Kwo Paul Y, Badshah Maaz B
aDepartment of Medicine, Division of Gastroenterology/Hepatology bDepartment of Medicine, Division of General Internal Medicine, Indiana University School of Medicine, Indianapolis, Indiana, USA.
Curr Opin Organ Transplant. 2015 Jun;20(3):235-41. doi: 10.1097/MOT.0000000000000198.
This article will review the new direct acting antiviral agent (DAA) drug classes for the treatment of hepatitis C, how they are combined and the relevant drug-drug interactions in the postliver transplant setting. Treatment options for chronic hepatitis C in patients with decompensated cirrhosis and end-stage renal disease will also be discussed.
The availability of new drug classes has increased the treatment options in patients with hepatitis C in the post-transplant settings. Clinical trials have concluded that sofosbuvir (SOF) with ledipasvir (LDV) may be safely administered with calcineurin inhibitors (tacrolimus, cyclosporine) and rapamycin inhibitors (sirolimus, everolimus). Similarly, paritaprevir/ritonavir, ombitasvir, and dasabuvir may be administered with tacrolimus and cyclosporine though appropriate dose adjustments must be made to the calcineurin inhibitors. In those with decompensated Childs B/C cirrhosis, SOF, SOF and LDV, as well as daclatasvir may be given without dose adjustment. In renal impairment, all DAAs may be used safely down to a glomerular filteration rate (GFR) of 30 ml/min. Simeprevir, paritaprevir, ombitasvir, and dasabuvir may be given for those down to GFR of 15 ml/min. Finally, daclatasvir may be given without dose administration change.
In summary, DAAs have better tolerability and greater efficacy than interferon-based therapy post-transplant. Drug-drug interactions must be carefully assessed when these newer agents are used for therapy in the postliver transplant settings. Thus far, dose adjustments for DAAs have not been required in chronic kidney disease though data are incomplete in those with severe chronic kidney disease (CKD) or on dialysis. Hepatitis C treatment in those with decompensated cirrhosis results in impaired hepatic metabolism that may affect DAA levels, and clinicians should carefully choose treatment options for Childs B and C cirrhotic patients.
本文将综述用于治疗丙型肝炎的新型直接作用抗病毒药物（DAA）类别、它们的联合使用方式以及肝移植后环境中的相关药物相互作用。还将讨论失代偿期肝硬化和终末期肾病患者慢性丙型肝炎的治疗选择。
新型药物类别的出现增加了移植后丙型肝炎患者的治疗选择。临床试验得出结论，索磷布韦（SOF）与雷迪帕韦（LDV）可与钙调神经磷酸酶抑制剂（他克莫司、环孢素）和雷帕霉素抑制剂（西罗莫司、依维莫司）安全联用。同样，帕利哌韦/利托那韦、奥比他韦和达沙布韦可与他克莫司和环孢素联用，不过必须对钙调神经磷酸酶抑制剂进行适当的剂量调整。在Childs B/C失代偿期肝硬化患者中，索磷布韦、索磷布韦与雷迪帕韦以及达拉他韦可无需调整剂量给药。在肾功能损害患者中，所有DAA药物在肾小球滤过率（GFR）低至30 ml/min时均可安全使用。对于GFR低至15 ml/min的患者，可给予simeprevir、帕利哌韦、奥比他韦和达沙布韦。最后，达拉他韦给药时无需改变剂量。
总之，DAA药物比移植后基于干扰素的疗法耐受性更好、疗效更佳。在肝移植后环境中使用这些新型药物进行治疗时，必须仔细评估药物相互作用。迄今为止，慢性肾病患者无需调整DAA药物剂量，不过重度慢性肾病（CKD）患者或接受透析患者的数据尚不完整。失代偿期肝硬化患者的丙型肝炎治疗会导致肝脏代谢受损，这可能会影响DAA药物水平，临床医生应为Childs B级和C级肝硬化患者谨慎选择治疗方案。
