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基于索磷布韦治疗丙型肝炎病毒3型慢性感染——一项斯堪的纳维亚地区的真实世界研究

Sofosbuvir based treatment of chronic hepatitis C genotype 3 infections-A Scandinavian real-life study.

作者信息

Dalgard Olav, Weiland Ola, Noraberg Geir, Karlsen Lars, Heggelund Lars, Färkkilâ Martti, Balslev Ulla, Belard Erika, Øvrehus Anne, Skalshøi Kjær Mette, Krarup Henrik, Thorup Røge Birgit, Hallager Sofie, Madsen Lone G, Lund Laursen Alex, Lagging Martin, Weis Nina

机构信息

Akershus University Hospital, Lørenskog, Norway.

Institute of Clinical Medicine, University of Oslo, Oslo, Norway.

出版信息

PLoS One. 2017 Jul 13;12(7):e0179764. doi: 10.1371/journal.pone.0179764. eCollection 2017.

Abstract

BACKGROUND AND AIMS

Chronic hepatitis C virus (HCV) genotype 3 infection with advanced liver disease has emerged as the most challenging to treat. We retrospectively assessed the treatment outcome of sofosbuvir (SOF) based regimes for treatment of HCV genotype 3 infections in a real life setting in Scandinavia.

METHODS

Consecutive patients with chronic HCV genotype 3 infection were enrolled at 16 treatment centers in Denmark, Sweden, Norway and Finland. Patients who had received a SOF containing regimen were included. The fibrosis stage was evaluated by liver biopsy or transient liver elastography. The following treatments were given according availability and local guidelines: 1) SOF + ribavirin (RBV) for 24 weeks, 2) SOF + daclatasvir (DCV) +/-RBV for 12-24 weeks, 3) SOF + pegylated interferon alpha (peg-IFN-α) + RBV for 12 weeks or 4) SOF/ledipasvir (LDV) + RBV for 12-16 weeks. The primary endpoint was sustained virological response (SVR) assessed at week 12 (SVR12) after end of treatment.

RESULTS

We included 316 patients with a mean age of 55 years (range 24-79), 70% men, 49% treatment experienced, 58% with compensated cirrhosis and 12% with decompensated cirrhosis.In the modified intention to treat (mITT) population SVR12 was achieved in 284/311 (91%) patients. Among 26 treatment failures, five had non-response, 3 breakthrough and 18 relapse. Five patients were not included in the mITT population. Three patients died from reasons unrelated to treatment and two were lost to follow-up. The SVR12 rate was similar for all treatment regimens, but lower in men (p = 0.042), and in patients with decompensated liver disease (p = 0.004).

CONCLUSION

We found that sofosbuvir based treatment in a real-life setting could offer SVR rates exceeding 90% in patients with HCV genotype 3 infection and advanced liver disease.

摘要

背景与目的

慢性丙型肝炎病毒(HCV)3型感染合并晚期肝病已成为最难治疗的情况。我们回顾性评估了在斯堪的纳维亚半岛现实生活环境中基于索磷布韦(SOF)的治疗方案对HCV 3型感染的治疗效果。

方法

在丹麦、瑞典、挪威和芬兰的16个治疗中心连续纳入慢性HCV 3型感染患者。纳入接受过含SOF方案治疗的患者。通过肝活检或瞬时弹性成像评估纤维化阶段。根据药物可及性和当地指南给予以下治疗:1)SOF + 利巴韦林(RBV)治疗24周,2)SOF + 达卡他韦(DCV)+/- RBV治疗12 - 24周,3)SOF + 聚乙二醇化干扰素α(peg - IFN -α)+ RBV治疗12周,或4)SOF/来迪派韦(LDV)+ RBV治疗12 - 16周。主要终点是治疗结束后第12周评估的持续病毒学应答(SVR)(SVR12)。

结果

我们纳入了316例患者,平均年龄55岁(范围24 - 79岁),70%为男性,49%有治疗史,58%为代偿期肝硬化,12%为失代偿期肝硬化。在改良意向性治疗(mITT)人群中,284/311(91%)例患者实现了SVR12。在26例治疗失败患者中,5例无应答,3例出现突破,18例复发。5例患者未纳入mITT人群。3例患者因与治疗无关的原因死亡,2例失访。所有治疗方案的SVR12率相似,但男性患者(p = 0.042)和失代偿期肝病患者(p = 0.004)的SVR12率较低。

结论

我们发现,在现实生活环境中,基于索磷布韦的治疗可为HCV 3型感染合并晚期肝病患者提供超过90%的SVR率。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/547c/5509146/cbc9f7e30cfa/pone.0179764.g001.jpg

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