Alimentary pharmacology & therapeutics · 2026
Review Article: Ileal Bile Acid Transport (IBAT) Inhibitors as an Emerging Treatment for Cholestatic Liver Disease.
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Peverelle Matthew, Campbell Samantha M A, Peverelle James, Shah Sital, Greener Kate, Joshi Deepak, Nayagam Jeremy S
Аннотация
BACKGROUND: Cholestatic liver diseases such as Alagille syndrome (ALGS), progressive familial intrahepatic cholestasis (PFIC), primary biliary cholangitis (PBC) and primary sclerosing cholangitis (PSC) cause significant morbidity and mortality. Chronic pruritus is common, debilitating, and impairs health-related quality of life. Recently, pharmacological inhibition of the ileal bile acid transporter (IBAT) has emerged as a therapeutic target.
AIMS: To review the current landscape of IBAT inhibitors, summarise emerging clinical data, discuss their role in the treatment of cholestatic liver diseases and future directions for their development and use.
METHODS: This narrative review summarises current data on IBAT inhibitors, exploring their mechanisms, efficacy, and safety across ALGS, PFIC, PBC and PSC. References were identified through searches of PubMed from January 2000 to August 2025.
RESULTS: In phase 2 and 3 trials involving paediatric patients with ALGS and PFIC, IBAT inhibitors (odevixibat and maralixibat) significantly reduced pruritus and serum bile acid concentrations. In post hoc analysis, responders demonstrated improved event-free and transplant-free survival compared to historic control cohorts. The phase 3 trial of linerixibat in PBC demonstrated an improvement in pruritus compared to placebo. Mild to moderate gastrointestinal side effects, most commonly diarrhoea and abdominal discomfort, are common with IBAT inhibition, particularly in PBC and PSC.
CONCLUSIONS: IBAT inhibitors represent the first upstream pharmacotherapy targeting enterohepatic bile acid recirculation and are effective at reducing pruritus in ALGS and PFIC. Their role in PBC and PSC is promising yet undefined. Long-term studies are needed to assess effects on fibrosis progression, hepatocellular carcinoma risk and transplant-free survival.
AIMS: To review the current landscape of IBAT inhibitors, summarise emerging clinical data, discuss their role in the treatment of cholestatic liver diseases and future directions for their development and use.
METHODS: This narrative review summarises current data on IBAT inhibitors, exploring their mechanisms, efficacy, and safety across ALGS, PFIC, PBC and PSC. References were identified through searches of PubMed from January 2000 to August 2025.
RESULTS: In phase 2 and 3 trials involving paediatric patients with ALGS and PFIC, IBAT inhibitors (odevixibat and maralixibat) significantly reduced pruritus and serum bile acid concentrations. In post hoc analysis, responders demonstrated improved event-free and transplant-free survival compared to historic control cohorts. The phase 3 trial of linerixibat in PBC demonstrated an improvement in pruritus compared to placebo. Mild to moderate gastrointestinal side effects, most commonly diarrhoea and abdominal discomfort, are common with IBAT inhibition, particularly in PBC and PSC.
CONCLUSIONS: IBAT inhibitors represent the first upstream pharmacotherapy targeting enterohepatic bile acid recirculation and are effective at reducing pruritus in ALGS and PFIC. Their role in PBC and PSC is promising yet undefined. Long-term studies are needed to assess effects on fibrosis progression, hepatocellular carcinoma risk and transplant-free survival.