金项目:

吴阶平医学基金会临床科研专项资助基金 320.6750.15070

详细信息

通讯作者:
牛英，Email：niuying1@aliyun.com

中图分类号: R617, R512.6+3
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出版历程
- 收稿日期: 2016-10-12
- 网络出版日期: 2021-01-19
- 刊出日期: 2017-01-15

Preliminary observation of clinical efficacy and safety of direct-acting antiviral agents for hepatitis C virus following renal transplantation

Department of Organ Transplantation, the 3^rd Xiangya Hospital of Central South University, Changsha 410013, China

More Information

Corresponding author: Niu Ying, E-mail:niuying1@aliyun.com

摘要

摘要: 目的观察直接抗病毒药物（DAAs）治疗肾移植术后丙型病毒性肝炎的疗效与安全性。方法 6例肾移植术后单纯合并丙型肝炎病毒（HCV）患者，肾移植术后时间为8~43个月（中位时间19个月），治疗前HCV病毒载量为4.03×10³~8.18×10⁷ IU/mL，免疫抑制方案为他克莫司（FK506）+吗替麦考酚酯（MMF）+泼尼松（Pred）（4例）或环孢素（CsA）+MMF+Pred（2例），治疗前血清肌酐水平低于200 μmol/L，且尿量、体质量稳定，抗病毒治疗前6个月内无重大精神刺激及创伤史。6例患者抗病毒治疗前均未行HCV病毒基因型监测，口服DAAs治疗方案为单药索非布韦（4例）、索非布韦+雷迪帕韦（1例）、索非布韦+达卡他韦（1例），疗程均为12周，治疗期间每周检测患者的全血细胞计数、血清转氨酶、肌酐、免疫抑制剂血药浓度水平，每4周检测血清HCV RNA定量。结果 6例患者中，5例患者在治疗4周时HCV RNA定量即转阴并于疗程结束后获得持续性病毒学应答（SVR），1例口服单药索非布韦的患者在疗程结束后HCV病毒载量仍高于正常值，后检查该患者病毒基因型为5型，经换用索非布韦+达卡他韦继续治疗12周后病毒载量转阴并获得SVR。6例患者治疗过程中全血细胞计数、血清转氨酶、肌酐及免疫抑制剂浓度水平均未见明显波动，不良反应为一过性皮疹（1例）及轻度眩晕（1例）。结论对于肾移植术后移植肾功能稳定的患者，服用DAAs治疗HCV安全有效，治疗药物首选索非布韦+达卡他韦联合用药。
- 直接抗病毒药物 /
- 肾移植 /
- 丙型病毒性肝炎 /
- 索非布韦 /
- 达卡他韦 /
- 雷迪帕韦 /
- 疗效 /
- 安全性
Abstract: Objective To observe the clinical efficacy and safety of direct-acting antiviral agents (DAAs) in the treatment of hepatitis C after renal transplantation. Methods Six patients were complicated with hepatitis C virus (HCV) at 8 to 43 months after renal transplantation with a median time of 19 months. Prior to treatment, the virus load was detected from 4.03×10³ to 8.18×10⁷ IU/mL. Four cases were administered with tacrolimus (FK506) + mycophenolate mofetil (MMF) + prednisone (Pred), and the remaining 2 received cyclosporin (CsA) + MMF + Pred. The serum creatinine level was lower than 200 μmol/L. The amount of urine and body weight remained stable. No severe mental irritation or trauma history was reported within 6 months before antiviral therapy. Six patients did not receive genotype test of HCV before DAAs therapy. Four patients were administered with sofosbuvir, 1 with sofosbuvir + ledipavir and 1 with sofosbuvir + daclatasvir for 12 weeks. The complete blood cell count, serum transaminase level, creatinine level and blood concentration of immunosuppressive agents were measured each week and serum HCV RNA level was quantitatively detected every 4 weeks. Results Among 6 patients, 5 were negative for HCV at 4 weeks after DAAs therapy and obtained sustained virological response (SVR) after DAAs treatment. One case administered with sofosbuvir alone was positive for HCV after DAAs therapy. The patient was infected with genotype 5 HCV. After 12-week administration of sofosbuvir + daclatasvir, the patient was negative for HCV and obtained SVR. No significant changes were observed in complete blood cell count, serum transaminase level, creatinine level and blood concentration of immunosuppressive agents. Adverse reactions included evanescent eruption in 1 case and mild dizziness in 1 case. Conclusions DAAs treatment is an effective and safe approach for patients with stable renal function after renal transplantation. Combined use of sofosbuvir+ daclatasvir is recommended as the optimal therapy.
- Uirect-acting antiviral agent /
- Renal transplantation /
- Hepatitis C /
- Sofosbuvir /
- Daclatasvir /
- Ledipavir /
- Efficacy /
- Safety

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图 1 6例患者治疗期间血清肌酐和免疫抑制剂血药浓度变化

Figure 1. Changes of serum creatinine and immunosuppressant blood concentration of 6 cases during treatment

下载: 全尺寸图片幻灯片

表 1 慢性丙型病毒肝炎抗病毒治疗病毒学应答指标的定义（部分）

Table 1. Viral response index of antiviral therapy for chronic hepatitis C (partial)

病毒学应答指标	定义
快速病毒学应答（RVR）	治疗第4周HCV RNA低于正常检测值下限（LLD）
完全早期病毒学应答（cEVR）	治疗第12周HCV RNA低于LLD
部分早期病毒学应答（pEVR）	治疗第12周HCV RNA较治疗前下降＞2 Log，但高于LLD
延迟病毒病毒学应答（DVR）	在pEVR的基础上，至第24周HCV RNA低于LLD
部分应答（PR）	在pEVR的基础上，至第24周HCV RNA仍高于LLD
无应答（NR）	治疗第12周HCV RNA较治疗前下降＜2 Log
突破（breakthrough）	在实现病毒学应答后，治疗过程中出现HCV RNA反弹
复发（relapse）	在实现病毒学应答后，治疗结束24周内HCV RNA可测
持续病毒学应答（SVR）	治疗结束后12及24周内HCV RNA均低于LLD，分别记为SVR12及SVR24
RVR: rapid virological response; cEVR: completely early virological response; pEVR: partial early virological response; DVR: delayed virological response; PR: partial response; NR: null response; SVR: sustained virological response; LLD: lower limit of detection

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表 2 6例肾移植术后丙型病毒性肝炎患者接受口服DAAs治疗情况及HCV RNA定量变化

Table 2. Treatment of oral DAAs and quantitative changes of HCV RNA on 6 cases with hepatitis C after renal transplantation

例次	性别	移植术后时间（月）	免疫抑制方案^a	DAAs 方案^b	HCV RNA定量(IU/mL)
例次	性别	移植术后时间（月）	免疫抑制方案^a	DAAs 方案^b	治疗前	治疗4周	治疗8周	治疗12周
1	男	22	F+M+P	S	3.65×10⁴	< 25	< 25	< 25
2	男	14	C+M+P	S	4.03×10³	< 25	< 25	< 25
3	男	19	F+M+P	S	7.25×10⁴	< 25	< 25	< 25
4	女	8	F+M+P	S	2.38×10⁶	4.55×10⁵	2.57×10³	1.02×10²
5	男	31	F+M+P	S+D	8.18×10⁷	< 25	< 25	< 25
6	男	43	C+M+P	S+L	3.58×10⁵	< 25	< 25	< 25
^a免疫抑制方案F+M+P为FK506+MMF+Pred，C+M+P为CsA+MMF+Pred；^bDAAs方案S为索非布韦，S+D为索非布韦+达卡他韦，S+L：索非布韦+雷迪帕韦

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