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索磷布韦和达拉他韦联合治疗肝移植后严重复发性胆汁淤积性丙型肝炎。

Sofosbuvir and daclatasvir combination therapy in a liver transplant recipient with severe recurrent cholestatic hepatitis C.

机构信息

Department of Internal Medicine, University of Michigan Medical Center, Princeton, NJ, USA.

出版信息

Am J Transplant. 2013 Jun;13(6):1601-5. doi: 10.1111/ajt.12209. Epub 2013 Apr 17.

Abstract

Recurrent HCV infection following liver transplantation can lead to accelerated allograft injury that is difficult to treat with interferon. The aim of this study is to describe the first ever use of an interferon-free, all oral regimen in a liver transplant recipient with severe recurrent HCV. A 54-year-old male with HCV genotype 1b developed severe cholestatic HCV at 6 months posttransplant with ascites, AST 503 IU/mL, alkaline phosphatase of 298 IU/mL, HCV RNA of 12 000 000 IU/mL, and histological cholestasis with pericellular fibrosis. Sofosbuvir, an HCV polymerase inhibitor (400 mg/day), and daclatasvir, an HCV NS5A replication complex inhibitor (60 mg/day), were co-administered for 24 weeks. Within 4 weeks of initiating treatment, serum HCV RNA levels became undetectable and liver biochemistries normalized with concomitant resolution of ascites. The patient achieved a sustained virological response with undetectable HCV RNA at 9 months posttreatment. During and following treatment, the daily dose and blood level of tacrolimus remained stable and unchanged. The rapid and sustained suppression of HCV replication in this liver transplant recipient provides great promise for the use of combination oral antiviral regimens in other immunosuppressed and interferon refractory HCV patients.

摘要

肝移植后 HCV 的反复感染可导致移植物加速损伤,这很难用干扰素治疗。本研究旨在描述首例在肝移植受者中使用无干扰素、全口服方案治疗严重复发性 HCV 的病例。一名 54 岁男性,HCV 基因型 1b,移植后 6 个月发生严重胆汁淤积性 HCV,伴有腹水、AST 503IU/mL、碱性磷酸酶 298IU/mL、HCV RNA 为 1200 万 IU/mL,组织学表现为胆汁淤积伴细胞周纤维化。给予索磷布韦(HCV 聚合酶抑制剂,400mg/天)和达卡他韦(HCV NS5A 复制复合物抑制剂,60mg/天)联合治疗 24 周。治疗开始后 4 周内,血清 HCV RNA 水平降至不可检测,肝生化指标恢复正常,腹水消退。治疗 9 个月后患者获得持续病毒学应答,HCV RNA 不可检测。在治疗期间和治疗后,他克莫司的日剂量和血药浓度保持稳定且不变。该肝移植受者中 HCV 复制的快速和持续抑制为其他免疫抑制和干扰素难治性 HCV 患者使用联合口服抗病毒方案提供了很大希望。

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