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

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

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4.03×10~3~8.18×10~7 IU/m L,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(Cs A)+MMF+Pred(2例),治疗前血清肌酐水平低于200μmol/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。

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 ×10^3 to 8.18 ×10^7 IU/mL. Four cases were administered with tacrolimus （ FKS06 ） ＋ 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, I with sofosbuvir ＋ ledipavir and I 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.