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

• Published in: Metabolism, clinical and experimental Vol. 126; p. 154925
• Main Authors: Negi, Chander K., Babica, Pavel, Bajard, Lola, Bienertova-Vasku, Julie, Tarantino, Giovanni
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.01.2022
• Subjects: Antioxidants - therapeutic use; Clinical trials; Drug Design; Drug therapy; Humans; Liver - metabolism; Non-alcoholic Fatty Liver Disease - drug therapy; Non-alcoholic Fatty Liver Disease - metabolism; Nonalcoholic fatty liver disease (NAFLD); Nonalcoholic steatohepatitis (NASH); Novel targets; FFA; MPC; TNFα; JNK; HFD; ALT; HDL-C; OECD; PPAR; VLDL; EMA; iNOS; TIMP1; NAFL/NAFLD; IL; FGF; JAK-STAT; HVPG; DDP-4; HCC; SCD-1; CCR2/CCR5; ER; IBAT; GIP; MRI-PDFF; TLR4; IND; FXR; T2DM; FDA; THR-β; COX-2; LDL-C; LXR; Clinical trials; HSD17B13; NDA; CYP7A1; EASD; LPS; DPP4; PRIME; Novel targets; EASL; CCKR; EASO; AASLD; GC; Drug therapy; HbA1c; MOA; BMI; IFNs; ACC; AOP; AST; GLP-1; SGLT2; ASK1; IKK; DGAT; CCK; siRNA; NASH; Nonalcoholic steatohepatitis (NASH); MAFLD; TG; GGT; GHRH; PNPLA3; FAS; Nonalcoholic fatty liver disease (NAFLD)
• ISSN: 0026-0495; 1532-8600
• DOI: 10.1016/j.metabol.2021.154925

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.