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当前和未来的 HCV 治疗:我们还需要其他抗 HCV 药物吗?

Current and future HCV therapy: do we still need other anti-HCV drugs?

机构信息

Sezione di Gastroenterologia e Epatologia, Di.Bi.M.I.S., University of Palermo, Palermo, Italy.

出版信息

Liver Int. 2015 Jan;35 Suppl 1:4-10. doi: 10.1111/liv.12714.

Abstract

Eradication of hepatitis C virus (HCV) infection, at least in compensated patients, can help improve the outcomes of liver disease such as cirrhosis, hepatocellular carcinoma (HCC) and liver transplantation, as well as perhaps extra-hepatic complications such as diabetes and cardiovascular risk. In the past few years, the landscape of antiviral therapy has evolved at a breathtaking pace from pegylated interferon (PEG-IFN) plus ribavirin (RBV) (PEG-IFN/RBV) to IFN-based strategies combining direct acting antivirals (DDAs) with PEG-IFN/RBV and finally IFN-free combinations of DAAs. In particular with these most recent developments, treatment regimens have become shorter, safer and even more effective, with a wide range of indications. Nevertheless, research continues and newer antiviral drugs are still under development. At a point when a >90% sustained virological response (SVR) is being claimed with all new available regimens, pharmacological and clinical research should be addressing unresolved areas, such as cases of suboptimal SVR or to increase effectiveness rather than pursuing the development of new 'me-too' drugs. The issues which should be given priority for further development include the following: Improving the results of IFN-free regimens in patients with genotype 3 (HCV-3) infection. Identifying the indications for the treatment in patients with compensated and decompensated cirrhosis. Identifying standardized or personalized backup strategies in patients who do not respond to IFN-free regimens. Finally, because of financial constraints, the high cost of IFN-free strategies prevents their universal use in CHC patients and coverage by national healthcare systems. Thus, efforts must be made to document cost-effectiveness in all clinical scenarios and to develop more affordable IFN-free regimens.

摘要

清除丙型肝炎病毒 (HCV) 感染,至少在代偿期患者中,可以帮助改善肝脏疾病的结局,如肝硬化、肝细胞癌 (HCC) 和肝移植,以及可能的肝外并发症,如糖尿病和心血管风险。在过去几年中,抗病毒治疗的格局以惊人的速度从聚乙二醇干扰素 (PEG-IFN) 加利巴韦林 (RBV) (PEG-IFN/RBV) 发展到基于 IFN 的联合直接作用抗病毒药物 (DDAs) 的策略,再到无 IFN 的 DDA 联合治疗。特别是随着这些最新进展,治疗方案变得更短、更安全,甚至更有效,适应证范围更广。然而,研究仍在继续,新的抗病毒药物仍在开发中。当所有新的可用方案都能达到>90%的持续病毒学应答 (SVR) 时,药理学和临床研究应该解决未解决的问题,例如 SVR 不理想的情况,或者提高疗效,而不是追求开发新的“me-too”药物。应该优先进一步开发的问题包括:

  • 提高无 IFN 方案在 HCV-3 感染患者中的疗效。

  • 确定代偿期和失代偿期肝硬化患者的治疗适应证。

  • 确定对无 IFN 方案无应答的患者的标准化或个体化备用策略。

  • 最后,由于财政限制,无 IFN 策略的高昂成本阻止了其在 CHC 患者中的普遍应用和国家卫生保健系统的覆盖。因此,必须努力在所有临床情况下证明成本效益,并开发更负担得起的无 IFN 方案。

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