Table 1.

Therapeutic interventions for NAFLD/NASH.

Therapeutic intervention	Therapeutic agent	Molecular target	Effect on NALFD/NASH	Model	Ref
Inhibition of cholesterol synthesis	Statins	HMGCoAr	Protection against steatosis, steatohepatitis and fibrosis [assessed by liver biopsies]	Retrospective study-humans	(50)
	Simvastatin	HMGCoAr	Protects parenchymal and endothelial components of the liver after warm reperfusion.	Rat model of steatotic graft	(51)
	Fluvastatin	HMGCoAr	Reduced hepatic steatosis and fibrosis scores, α-SMA protein expression, mRNA expression of pro-inflammatory, and pro-fibrogenic genes	Choline-deficient L-amino acid-defined diet-induced Rat NASH model	(52)
	Simvastatin	RhoA and Ras signaling	Decreased hepatic inflammation and fibrosis. No effect on steatosis	Diet-induced NASH in apoE−/− mice	(53)
Inhibition of bile acid absorption	SC-435	ASBT	Restored glucose tolerance, reduced hepatic triglyceride and total cholesterol, improved NAFLD activity score	High fat diet-induced NAFLD in C57BL mice	(54)
	Volixibat	ASBT	Attenuated the hepatocyte hypertrophy, reduced hepatic triglyceride and cholesteryl ester levels, decreased NAFLD activity score	Diet-induced NASH in LDLr–/–/ Leiden mice	(55)
	Volixibat	ASBT	Interim-endpoint was not met and the study was terminated owing to lack of efficacy	Clinical trial-humans	(56)
Inhibition of cholesterol absorption	Ezetimibe	NPC1L1	Decreased hepatic cholesterol content and increased the hepatic total bile acid content, ameliorated hepatic insulin resistance	C57BL mice fed with high fat diet	(57)
	Ezetimibe	NPC1L1	Fibrosis stage and ballooning score were significantly improved with ezetimibe treatment [Histological evaluation]	Clinical trial-humans	(58)
	Ezetimibe	NPC1L1	Failed to reduce liver fat assessed by MRI-PDFF imaging	Clinical trial-humans	(59)
	Ezetimibe	NPC1L1	Decreased NAFLD activity score (NAS) but not hepatic steatosis	Meta-analysis of RCTs-humans	(60)