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, fatsoluble vitamin deficiencies, growth failure, renal disease and impaired health-related q...
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| Format: | Article |
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Becaris Publishing Limited
2025-01-01
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| Series: | Journal of Comparative Effectiveness Research |
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| author | Philip Bufler Robin Howard Lucia Quadrado Guy Lacey Jolan Terner-Rosenthal Andrea Goldstein Pamela Vig Deirdre Kelly |
| author_facet | Philip Bufler Robin Howard Lucia Quadrado Guy Lacey Jolan Terner-Rosenthal Andrea Goldstein Pamela Vig Deirdre Kelly |
| author_sort | Philip Bufler |
| collection | DOAJ |
| description | 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, fatsoluble
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. |
| format | Article |
| id | doaj-art-8900b26e0036418e9c1d09898df3d38c |
| institution | Kabale University |
| issn | 2042-6313 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Becaris Publishing Limited |
| record_format | Article |
| series | Journal of Comparative Effectiveness Research |
| spelling | doaj-art-8900b26e0036418e9c1d09898df3d38c2025-01-27T15:30:36ZengBecaris Publishing LimitedJournal of Comparative Effectiveness Research2042-63132025-01-0114210.57264/cer-2024-0188The burden of Alagille syndrome: uncovering the potential of emerging therapeutics – a comprehensive systematic literature reviewPhilip Bufler0https://orcid.org/0000-0002-5742-8273Robin Howard1https://orcid.org/0000-0002-3405-2103Lucia Quadrado2https://orcid.org/0009-0003-8850-2266Guy Lacey3https://orcid.org/0009-0008-6048-4074Jolan Terner-Rosenthal4https://orcid.org/0009-0008-0315-3383Andrea Goldstein5https://orcid.org/0000-0001-5607-818XPamela Vig6https://orcid.org/0009-0000-4226-5435Deirdre Kelly7Department of Pediatric Gastroenterology, Nephrology & Metabolic Diseases, Charite – Universitatsmedizin Berlin, Berlin, Germany; German Center for Child & Adolescent Health (DZKJ), partner site Berlin, Berlin, GermanyMirum Pharmaceuticals, Inc., Foster City, CA, USAMirum Pharmaceuticals, Inc., Foster City, CA, USAMirum Pharmaceuticals, Inc., Foster City, CA, USAMirum Pharmaceuticals, Inc., Foster City, CA, USAMirum Pharmaceuticals, Inc., Foster City, CA, USAMirum Pharmaceuticals, Inc., Foster City, CA, USAGuy’s & St Thomas’ NHS Foundation Trust, London, UK; Evelina London Women’s & Children’s Clinical Group, Evelina London Children’s Hospital, London, UKAim: 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, fatsoluble 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.alagille syndromealgscholestasishealth-related quality of lifepruritus |
| spellingShingle | Philip Bufler Robin Howard Lucia Quadrado Guy Lacey Jolan Terner-Rosenthal Andrea Goldstein Pamela Vig Deirdre Kelly The burden of Alagille syndrome: uncovering the potential of emerging therapeutics – a comprehensive systematic literature review Journal of Comparative Effectiveness Research alagille syndrome algs cholestasis health-related quality of life pruritus |
| title | The burden of Alagille syndrome: uncovering the potential of emerging therapeutics – a comprehensive systematic literature review |
| title_full | The burden of Alagille syndrome: uncovering the potential of emerging therapeutics – a comprehensive systematic literature review |
| title_fullStr | The burden of Alagille syndrome: uncovering the potential of emerging therapeutics – a comprehensive systematic literature review |
| title_full_unstemmed | The burden of Alagille syndrome: uncovering the potential of emerging therapeutics – a comprehensive systematic literature review |
| title_short | The burden of Alagille syndrome: uncovering the potential of emerging therapeutics – a comprehensive systematic literature review |
| title_sort | burden of alagille syndrome uncovering the potential of emerging therapeutics a comprehensive systematic literature review |
| topic | alagille syndrome algs cholestasis health-related quality of life pruritus |
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