NEJM：新联合用药方法治疗丙型肝炎

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一个大型的多中心临床试验已经发现一种抗病毒用药的联合治疗能够为90%多的晚期肝病患者根除C型肝炎感染。被称为ASTRAL-4试验的该项研究由BIDMC和山间医学中心的研究者们联合实施，并在线发表于11月17号的The New England Journal of Medicine 上。

“这项研究中超过一半的患者经历了一次失败的前期C性肝炎感染的治疗，”BIDMC肝脏病学与肝移植中心主任、哈佛医学院医学副教授即该研究的合作研究者Michael Curry说。“我们的试验显示使用常规抗病毒药Sofosbuvir和Velpatasvir联合，加或不加利巴韦林12周或24周治疗，都能成功治疗83%到94%的C型肝炎患者。”

C型肝炎病毒在全国范围内13亿到15亿人群中传染，是肝功能不全和肝硬化的一个普遍因素，它在健康肝脏受到损伤时开始发展起来，并最终使肝脏行使正常功能受阻。在美国47个不同地点总共有267名C型肝炎导致的肝功能不全患者参加了随机的3期临床试验。

“对现在伴有肝硬化和肝功能不全的患者，治疗C型肝炎感染的可行选择非常少，”Curry 说。“我们的研究发现在大批研究参与者中可以看得到早期肝功能的改善，这些结果主要通过蔡尔滋普得分（主要评价肝硬化严重程度）和MELD得分（主要用来确定病人进行肝移植的优势性）来指示的。”

肝脏是人体最大的实质性器官，发挥着多种作用，包括产生血蛋白类辅助凝血和免疫系统功能、产生胆汁用来消化食物以及供能葡萄糖的储存等。肝脏还可以去除身体有害物质如酒精。

“在接下来的10年里，因C型肝炎导致肝功能不全的病人数目有望显著增加，”Curry说。“这些新的发现暗示着患有更晚期肝病的患者依然能够从C型肝炎治疗中受益，并且这种感染的清除与肝功能的早期改善息息相关。”

来源：来宝网

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Sofosbuvir and Velpatasvir for HCV in Patients with Decompensated Cirrhosis.

Curry MP1, O'Leary JG, Bzowej N, Muir AJ, Korenblat KM, Fenkel JM, Reddy KR, Lawitz E, Flamm SL, Schiano T, Teperman L, Fontana R, Schiff E, Fried M, Doehle B, An D, McNally J, Osinusi A, Brainard DM, McHutchison JG, Brown RS Jr, Charlton M; ASTRAL-4 Investigators.

Background

As the population that is infected with the hepatitis C virus (HCV) ages, the number of patients with decompensated cirrhosis is expected to increase.

Methods

We conducted a phase 3, open-label study involving both previously treated and previously untreated patients infected with HCV genotypes 1 through 6 who had decompensated cirrhosis (classified as Child-Pugh-Turcotte class B). Patients were randomly assigned in a 1:1:1 ratio to receive the nucleotide polymerase inhibitor sofosbuvir and the NS5A inhibitor velpatasvir once daily for 12 weeks, sofosbuvir-velpatasvir plus ribavirin for 12 weeks, or sofosbuvir-velpatasvir for 24 weeks. The primary end point was a sustained virologic response at 12 weeks after the end of therapy.

Results

Of the 267 patients who received treatment, 78% had HCV genotype 1, 4% genotype 2, 15% genotype 3, 3% genotype 4, and less than 1% genotype 6; no patients had genotype 5. Overall rates of sustained virologic response were 83% (95% confidence interval [CI], 74 to 90) among patients who received 12 weeks of sofosbuvir-velpatasvir, 94% (95% CI, 87 to 98) among those who received 12 weeks of sofosbuvir-velpatasvir plus ribavirin, and 86% (95% CI, 77 to 92) among those who received 24 weeks of sofosbuvir-velpatasvir. Post hoc analysis did not detect any significant differences in rates of sustained virologic response among the three study groups. Serious adverse events occurred in 19% of patients who received 12 weeks of sofosbuvir-velpatasvir, 16% of those who received 12 weeks of sofosbuvir-velpatasvir plus ribavirin, and 18% of those who received 24 weeks of sofosbuvir-velpatasvir. The most common adverse events were fatigue (29%), nausea (23%), and headache (22%) in all patients and anemia (31%) in the patients receiving ribavirin.

Conclusions

Treatment with sofosbuvir-velpatasvir with or without ribavirin for 12 weeks and with sofosbuvir-velpatasvir for 24 weeks resulted in high rates of sustained virologic response in patients with HCV infection and decompensated cirrhosis.

http://www.nejm.org/doi/full/10.1056/NEJMoa1512614