Division of Gastroenterology/Hepatology, Duke Clinical Research Institute, Duke University, Durham, NC 27715, USA.
Aliment Pharmacol Ther. 2009 Apr 1;29(7):689-705. doi: 10.1111/j.1365-2036.2009.03927.x. Epub 2009 Jan 17.
The need for effective treatment for chronic hepatitis C infection has driven the development of novel antiviral agents that target specific steps in the viral replication cycle.
To evaluate the current literature concerning investigational agents for chronic hepatitis C virus infection.
Resources used included PubMed, conference proceedings from the American and European Liver Associations' meetings 2005-2008 and the National Institute of Health's clinical trials website (http://www.clinicaltrials.gov). The focus was restricted to investigational agents that have progressed beyond preclinical development.
Over 50 investigational agents for chronic hepatitis C infection are currently in clinical development. Specifically targeted anti-viral therapy for HCV (STAT-C) shows great promise with NS3/4a protease inhibitors now entering phase 3 programmes. New interferon-alpha and ribavirin formulations aim to optimize anti-viral efficacy yet limit toxicity. Other candidates include novel immunomodulators and therapeutic vaccines.
A new era of therapy for chronic hepatitis C beckons, promising increased cure rates with shortened duration of therapy. However, the era will not be without challenges including viral resistance, drug toxicity and the need to optimize combination therapy in the face of a rapidly evolving therapeutic arsenal.
慢性丙型肝炎感染的有效治疗需求推动了针对病毒复制周期特定步骤的新型抗病毒药物的发展。
评估慢性丙型肝炎病毒感染的研究药物的现有文献。
使用的资源包括 PubMed、2005-2008 年美国和欧洲肝脏协会会议的会议记录以及美国国立卫生研究院的临床试验网站(http://www.clinicaltrials.gov)。重点仅限于已超越临床前开发的研究药物。
目前有超过 50 种治疗慢性丙型肝炎感染的研究药物正在临床开发中。针对 HCV 的特异性抗病毒治疗(STAT-C)显示出巨大的前景,NS3/4a 蛋白酶抑制剂现已进入 3 期计划。新的干扰素-α和利巴韦林制剂旨在优化抗病毒疗效,同时限制毒性。其他候选药物包括新型免疫调节剂和治疗性疫苗。
慢性丙型肝炎治疗的新时代即将到来,有望提高治愈率,缩短治疗时间。然而,这一时代并非没有挑战,包括病毒耐药性、药物毒性以及在面对快速发展的治疗武器库时需要优化联合治疗。