TY - JOUR
T1 - Natural history of liver disease in a large international cohort of children with Alagille syndrome
T2 - Results from the GALA study
AU - The Global ALagille Alliance (GALA) Study Group
AU - Vandriel, Shannon M.
AU - Li, Li Ting
AU - She, Huiyu
AU - Wang, Jian She
AU - Gilbert, Melissa A.
AU - Jankowska, Irena
AU - Czubkowski, Piotr
AU - Gliwicz-Miedzińska, Dorota
AU - Gonzales, Emmanuel M.
AU - Jacquemin, Emmanuel
AU - Bouligand, Jérôme
AU - Spinner, Nancy B.
AU - Loomes, Kathleen M.
AU - Piccoli, David A.
AU - D'Antiga, Lorenzo
AU - Nicastro, Emanuele
AU - Sokal, Atienne
AU - Demaret, Tanguy
AU - Ebel, Noelle H.
AU - Feinstein, Jeffrey A.
AU - Fawaz, Rima
AU - Nastasio, Silvia
AU - Lacaille, Florence
AU - Debray, Dominique
AU - Arnell, Henrik
AU - Fischler, Björn
AU - Siew, Susan
AU - Stormon, Michael
AU - Karpen, Saul J.
AU - Romero, Rene
AU - Kim, Kyung Mo
AU - Baek, Woo Yim
AU - Hardikar, Winita
AU - Shankar, Sahana
AU - Roberts, Amin J.
AU - Evans, Helen M.
AU - Jensen, M. Kyle
AU - Kavan, Marianne
AU - Sundaram, Shikha S.
AU - Chaidez, Alexander
AU - Karthikeyan, Palaniswamy
AU - Sanchez, Maria Camila
AU - Cavalieri, Maria Lorena
AU - Verkade, Henkjan J.
AU - Lee, Way Seah
AU - Squires, James E.
AU - Hajinicolaou, Christina
AU - Lertudomphonwanit, Chatmanee
AU - Fischer, Ryan T.
AU - Quiros-Tejeira, Ruben E.
N1 - Publisher Copyright:
© 2023 John Wiley and Sons Inc.. All rights reserved.
PY - 2023/2
Y1 - 2023/2
N2 - 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.
AB - 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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U2 - 10.1002/hep.32761
DO - 10.1002/hep.32761
M3 - Article
C2 - 36036223
AN - SCOPUS:85138168945
SN - 0270-9139
VL - 77
SP - 512
EP - 529
JO - Hepatology
JF - Hepatology
IS - 2
ER -