NAFLD in 2014: Genetics, diagnostics and therapeutic advances in NAFLD

Abstract

In 2014, NAFLD was confirmed as the fastest growing aetiology for hepatocellular cancer in the USA. However, 2014 also saw progress in our understanding of the heritability and pathogenesis of NAFLD, and an important clinical trial targeting the farnesoid X receptor pathway has illustrated advances in developing a pharmacological therapy.

Conflict of interest statement

Competing interests

M.E.R. has served as a consultant to AbbVie, Fibrogen, Genentech, NGM Biopharmaceuticals, Takeda and W.L. Gore and Associates. A.J.S. has stock options in Genfit. He has served as a consultant to AbbVie, Astra Zeneca, Exhalenz, Fibrogen, Genfit, Immuron, Nimbus, Nitto Denko, Salix, Takeda and Tobira. He has been an unpaid consultant to Echosens and Intercept. His institution has received grant support from Gilead, Novartis, Salix and Tobira.

Figures

Figure 1

Potential effects of obeticholic acid on NASH. Bile acid ligands bind to FXR, which forms a heterodimer with RXR and reduces bile acid synthesis via CYP7a1 inhibition. FXR is involved in many metabolic processes that regulate lipid and glucose metabolism. Obeticholic acid, a semi-synthetic bile acid ligand for FXR, 100× more potent than its natural ligand, might be able to ameliorate several metabolic derangements seen in NASH such as hepatic steatosis, glucose tolerance, inflammation and even hepatic fibrosis by inhibiting hepatic stellate cell activity. Abbreviations: CYP7a1, cytochrome P450 7A1; FXR, farnesoid X receptor; RXR, retinoid X receptor.