Department of Gastroenterology, Alfred Hospital, Commercial Rd, Melbourne, VIC, 3004, Australia.
Drugs. 2015 May;75(8):823-34. doi: 10.1007/s40265-015-0401-2.
Chronic hepatitis C virus (HCV) infection is a major global health concern, resulting in significant morbidity and mortality. Treatment using interferon-based therapy in patients with HCV-related cirrhosis has been problematic due to toxicity and poor tolerability. Furthermore, interferon therapy is contraindicated in those with advanced cirrhosis or clinical decompensation, who are arguably the group most in need of viral eradication. The arrival of the direct-acting antiviral (DAA) era has resulted in the development of well-tolerated and highly effective interferon-free drug regimens that promise to dramatically change the therapeutic landscape for those with advanced HCV-related liver disease, including patients with clinical decompensation or pre-liver transplantation. Many successful DAA combinations have emerged; however, a number of challenges remain including the establishment of the optimal treatment duration, the ideal combination of drug classes and determining the role of ribavirin. Moreover, the identification of treatment-experienced patients with genotype 3 HCV cirrhosis as a difficult-to-treat subgroup is a significant impediment to overcome, as are those who have failed prior DAA therapy. Despite these barriers, the ongoing prolific development of safe and effective DAA combinations indicates the future is optimistic for the ultimate goal of HCV eradication.
慢性丙型肝炎病毒 (HCV) 感染是一个重大的全球健康问题，导致了大量的发病率和死亡率。由于毒性和较差的耐受性，在丙型肝炎相关肝硬化患者中使用基于干扰素的治疗一直存在问题。此外，干扰素治疗在晚期肝硬化或临床失代偿患者中是禁忌的，这些患者可以说是最需要病毒清除的人群。直接作用抗病毒 (DAA) 时代的到来带来了耐受性良好且高效的无干扰素药物方案，有望为患有晚期丙型肝炎相关肝病的患者（包括临床失代偿或肝移植前患者）带来显著改变治疗前景。许多成功的 DAA 组合已经出现；然而，仍存在许多挑战，包括确定最佳治疗持续时间、药物类别理想组合以及确定利巴韦林的作用。此外，识别基因型 3 丙型肝炎肝硬化的治疗经验丰富患者作为一个难以治疗的亚组是一个重大障碍，对于那些已经失败的 DAA 治疗患者也是如此。尽管存在这些障碍，但安全有效的 DAA 组合的持续大量开发表明，丙型肝炎病毒清除的最终目标是乐观的。
