Future therapy of hepatitis C
Future therapy of hepatitis C
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DOI：
10.1053/jhep.2002.36795
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发表时间：
2002-11-01
期刊：
影响因子：
13.5
通讯作者：
Patel, K
中科院分区：
文献类型：
--
作者：
McHutchison, JG;Patel, K
目前可用于治疗慢性丙型肝炎的疗法对一半患者有效，但价格昂贵，通常耐受性差，不适合某些患者人群。理想的治疗应该是高效的、口服生物可利用的、副作用最小的、成本有效的，并且适合大多数丙型肝炎患者。丙型肝炎病毒（HCV）的复制周期和病毒多聚蛋白组分的结构和晶体学定义的最新进展改善了开发新疗法的前景。缺乏HCV感染的小动物模型继续阻碍新的抗病毒药物和疫苗的临床前评价的进展。增强对当前疗法的反应的策略包括开发新型干扰素和递送系统、与利巴韦林相比具有减少的溶血的核苷类似物、肌苷5'单磷酸脱氢酶抑制剂和正在被评估为对基于干扰素的方案的连续疗法的其他免疫调节剂。临床前或早期人体试验中的化合物包括抑制病毒特异性酶（如丝氨酸蛋白酶、RNA聚合酶和解旋酶）的小分子，或阻止翻译起始的那些（如反义分子和核酶）。抗纤维化药物也正在开发中，试图防止疾病进展的患者中，HCV RNA不能根除。虽然这些新化合物的出现代表了HCV治疗的一个令人兴奋的阶段，但它们的安全性和有效性需要确定。这些新疗法中的大多数不太可能在未来3至5年内用于常规临床使用。
Currently available therapies for the treatment of chronic hepatitis C are effective in half of patients, but are expensive, often poorly tolerated, and unsuitable for certain patient populations. The ideal therapy would be highly effective, orally bioavailable, have minimal side effects, be cost effective, and suitable for the majority of patients with hepatitis C. Recent advances in understanding the replication cycle of hepatitis C virus (HCV) and structural, crystallographic definitions of components of the viral polyprotein have improved the prospects for development of novel therapies. The lack of a small animal model of HCV infection continues to hamper progress in the preclinical evaluation of new antivirals and vaccines. Strategies to enhance response to current therapies include the development of novel interferons and delivery systems, nucleoside analogues that have reduced hemolysis compared with ribavirin, inosine 5' monophosphate dehydrogenase inhibitors, and other immunomodulators that are being evaluated as adjunctive therapy to interferon-based regimens. Compounds in preclinical or early phase human trials include small molecules that inhibit virus specific enzymes (such as the serine proteases, RNA polymerase and helicase), or those that prevent translation initiation (such as antisense molecules and ribozymes). Antifibrotic agents are also being developed in an attempt to prevent disease progression in patients in whom HCV RNA cannot be eradicated. While the advent of these newer compounds represent an exciting phase in the treatment of HCV, their safety and efficacy need to be established. Most of these newer therapies are unlikely to be available for routine clinical use in the next 3 to 5 years.