Rencofilstat Treatment Improves Liver Function in MASH With Advanced Fibrosis as Quantified by HepQuant DuO

• Published in: Liver international Vol. 45; no. 3; pp. e70036 - n/a
• Main Authors: Harrison, Stephen A., Mayo, Patrick, Hobbs, Todd, Zhao, Caroline, Canizares, Carlos, Foster, Robert, McRae, Michael P., Helmke, Steve M., Everson, Gregory T.
• Format: Journal Article
• Language: English
• Published: United States Wiley Subscription Services, Inc 01.03.2025
• Subjects: Adult; Aged; Biopsy; cholate clearance; Female; Fibrosis; Humans; Hypertension, Portal - drug therapy; Liver; Liver - drug effects; Liver - pathology; Liver - physiopathology; Liver Cirrhosis - drug therapy; Liver Cirrhosis - physiopathology; liver fibrosis; Liver Function Tests; Male; metabolic dysfunction‐associated steatohepatitis; Middle Aged; quantitative liver function test; Severity of Illness Index; Shunts; Treatment Outcome; liver fibrosis; metabolic dysfunction‐associated steatohepatitis; cholate clearance; quantitative liver function test
• DOI: 10.1111/liv.70036
• ISSN: 1478-3223; 1478-3231

ABSTRACT Background and Aims Rencofilstat inhibits cyclophilin to reduce hepatic inflammation and fibrosis, which, in turn, could improve liver function and reduce portal‐systemic shunting. Since HepQuant quantifies liver function and portal‐systemic shunting, it was used to measure the hepatic effects of rencofilstat treatment of MASH with advanced fibrosis. Methods Seventy subjects with suspected ≥ F3 MASH, defined from liver biopsy or AGILE 3+ ≥ 0.53, were randomised to rencofilstat 75 mg/d (n = 24), 150 mg/d (n = 23) or 225 mg/d (n = 23), and tested by HepQuant at baseline, 60 and 120 days. The DuO version included oral dosing of d4‐cholate and two blood samples (20 and 60 min). DuO's disease severity index (DSI) and portal‐systemic shunting fraction (SHUNT%) were evaluated for changes from baseline at 60 and 120 days of rencofilstat treatment. Results Across all subjects, there was a significant decrease in SHUNT% both at Day 60 (−1.67%, p = 0.0156) and Day 120 (−1.55%, p = 0.0441). In the 225 mg rencofilstat arm, 56% of subjects (10/18) were responders by Day 120 (p = 0.0549), and their DSIs improved with a mean change of −1.61 (p = 0.0190). Across all treatment arms, subjects with DSI > 18.3 at baseline had the greatest improvement with treatment (ΔDSI = −2.59, p = 0.0053). Conclusion Although further studies are warranted, the decreases in DSI and SHUNT% suggest that rencofilstat 225 mg/d improves hepatic function and portal‐systemic shunting. HepQuant DuO is simple to administer, well‐tolerated and a useful tool for detecting the hepatic effects of treatment. Trial Registration The study was registered at ClinicalTrials.gov, NCT05461105