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索拉非尼:一种治疗肝纤维化及其结局的潜在治疗药物。

Sorafenib: A potential therapeutic drug for hepatic fibrosis and its outcomes.

机构信息

Department of Surgery, Zhejiang University Hospital, Zhejiang University, Hangzhou, Zhejiang 310027, China.

Department of General Surgery, Sir Run Run Shaw Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang 310016, China.

出版信息

Biomed Pharmacother. 2017 Apr;88:459-468. doi: 10.1016/j.biopha.2017.01.107. Epub 2017 Jan 22.

Abstract

Hepatic fibrosis is a common response to liver injury that occurs in almost all liver diseases and is characterized by an excessive deposition of extracellular matrix, which can cause hepatic dysfunction and develop into cirrhosis. There is no curative treatment except liver transplantation and few treatments have been thoroughly validated in the clinic or commercialized as a therapy. Recently, sorafenib, an FDA approved molecular targeted drug for the treatment of advanced hepatocellular and renal cell carcinomas, has been reported to exert anti-fibrotic effects in liver fibrosis. Animal models showed that sorafenib ameliorated intrahepatic vascular resistance, reduced portal hypertension, and reduced intrahepatic fibrosis, inflammation and angiogenesis. In this review, we highlight the potential molecular, cellular, microenvironmental mechanisms underlying the antifibrotic effects of sorafenib in fibrotic liver disease, and briefly discuss the potential of sorafenib for hepatic fibrogenesis and major complications in clinical treatments. There is a long way to go before sorafenib can be applied in preclinical practice and clinical therapy of liver fibrosis. Further studies are required to clarify its anti-fibrotic role, effective dose, and side effects.

摘要

肝纤维化是一种常见的肝脏损伤反应,几乎发生在所有肝脏疾病中,其特征是细胞外基质的过度沉积,可导致肝功能障碍并发展为肝硬化。除肝移植外,尚无治愈方法,临床上很少有治疗方法得到彻底验证或商业化作为治疗方法。最近,索拉非尼是一种获得 FDA 批准的用于治疗晚期肝细胞癌和肾细胞癌的分子靶向药物,据报道其在肝纤维化中具有抗纤维化作用。动物模型表明,索拉非尼可改善肝内血管阻力,降低门静脉高压,并减少肝内纤维化、炎症和血管生成。在这篇综述中,我们强调了索拉非尼在纤维化性肝病中的抗纤维化作用的潜在分子、细胞和微环境机制,并简要讨论了索拉非尼在临床治疗肝纤维化和主要并发症中的应用潜力。在索拉非尼能够应用于肝纤维化的临床前实践和临床治疗之前,还有很长的路要走。需要进一步的研究来阐明其抗纤维化作用、有效剂量和副作用。

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