Future trends in the treatment of non-alcoholic steatohepatitis

Abstract

With an estimated prevalence of ≈25% in Western and Asian countries, non alcoholic fatty liver disease (NAFLD), caused by chronic excessive caloric intake, is the emerging as the most prevalent liver disorder worldwide. NAFLD exists in two clinical entities, non-alcoholic fatty liver disease (NAFL), a relative benign disease that carry on minimal risk of liver-related morbidity but significant risk of cardiovascular complications, and non-alcoholic steatohepatitis (NASH), a progressive liver disorder with a significant risk for development of liver-related morbidities and mortality. While, liver injury in NASH is contributed by lipid overload in hepatocytes, lipotoxicity, the main determinant of disease progression is an inflammation-driven fibrotic response. Here, we review the landscape of emerging pharmacological interventions in the treatment of NAFL and NASH. A consensus exists that, while treating the liver component of NASH requires development of novel pharmacological approaches, the future therapy of NASH needs to be tailored to the single patient and most likely will be a combination of agents acting on specific pathogenic mechanisms at different disease stage.

Keywords: Apoptosis; FXR; Fibrosis; GPBAR1; Inflammation; Intestine; Lipids; Liver; Nuclear receptors; PPARs; Steatohepatitis.