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Randomized Controlled Trial
. 2025 Mar;45(3):e70036.
doi: 10.1111/liv.70036.

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

Stephen A Harrison  1 , Patrick Mayo  2 , Todd Hobbs  2 , Caroline Zhao  2 , Carlos Canizares  2 , Robert Foster  2 , Michael P McRae  3 , Steve M Helmke  4 , Gregory T Everson  4
Affiliations
Randomized Controlled Trial

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

Stephen A Harrison et al. Liver Int. 2025 Mar.

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.

Keywords: cholate clearance; liver fibrosis; metabolic dysfunction‐associated steatohepatitis; quantitative liver function test.

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References

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