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. 2025 Feb;14(2):e240188.
doi: 10.57264/cer-2024-0188. Epub 2025 Jan 14.

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

Philip Bufler  1   2 , Robin Howard  3 , Lucia Quadrado  3 , Guy Lacey  3 , Jolan Terner-Rosenthal  3 , Andrea Goldstein  3 , Pamela Vig  3 , Deirdre Kelly  4   5
Affiliations

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

Philip Bufler et al. J Comp Eff Res. 2025 Feb.

Abstract

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.

Keywords: ALGS; Alagille syndrome; cholestasis; health-related quality of life; pruritus.

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Conflict of interest statement

Competing interests disclosure

P Bufler has nothing to disclose. R Howard, L Quadrado, G Lacey, J Terner-Rosenthal, A Goldstein and P Vig are employees of and shareholders in Mirum Pharmaceuticals, Inc. D Kelly has received grants from Albireo, AbbVie, Gilead Sciences and Mirum Pharmaceuticals, Inc., is a consultant for Alnylam, Intercept, Mirum Pharmaceuticals, Inc., Takeda, Freeline, GSK, Orphalan, Albireo and Astra Zeneca and has received honoraria from Mirum Pharmaceuticals, Inc. The authors have no other competing interests or relevant affiliations with any organization/entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

References

    1. Kamath BM, Baker A, Houwen R, Todorova L, Kerkar N. Systematic review: the epidemiology, natural history, and burden of Alagille syndrome. J. Pediatr. Gastroenterol. Nutr. 67(2), 148–156 (2018). - PMC - PubMed
    1. Saleh M, Kamath BM, Chitayat D. Alagille syndrome: clinical perspectives. Appl Clin Genet. 9, 75–82 (2016). - PMC - PubMed
    1. Turnpenny PD, Ellard S. Alagille syndrome: pathogenesis, diagnosis and management. Eur. J. Hum. Genet. 20(3), 251–257 (2012). - PMC - PubMed
    1. Li L, Krantz ID, Deng Y et al. Alagille syndrome is caused by mutations in human JAGGED1, which encodes a ligand for NOTCH1. Nat. Genet. 16(3), 243–251 (1997). - PubMed
    1. McDaniell R, Warthen DM, Sanchez-Lara PA et al. NOTCH2 mutations cause Alagille syndrome, a heterogeneous disorder of the notch signaling pathway. Am. J. Hum. Genet. 79(1), 169–173 (2006). - PMC - PubMed

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