Fibroblast growth factor signaling in non-alcoholic fatty liver disease and non-alcoholic steatohepatitis: Paving the way to hepatocellular carcinoma

Abstract

Metabolic disorders are increasingly leading to non-alcoholic fatty liver disease, subsequent steatohepatitis, cirrhosis and hepatocellular carcinoma. Fibroblast growth factors and their receptors play an important role in maintaining metabolic homeostasis also in the liver and disorders in signaling have been identified to contribute to those pathophysiologic conditions leading to hepatic lipid accumulation and chronic inflammation. While specific and well tolerated inhibitors of fibroblast growth factor receptor activity are currently developed for (non-liver) cancer therapy, treatment of non-alcoholic fatty liver disease and non-alcoholic steatohepatitis is still limited. Fibroblast growth factor-mimicking or restoring approaches have recently evolved as a novel therapeutic option and the impact of such interactions with the fibroblast growth factor receptor signaling network during non-alcoholic fatty liver disease/non-alcoholic steatohepatitis development is reviewed here.

Keywords: Fibroblast growth factor; Fibroblast growth factor receptor; Non-alcoholic fatty liver disease; Non-alcoholic steatohepatitis; Fibrosis; Cirrhosis; Hepatocellular carcinoma

Core tip: Non-alcoholic fatty liver disease and non-alcoholic steatohepatitis show globally rising incidences and are expected to become the main reason for liver fibrosis, cirrhosis, liver cancer and end-stage liver disease with need for transplantation. Liver metabolism is, among other factors, regulated by fibroblast growth factors and their receptors. This review highlights the role of these signaling pathways in the context of non-alcoholic fatty liver disease and non-alcoholic steatohepatitis and discusses novel treatment options for these otherwise difficult to treat diseases.