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

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.

Keywords: Hepatic fibrosis; Liver injury; Liver microenvironment; Sorafenib; Therapeutic drug.