Efficacy and Safety of Ileal Bile Acid Transport Inhibitors in Inherited Cholestatic Liver Disorders: A Meta-analysis of Randomized Controlled Trials.

Background: Inherited cholestatic liver disorders such as progressive familial intrahepatic cholestasis (PFIC) and Alagille syndrome result in significant pruritus and increased serum bile acids, necessitating liver transplantation. This study aims to evaluate the efficacy and safety of Ileal bile acid transport inhibitors (IBATIs) in children with PFIC and Alagille syndrome.

Methods: We conducted a comprehensive search across the databases to identify relevant randomized controlled trials (RCTs), and Covidence was used to screen eligible articles. All outcomes data were synthesized using risk ratios (RRs) or mean differences (MDs) with 95% confidence intervals (CIs) in RevMan 5.4. PROSPERO: CRD42024564270.

Results: Four multicenter RCTs involving 215 patients were included. IBATIs were associated with a significant reduction in Itch Observer Reported Outcome (Itch (ObsRo)) score (MD: -0.90, 95% CI [-1.17, -0.63],  < 0.01), serum bile acids (MD: -119.06, 95% CI [-152.37, -85.74],  < 0.01), total bilirubin (MD: -0.73, 95% CI [-1.32, -0.15],  = 0.01), and increased proportion of patients achieving ≥1 score reduction in Itch (ObsRo) score (RR: 2.54, 95% CI [3.83, 1.69],  < 0.01) and bile acid responders (RR: 8.76, 95% CI [2.46, 31.23],  < 0.01) compared with placebo. No differences were observed in any treatment-emergent adverse events (TEAs) (RR: 1.02, 95% CI [1.12, 0.93],  = 0.71), TEAs leading to drug discontinuation (1.03, 95% CI [5.56, 0.19], any serious TEAs, or liver-related TEAs.

Conclusion: IBATIs showed significant improvement in various cholestatic parameters with tolerable safety profile; however, future research on optimal dosage and long-term outcomes is needed.