Kawaoka T, Imamura M, Kan H, Fujino H, Fukuhara T, Kobayashi T, Honda Y, Naeshiro N, Hiramatsu A, Tsuge M, Hayes C N, Kawakami Y, Aikata H, Ochi H, Ishiyama K, Tashiro H, Ohdan H, Chayama K
Department of Gastroenterology and Metabolism, Hiroshima University Hospital, Hiroshima, Japan.
Division of Frontier Medical Science, Department of Surgery, Programs for Biomedical Research, Graduate School of Biomedical Science, Hiroshima University, Hiroshima, Japan.
Transplant Proc. 2015 Apr;47(3):809-14. doi: 10.1016/j.transproceed.2014.10.052.
We previously reported our data on telaprevir (TVR) used in combination with pegylated-interferon and ribavirin (PEG-IFN/RBV) for the treatment of recurrent hepatitis C virus (HCV) genotype 1 infection after liver transplantation (LT). TVR substantially increases the blood levels of immunosuppressive agents such as cyclosporine and tacrolimus for drug-drug interactions. On the other hand, the effect of simeprevir (SMV) on the blood levels of these immunosuppressive agents is unclear. We report 2 patients who achieved viral responses with little effect on the blood levels of cyclosporine and tacrolimus using SMV plus PEG-IFN/RBV treatment. The first was a 71-year-old woman with HCV-related liver cirrhosis and hepatocellular carcinoma who failed to respond to PEG-IFN/RBV after living donor LT. She was treated with 40 mg/d of cyclosporine, and received SMV plus PEG-IFN/RBV treatment. The second was a 65-year-old man with HCV-related liver cirrhosis who failed to respond to PEG-IFN/RBV after living donor LT. He was treated with 3 mg/d of tacrolimus, and received SMV plus PEG-IFN/RBV treatment. Serum HCV RNA became undetectable using TaqMan polymerase chain reaction (PCR) test after 4 weeks of treatment in both patients, and no remarkable fluctuation in blood concentration was observed either in cyclosporine or tacrolimus during the 12 weeks of SMV treatment. Completion of 12-week SMV triple therapy was followed by PEG-IFNα2b plus RBV, and both patients achieved sustained virological response 12 weeks after the end of treatment. SMV plus PEG-IFNRBV treatment showed a remarkable viral response with little effect on blood levels of immunosuppressive agents for recurrent HCV genotype 1 infection after LT.
我们之前报告了关于特拉匹韦（TVR）联合聚乙二醇干扰素和利巴韦林（PEG-IFN/RBV）用于治疗肝移植（LT）后复发性丙型肝炎病毒（HCV）1型感染的数据。由于药物相互作用，TVR会大幅提高环孢素和他克莫司等免疫抑制剂的血药浓度。另一方面，simeprevir（SMV）对这些免疫抑制剂血药浓度的影响尚不清楚。我们报告了2例使用SMV加PEG-IFN/RBV治疗后实现病毒学应答且对环孢素和他克莫司血药浓度影响较小的患者。第一例是一名71岁患有HCV相关肝硬化和肝细胞癌的女性，活体供肝LT后对PEG-IFN/RBV无应答。她接受40mg/d的环孢素治疗，并接受SMV加PEG-IFN/RBV治疗。第二例是一名65岁患有HCV相关肝硬化的男性，活体供肝LT后对PEG-IFN/RBV无应答。他接受3mg/d的他克莫司治疗，并接受SMV加PEG-IFN/RBV治疗。两名患者治疗4周后，使用TaqMan聚合酶链反应（PCR）检测血清HCV RNA均不可测，且在SMV治疗的12周内，环孢素或他克莫司的血药浓度均未观察到明显波动。完成12周的SMV三联疗法后给予PEG-IFNα2b加RBV，两名患者在治疗结束后12周均实现了持续病毒学应答。对于LT后复发性HCV 1型感染，SMV加PEG-IFN/RBV治疗显示出显著的病毒学应答，且对免疫抑制剂血药浓度影响较小。
