核苷酸聚合酶抑制剂Sofosbuvir联合利巴韦林治疗丙型肝炎

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作者 ： Edward J Gane ,Catherine A Stedman ,Robert H Hyland ,Xiao Ding ,Evguenia Svarovskaia ,William T Symonds
期刊名称：新英格兰医学杂志(NEJM)
发表时间：2013-01-03
索引：N. Engl. J. Med..2013 Jan 3;368(1):34-44.

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背景
丙肝病毒（HCV）感染的标准治疗方法是干扰素，通过皮下注射给药，并且导致棘手的副作用。我们评价了一种口服的丙型肝炎病毒核苷酸聚合酶抑制剂sofosbuvir在干扰素减量和无干扰素条件下对HCV感染的治疗效果。

方法
我们对8组患者进行开放标签治疗，将40例初治的基因2型或3型HCV感染患者随机分为4组，每组均接受sofosbuvir（剂量400mg，每日一次）联合利巴韦林的治疗12周。其中3组同时接受聚乙二醇干扰素α-2a治疗4、8或12周。另外2组感染基因2型或3型HCV的初治患者接受sofosbuvir单药治疗12周或sofosbuvir联合聚乙二醇干扰素α-2a和利巴韦林治疗8周。2组感染基因1型HCV的患者接受sofosbuvir和利巴韦林治疗12周，其中10名患者对之前的治疗无应答， 25名患者未经治疗。我们报告了治疗结束后24周的持续病毒学应答率。

结果
随机分组的40例患者在治疗后24周均有持续病毒学应答，包括接受sofosbuvir联合利巴韦林治疗12周且未使用干扰素的10名（100％）患者，以及接受sofosbuvir联合利巴韦林治疗12周和干扰素治疗4、8或12周的30名（100％）患者。其他感染基因2或3型HCV的患者中，所有接受sofosbuvir联合聚乙二醇干扰素α-2a和利巴韦林治疗8周的10名（100%）患者在治疗后24周均有持续病毒学应答，而接受sofosbuvir单药治疗的患者中有6名（60%）有持续病毒学应答。25名初治基因1型HCV感染患者中，21名（84％）在治疗后24周有持续病毒学应答， 而10名之前治疗无应答的患者中只有1名（10％）有持续病毒学应答。最常见的不良反应为头痛、疲劳、失眠、恶心、皮疹、贫血。

结论
Sofosbuvir联合利巴韦林治疗12周对于初治基因1、2或3型HCV感染患者可能是有效的。

北京大学 陶辉翻译 北京协和医学院 董润审核

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Background
The standard treatment for hepatitis C virus (HCV) infection is interferon, which is administered subcutaneously and can have troublesome side effects. We evaluated sofosbuvir, an oral nucleotide inhibitor of HCV polymerase, in interferon-sparing and interferon-free regimens for the treatment of HCV infection.

Methods
We provided open-label treatment to eight groups of patients. A total of 40 previously untreated patients with HCV genotype 2 or 3 infection were randomly assigned to four groups; all four groups received sofosbuvir (at a dose of 400 mg once daily) plus ribavirin for 12 weeks. Three of these groups also received peginterferon alfa-2a for 4, 8, or 12 weeks.

Two additional groups of previously untreated patients with HCV genotype 2 or 3 infection received sofosbuvir monotherapy for 12 weeks or sofosbuvir plus peginterferon alfa-2a and ribavirin for 8 weeks. Two groups of patients with HCV genotype 1 infection received sofosbuvir and ribavirin for 12 weeks: 10 patients with no response to prior treatment and 25 with no previous treatment.

We report the rate of sustained virologic response 24 weeks after therapy.

Results
Of the 40 patients who underwent randomization, all 10 (100%) who received sofosbuvir plus ribavirin without interferon and all 30 (100%) who received sofosbuvir plus ribavirin for 12 weeks and interferon for 4, 8, or 12 weeks had a sustained virologic response at 24 weeks.

For the other patients with HCV genotype 2 or 3 infection, all 10 (100%) who received sofosbuvir plus peginterferon alfa-2a and ribavirin for 8 weeks had a sustained virologic response at 24 weeks, as did 6 of 10 (60%) who received sofosbuvir monotherapy.

Among patients with HCV genotype 1 infection, 21 of 25 previously untreated patients (84%) and 1 of 10 with no response to previous therapy (10%) had a sustained virologic response at 24 weeks. The most common adverse events were headache, fatigue, insomnia, nausea, rash, and anemia.

Conclusions
Sofosbuvir plus ribavirin for 12 weeks may be effective in previously untreated patients with HCV genotype 1, 2, or 3 infection.