IBAT INHIBITION IN CHRONIC CHOLESTATIC LIVER DISEASES: FROM PRURITUS CONTROL TO POTENTIAL DISEASE MODIFICATION

ackground Chronic cholestatic liver diseases disrupt bile acid homeostasis and may cause severe pruritus that impairs quality of life. Conventional treatments often provide incomplete relief. Ileal bile acid transporter (IBAT) inhibition reduces enterohepatic bile acid recirculation, offering a targeted approach to cholestatic pruritus. Aim To synthesize the current evidence on IBAT inhibition in chronic cholestatic liver diseases, focusing on its mechanisms of action, efficacy in controlling pruritus, effects on liver-related outcomes, safety, and potential for disease modification. Materials and Methods PubMed, Google Scholar, and ClinicalTrials.gov were searched for publications from January 2016 to August 2026; the final search was on 25 August 2026. Clinical, observational, preclinical, and guideline-based evidence on IBAT inhibition in chronic cholestatic liver diseases was narratively synthesized, focusing on efficacy, safety, liver-related outcomes, and potential disease modification. Results IBAT inhibitors reduced pruritus and serum bile acids in several cholestatic disorders, with effects varying across studies. Odevixibat and maralixibat improved pruritus in PFIC and Alagille syndrome, while linerixibat showed efficacy in PBC. Evidence for volixibat remains preliminary. Observational associations with improved native liver and event-free survival do not establish disease modification. Diarrhea was the most common adverse event; fat-soluble vitamin deficiency and liver test abnormalities are additional safety concerns. Conclusions IBAT inhibition represents an established therapeutic approach for cholestatic pruritus in selected cholestatic disorders. However, its effects on long-term liver disease progression, the need for liver transplantation, and mortality remain unestablished. Further adequately powered, long-term studies using clinically meaningful endpoints are needed to determine whether sustained IBAT inhibition can modify the natural history of chronic cholestatic liver disease.