Cholongitas Evangelos, Pipili Chrysoula, Papatheodoridis George
Evangelos Cholongitas, 4 Department of Internal Medicine, Medical School of Aristotle University, Hippokration General Hospital of Thessaloniki, 54642 Thessaloniki, Greece.
World J Gastroenterol. 2015 Aug 28;21(32):9526-33. doi: 10.3748/wjg.v21.i32.9526.
The goal of therapy in chronic hepatitis C virus (HCV) infection is sustained virological response (SVR) which reflects HCV eradication. Treatment against HCV has dramatically improved with the recent availability of direct-acting antivirals (DAAs) including sofosbuvir, simeprevir, daclatasvir, ledipasvir/sofosbuvir, paritaprevir/ombitasvir and dasabuvir. Carefully selected combinations of these DAAs offer the potential for highly effective all-oral safe regimens even for patients with decompensated cirrhosis or liver transplant (LT) recipients. Like all current protease inhibitors, simeprevir and paritaprevir should not be used in patients with Child C cirrhosis, while sofosbuvir and ledipasvir/sofosbuvir should not be given in patients with severe renal impairment and glomerular filtration rate less than 30 mL/min. Drug-drug interactions may still occur with the current DAAs particularly in post-LT patients, in whom simeprevir should not be co-administered with cyclosporine and dose adjustments of calcineurin inhibitors are required in case of regimens including the ritonavir boosted paritaprevir. Phase II clinical trials and real life cohort studies have shown that sofosbuvir based combinations are safe and can achieve improvements of clinical status, high SVR rates and even prevention of post-LT HCV recurrence in patients with decompensated cirrhosis or LT-candidates. In the post-LT setting, sofosbuvir based regimens and the combination of paritaprevir/ombitasvir and dasabuvir have been reported to be safe and achieve high SVR rates, similar to those in non-transplant patients, being effective even in cases with cholestatic fibrosing hepatitis. Ongoing clinical trials and rapidly emerging real life data will further clarify the safety and efficacy of the new regimens in these settings.
慢性丙型肝炎病毒（HCV）感染的治疗目标是持续病毒学应答（SVR），这反映了HCV的根除。随着包括索磷布韦、simeprevir、达卡他韦、来迪帕司韦/索磷布韦、帕罗韦德/奥比他韦和达沙布韦在内的直接抗病毒药物（DAA）的近期问世，针对HCV的治疗有了显著改善。精心挑选的这些DAA组合为高效的全口服安全治疗方案提供了可能，即使对于失代偿期肝硬化患者或肝移植（LT）受者也是如此。与所有目前的蛋白酶抑制剂一样，simeprevir和帕罗韦德不应在Child C级肝硬化患者中使用，而索磷布韦和来迪帕司韦/索磷布韦不应给予严重肾功能损害且肾小球滤过率低于30 mL/min的患者。目前的DAA仍可能发生药物相互作用，尤其是在LT后患者中，其中simeprevir不应与环孢素联合使用，并且在包括利托那韦增强的帕罗韦德的治疗方案中，需要调整钙调神经磷酸酶抑制剂的剂量。II期临床试验和真实队列研究表明，基于索磷布韦的组合是安全的，并且可以改善临床状况、实现高SVR率，甚至预防失代偿期肝硬化患者或LT候选患者的LT后HCV复发。在LT后环境中，据报道基于索磷布韦的治疗方案以及帕罗韦德/奥比他韦和达沙布韦的组合是安全的，并能实现高SVR率，与非移植患者相似，即使在胆汁淤积性纤维化性肝炎病例中也有效。正在进行的临床试验和迅速出现的真实数据将进一步阐明这些治疗方案在这些情况下的安全性和有效性。
