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

Table 1 Studies of cyclophilin inhibitors 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 end points	Key findings
Harrison et al[9], 2022	Human	Randomized, single-blind, placebo-controlled, phase 2a study; Duration: 4 wk	n = 49	Patients with presumed F2/F3 NASH	Rencofilstat Placebo vs Rencofilstat (75 or 225 mg daily)	Evaluate the effect of Rencofilstat on ALT, Pro-C3, liver steatosis, and fibrosis measured by FibroScan	ALT in the placebo vs 75 vs 225 mg group was 70.67 vs 42.5 vs 30.56 IU/L. Pro-C3 was reduced in stratified patients with Pro-C3 > 15 (P < 0.01). Fibrosis was 22 vs 14 vs 12 kPa. Steatosis was 351 vs 337 vs 329 dB/m
Kuo et al[6], 2019	Animal	Duration: 30 wk	n = 10	High-fat diet-induced NASH mouse model (n = 10)	CRV431: Control vs 50 mg/kg daily	Evaluate the effect of CRV431 on liver fibrosis measured by Sirius red staining in liver biopsy sections	Fibrosis levels were 37%–46% lower in the treatment vs control group (P < 0.05)
Kuo et al[8], 2019	Animal	Duration: 6 wk	n = 9	CCL4-induced liver fibrosis mouse model (n = 9)	CRV431: Control vs 50 mg/kg daily	Evaluate the effect of CRV431 on liver fibrosis measured by Sirius red staining in liver biopsy sections	Liver fibrosis was lowered by 43% in the treatment vs control group (P < 0.01)
Kuo et al[8], 2019	Animal	Duration: 6 wk	n = 8	High-fat diet-induced NASH mouse model	NV556: Control vs 50 mg/kg daily	Evaluate the effect of NV556 on liver collagen and fibrosis measured by Sirius red staining in liver biopsy sections	Fibrosis was reduced by 60% in the treatment vs control group (P = 0.0281)
Simón Serrano et al[7], 2019	Animal	Duration: 7 wk	n = 20	Choline-deficient high-fat diet-induced model of NASH in mice (n = 10 per group)	NV556: Control vs 100 mg/kg daily	Effect of NV556 on liver fibrosis and collagen production measured by Sirus red staining	Reduction of liver fibrosis by 25% (2% in control vs 1.5% in treatment group P < 0.01)

ALT: Alanine transaminase; AST: Aspartate aminotransferase; NASH: Non-alcoholic steatohepatitis; NAFLD: Non-alcoholic fatty liver disease; CCL4: Carbon tetrachloride; IU: International units.