RENCOFILSTAT is a promising treatment aimed at reducing hepatic inflammation and fibrosis by inhibiting cyclophilin. This mechanism can potentially improve liver function and decrease portal-systemic shunting, which is vital for patients suffering from metabolic-associated steatotic hepatitis (MASH) with advanced fibrosis.
To evaluate its effects, HepQuant, a tool that quantifies liver function and portal-systemic shunting, was used in a study involving 70 subjects with suspected ≥F3 MASH. These patients were randomised to receive rencofilstat at doses of 75mg/d, 150mg/d, or 225mg/d for 120 days. The patients were assessed at baseline, 60, and 120 days using the DuO version of HepQuant, which involved oral dosing of d4-cholate and blood samples to measure disease severity index (DSI) and portal-systemic shunting fraction (SHUNT%).
Results showed a significant decrease in SHUNT% for all subjects, both at Day 60 (−1.67%, p = 0.0156) and Day 120 (−1.55%, p = 0.0441), indicating an improvement in portal-systemic shunting. Notably, the group receiving the highest rencofilstat dose (225mg/d) showed the most promising results, with 56% of subjects being responders by Day 120, along with a significant improvement in DSI (mean change of −1.61, p = 0.0190). Moreover, subjects who had a higher DSI at baseline (above 18.3) experienced the most significant improvement in both DSI and SHUNT%.
In conclusion, the study suggests that rencofilstat 225mg/d improves both liver function and portal-systemic shunting in MASH patients with advanced fibrosis. HepQuant DuO proved to be a simple, well-tolerated, and effective tool for detecting hepatic changes, although further studies are needed to confirm these findings and refine the treatment’s potential for broader clinical use.
Katie Wright, EMJ
Reference
Harrison SA et al. Rencofilstat treatment improves liver function in MASH with advanced fibrosis as quantified by HepQuant DuO. Liver Int. 2025;45(3):e70036.
