Insights into the molecular targets and emerging pharmacotherapeutic interventions for nonalcoholic fatty liver disease

Metabolism. 2022 Jan;126:154925. doi: 10.1016/j.metabol.2021.154925. Epub 2021 Nov 2.

Abstract

Nonalcoholic fatty liver disease (NAFLD) is the most common form of chronic liver disease worldwide. With no Food and Drug Administration approved drugs, current treatment options include dietary restrictions and lifestyle modification. NAFLD is closely associated with metabolic disorders such as obesity, type 2 diabetes, and dyslipidemia. Hence, clinically various pharmacological approaches using existing drugs such as antidiabetic, anti-obesity, antioxidants, and cytoprotective agents have been considered in the management of NAFLD and nonalcoholic steatohepatitis (NASH). However, several pharmacological therapies aiming to alleviate NAFLD-NASH are currently being examined at various phases of clinical trials. Emerging data from these studies with drugs targeting diverse molecular mechanisms show promising outcomes. This review summarizes the current understanding of the pathogenic mechanisms of NAFLD and provides an insight into the pharmacological targets and emerging therapeutics with specific interventional mechanisms. In addition, we also discuss the importance and utility of new approach methodologies and regulatory perspectives for NAFLD-NASH drug development.

Keywords: Clinical trials; Drug therapy; Nonalcoholic fatty liver disease (NAFLD); Nonalcoholic steatohepatitis (NASH); Novel targets.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Antioxidants / therapeutic use
  • Drug Design
  • Humans
  • Liver / metabolism*
  • Non-alcoholic Fatty Liver Disease / drug therapy*
  • Non-alcoholic Fatty Liver Disease / metabolism

Substances

  • Antioxidants