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直接作用抗病毒药物的全口服方案治疗慢性丙型肝炎合并晚期肝病的疗效:来自 HCV-TARGET 数据库的真实世界观察。

All-oral direct-acting antiviral therapy in HCV-advanced liver disease is effective in real-world practice: observations through HCV-TARGET database.

机构信息

Philadelphia, PA, USA.

New Haven, CT, USA.

出版信息

Aliment Pharmacol Ther. 2017 Jan;45(1):115-126. doi: 10.1111/apt.13823. Epub 2016 Oct 28.

DOI:10.1111/apt.13823
PMID:27790729
Abstract

BACKGROUND

Chronic hepatitis C virus therapy in patients with advanced liver disease remains a clinical challenge. HCV-TARGET collects data in patients treated at tertiary academic and community centres.

AIM

To assess efficacy of all-oral HCV therapy in advanced liver disease.

METHODS

Between December 2013 and October 2014, 240 patients with a MELD score of ≥10 initiated HCV treatment with an all-oral regimen. Data from the 220 patients who completed 12-week follow-up were analysed.

RESULTS

Genotype 1 (GT1) patients had higher sustained virological response (SVR) when treated with sofosbuvir plus simeprevir ± ribavirin than with sofosbuvir plus ribavirin (66-74% vs. 54%); GT1b vs GT1a (84% vs. 64%). SVR for GT2 was 72% with sofosbuvir plus ribavirin, while GT3 patients had a substantially lower response (35%). A decrease in MELD score was not clearly related to SVR over the short course of follow-up although some had improvements in MELD score, serum bilirubin and albumin. A predictor of virological response was albumin level while negative predictors were elevated bilirubin level and GT1a. Most patients with GT1 were treated with approximately 12-week duration of sofosbuvir and simeprevir ± ribavirin therapy while GT2 and GT3 patients were treated with approximately 12 and 24 weeks of sofosbuvir plus ribavirin respectively.

CONCLUSIONS

All-oral therapies are effective among patients with advanced liver disease with high levels of success in GT2 and GT1b, and may serve to reduce the severity of liver disease after SVR. Treatment for GT3 patients remains an unmet need. Clinical trial number: NCT01474811.

摘要

背景

慢性丙型肝炎病毒治疗在晚期肝病患者中仍然是一个临床挑战。HCV-TARGET 收集了在三级学术和社区中心接受治疗的患者的数据。

目的

评估全口服丙型肝炎病毒治疗在晚期肝病中的疗效。

方法

2013 年 12 月至 2014 年 10 月,240 名 MELD 评分≥10 的患者接受了全口服治疗方案的丙型肝炎病毒治疗。对完成 12 周随访的 220 名患者的数据进行了分析。

结果

与索非布韦加利巴韦林相比,索非布韦加西咪普韦±利巴韦林治疗基因型 1(GT1)患者的持续病毒学应答(SVR)更高(66-74% vs. 54%);GT1b 比 GT1a(84% vs. 64%)更高。GT2 患者接受索非布韦加利巴韦林治疗的 SVR 为 72%,而 GT3 患者的反应明显较低(35%)。在短期随访中,MELD 评分的下降与 SVR 无明显关系,尽管有些患者的 MELD 评分、血清胆红素和白蛋白有所改善。病毒学反应的预测因素是白蛋白水平,而负预测因素是胆红素水平升高和 GT1a。大多数 GT1 患者接受了大约 12 周的索非布韦和西咪普韦±利巴韦林治疗,而 GT2 和 GT3 患者分别接受了大约 12 周和 24 周的索非布韦加利巴韦林治疗。

结论

全口服治疗在晚期肝病患者中是有效的,GT2 和 GT1b 的成功率较高,并且可能有助于在 SVR 后降低肝病的严重程度。GT3 患者的治疗仍然是一个未满足的需求。临床试验编号:NCT01474811。

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