Emerging therapeutic options for non-alcoholic fatty liver disease: A systematic review

Table 2 Studies of fibroblast growth factor analogs/agonists in the treatment of non-alcoholic fatty liver disease

Ref.	Human or animal	Study design	Number of participants	Key inclusion criteria	Investigational product/dose	Study endpoints	Key findings
Harrison et al[10], 2021	Human	Randomized, double-blind, placebo-controlled, phase 2a BALANCED study. Duration: 16 wk	n = 80	Patients with biopsy-confirmed NASH (F1-F3)	Efruxifermin: Placebo vs EFX (28, 50, 70 mg)	Absolute change from baseline in HFF measured as MRI-proton density fat fraction at 12 wk of EFX	The mean relative change in HFF at week 12 was -63.2% -70.9%, and -72.3%, respectively, in the treatment groups of 28, 50, and 70 mg (P < 0.0001)
Bao et al[12], 2018	Animal	Duration: 15 d	n = 10	Choline-deficient high-fat diet-induced model of NASH in mice (n = 5 per group)	PsTag600 Control vs 3.7 mg/kg-1 daily	Effect of PSTag600 on attenuation of the development of NASH measured by NAS and oil red O staining	Decrease in NAS in control vs treatment group of 5 vs 1 and area of oil red O of 26% vs 3%, respectively (P < 0.05)
Le et al[11], 2018	Animal	Duration: 4 wk	n = 8	MCD diet-induced NASH mouse model	LY2405319 Control vs 1.5 mg/kg daily	Evaluate the attenuation of fibrosis with the administration of LY2405319 by measuring levels of a-SMA and GPR91 (cells and receptors involved in hepatic fibrogenesis) on liver biopsy after 8 wk	The expression of α-SMA and GPR91 in the liver of mice fed with MCD diet was increased. The treatment group had an attenuated increase of collagen type 1, α-SMA, and GPR91 protein levels (P < 0.05). LY2405319 intraperitoneal administration for 4 wk daily ameliorated hepatic steatosis and fibrosis that was induced by MCD diet
Puengel et al[13], 2022	Animal	Duration: 6 wk	n = 12	Choline-deficient high-fat diet-induced model of NASH in mice (n = 6 per group)	BMS-986171: Control vs 0.6 mg/kg twice weekly	Effect of BMS-986171 on liver steatosis and fibrosis measured NAS on biopsy	NAS of the control vs. treatment group was 5 vs 4 (P < 0.05), hepatic steatosis 2.5 vs 1.5 (P < 0.01), inflammation 3.5 vs 2.5 and ballooning 1.2 vs 0.75 (P < 0.001) respectively

NASH: Non-alcoholic steatohepatitis; n: Number; NAS: NAFLD activity score; EFX: Efruxifermin; HFF: Hepatic fat fraction; MRI: Magnetic resonance imaging; α-SMA: Alpha-smooth muscle actin; MCD: Methionine and choline-deficient.