%0 Multicenter Study
%T Natural history of liver disease in a large international cohort of children with Alagille syndrome: Results from the GALA study.
%A Vandriel SM
%A Li LT
%A She H
%A Wang JS
%A Gilbert MA
%A Jankowska I
%A Czubkowski P
%A Gliwicz-Miedzińska D
%A Gonzales EM
%A Jacquemin E
%A Bouligand J
%A Spinner NB
%A Loomes KM
%A Piccoli DA
%A D'Antiga L
%A Nicastro E
%A Sokal É
%A Demaret T
%A Ebel NH
%A Feinstein JA
%A Fawaz R
%A Nastasio S
%A Lacaille F
%A Debray D
%A Arnell H
%A Fischler B
%A Siew S
%A Stormon M
%A Karpen SJ
%A Romero R
%A Kim KM
%A Baek WY
%A Hardikar W
%A Shankar S
%A Roberts AJ
%A Evans HM
%A Jensen MK
%A Kavan M
%A Sundaram SS
%A Chaidez A
%A Karthikeyan P
%A Sanchez MC
%A Cavalieri ML
%A Verkade HJ
%A Lee WS
%A Squires JE
%A Hajinicolaou C
%A Lertudomphonwanit C
%A Fischer RT
%A Larson-Nath C
%A Mozer-Glassberg Y
%A Arikan C
%A Lin HC
%A Bernabeu JQ
%A Alam S
%A Kelly DA
%A Carvalho E
%A Ferreira CT
%A Indolfi G
%A Quiros-Tejeira RE
%A Bulut P
%A Calvo PL
%A Önal Z
%A Valentino PL
%A Desai DM
%A Eshun J
%A Rogalidou M
%A Dezsőfi A
%A Wiecek S
%A Nebbia G
%A Pinto RB
%A Wolters VM
%A Tamara ML
%A Zizzo AN
%A Garcia J
%A Schwarz K
%A Beretta M
%A Sandahl TD
%A Jimenez-Rivera C
%A Kerkar N
%A Brecelj J
%A Mujawar Q
%A Rock N
%A Busoms CM
%A Karnsakul W
%A Lurz E
%A Santos-Silva E
%A Blondet N
%A Bujanda L
%A Shah U
%A Thompson RJ
%A Hansen BE
%A Kamath BM
%A  
%J Hepatology
%V 77
%N 2
%D 02 2023 1
%M 36036223
%F 17.298
%R 10.1002/hep.32761
%X 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.<BR>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).<BR>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.