Sofosbuvir: A novel treatment option for chronic hepatitis C infection.
Sofosbuvir: A novel treatment option for chronic hepatitis C infection.
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DOI：
10.4103/0976-500x.142464
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发表时间：
2014-10
影响因子：
0.2
通讯作者：
Natt NK
中科院分区：
文献类型：
--
作者：
Bhatia HK;Singh H;Grewal N;Natt NK
丙型肝炎目前感染了全世界超过1.7亿人，导致显著的发病率和死亡率。目前HCV感染的标准治疗，包括两种蛋白酶抑制剂之一特拉匹韦或博赛匹韦，治疗12-32周，与聚乙二醇化干扰素α-2 α（PEG-IFN-α）和利巴韦林一起沿着长达48周，在许多情况下是不令人满意的，因为缺乏疗效或因为治疗相关的不良反应。迫切需要具有改善的功效以及安全性的新药。Sofosbuvir是一种最近批准的核苷酸类似物，是丙型肝炎病毒（HCV）中NS 5 B聚合酶的高效抑制剂，与其他几种药物联合使用（含或不含PEG-INF）对HCV具有高疗效。它提供了许多优点，由于其高效力，低副作用，口服给药，和高屏障的阻力。在许多大型和精心设计的2期和3期临床试验中证明了疗效和安全性，如NEUTRINO、PROTON、ELECTRON、ATOMIC、COSMOS、FUSION、FISION、NUCLEAR、POSITRON等。它通常是很好的耐受性。发生的不良事件包括：头痛、失眠、疲劳、恶心、头晕、鼻炎、上呼吸道感染、皮疹、背痛、1级贫血和4级淋巴细胞减少症;然而，只有当这种药物实际大规模使用时，才能判断确切的安全性。
Hepatitis C currently infects more than 170 million people around the world, leading to significant morbidity and mortality. The current standard of care for HCV infection, including one of the two protease inhibitors, telaprevir or boceprevir, for 12-32 weeks, along with pegylated interferon alfa-2a (PEG-IFN-α) and ribavirin for up to 48 weeks, is unsatisfactory in many cases, either because of lack of efficacy or because of treatment-related adverse effects. There is an urgent need of new drugs with improved efficacy as well as a safety profile. Sofosbuvir, a recently approved nucleotide analog, is a highly potent inhibitor of the NS5B polymerase in the Hepatitis C virus (HCV), and has shown high efficacy in combination with several other drugs, with and without PEG-INF, against HCV. It offers many advantages due to its high potency, low side effects, oral administration, and high barrier to resistance. The efficacy and safety were demonstrated in many large and well-designed phase 2 and phase 3 clinical trials like NEUTRINO, PROTON, ELECTRON, ATOMIC, COSMOS, FUSION, FISSION, NUCLEAR, POSITRON, and the like. It is generally well-tolerated. Adverse events that occurred include: Headache, insomnia, fatigue, nausea, dizziness, pruritis, upper respiratory tract infections, rash, back pain, grade 1 anemia, and grade 4 lymphopenia; however, the exact safety profile can only be judged when this drug is actually used on a large scale.