Natural history of liver disease in a large international cohort of children with Alagille syndrome: Results from the GALA study
(2023) Hepatology — Vol. 77, n° 2, p. 512-529 (2023)
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Vandriel, Shannon M. 
She, Huiyu Sokal, Etienne
- Abstract
- (en) BACKGROUND AND AIMS: Alagille syndrome (ALGS) is a multisystem disorder, characterized by cholestasis. Existing outcome data are largely derived from tertiary centers, and real-world data are lacking. This study aimed to elucidate the natural history of liver disease in a contemporary, international cohort of children with ALGS. APPROACH AND RESULTS: This was a multicenter retrospective study of children with a clinically and/or genetically confirmed ALGS diagnosis, born between January 1997 and August 2019. Native liver survival (NLS) and event-free survival rates were assessed. Cox models were constructed to identify early biochemical predictors of clinically evident portal hypertension (CEPH) and NLS. In total, 1433 children (57% male) from 67 centers in 29 countries were included. The 10 and 18-year NLS rates were 54.4% and 40.3%. By 10 and 18 years, 51.5% and 66.0% of children with ALGS experienced ≥1 adverse liver-related event (CEPH, transplant, or death). Children (>6 and ≤12 months) with median total bilirubin (TB) levels between ≥5.0 and <10.0 mg/dl had a 4.1-fold (95% confidence interval [CI], 1.6-10.8), and those ≥10.0 mg/dl had an 8.0-fold (95% CI, 3.4-18.4) increased risk of developing CEPH compared with those <5.0 mg/dl. Median TB levels between ≥5.0 and <10.0 mg/dl and >10.0 mg/dl were associated with a 4.8 (95% CI, 2.4-9.7) and 15.6 (95% CI, 8.7-28.2) increased risk of transplantation relative to <5.0 mg/dl. Median TB <5.0 mg/dl were associated with higher NLS rates relative to ≥5.0 mg/dl, with 79% reaching adulthood with native liver ( p < 0.001). CONCLUSIONS: In this large international cohort of ALGS, only 40.3% of children reach adulthood with their native liver. A TB <5.0 mg/dl between 6 and 12 months of age is associated with better hepatic outcomes. These thresholds provide clinicians with an objective tool to assist with clinical decision-making and in the evaluation of therapies.
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Vandriel, S. M., Li, L.-T., She, H., Wang, J.-S., Gilbert, M. A., Jankowska, I., Czubkowski, P., Gliwicz‐Miedzińska, D., Gonzales, E. M., Jacquemin, E., Bouligand, J., Spinner, N. B., Loomes, K. M., Piccoli, D. A., D’Antiga, L., Nicastro, E., Sokal, E., Demaret, T., Ebel, N. H., et al. (2023). Natural history of liver disease in a large international cohort of children with Alagille syndrome: Results from the GALA study. Hepatology, 77(2), 512-529. https://doi.org/10.1002/hep.32761 (Original work published 2023)