The burden of Alagille syndrome: uncovering the potential of emerging therapeutics - a comprehensive systematic literature review.

Aim: Alagille syndrome (ALGS) is a rare, cholestatic multiorgan disease associated with bile duct paucity, leading to cholestasis. Clinical symptoms of cholestasis include debilitating pruritus, xanthomas, fat-soluble vitamin deficiencies, growth failure, renal disease and impaired health-related quality of life (HRQoL). The main objective was to review the current literature on the epidemiological, clinical, psychosocial and economic burden of ALGS in view of the development of ileal bile acid transporter (IBAT) inhibitors.

Methods

Electronic literature databases were searched in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses checklist.

Results

330 publications were screened, 119 were relevant: 11 randomized controlled trials (RCTs), 21 non-RCTs, 10 HRQoL studies, two studies assessing cost/resource use and 77 epidemiological studies across several databases through 31 July 2024. Studies confirm that patients with ALGS experience cardiac anomalies, impaired growth, renal disease, poor HRQoL, fat-soluble vitamin deficiencies and debilitating pruritus; until the approval of IBAT inhibitors for the treatment of cholestatic pruritus in patients with ALGS, supportive management was the standard of care.

Conclusion

This review confirms the substantial clinical, economic and HRQoL burden associated with ALGS and consolidates current treatment evidence. Data from recent trials in ALGS demonstrate the potential impact of IBAT inhibitors to transform lives by improving cholestatic pruritus symptoms, HRQoL and native liver survival.