1. Natural history of liver disease in a large international cohort of children with Alagille syndrome: Results from the GALA study
- Author
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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, É. Demaret, T. Ebel, N.H. Feinstein, J.A. Fawaz, R. Nastasio, S. Lacaille, F. Debray, D. Arnell, H. Fischler, B. Siew, S. Stormon, M. Karpen, S.J. Romero, R. Kim, K.M. Baek, W.Y. Hardikar, W. Shankar, S. Roberts, A.J. Evans, H.M. Jensen, M.K. Kavan, M. Sundaram, S.S. Chaidez, A. Karthikeyan, P. Sanchez, M.C. Cavalieri, M.L. Verkade, H.J. Lee, W.S. Squires, J.E. Hajinicolaou, C. Lertudomphonwanit, C. Fischer, R.T. Larson-Nath, C. Mozer-Glassberg, Y. Arikan, C. Lin, H.C. Bernabeu, J.Q. Alam, S. Kelly, D.A. Carvalho, E. Ferreira, C.T. Indolfi, G. Quiros-Tejeira, R.E. Bulut, P. Calvo, P.L. Önal, Z. Valentino, P.L. Desai, D.M. Eshun, J. Rogalidou, M. Dezsőfi, A. Wiecek, S. Nebbia, G. Pinto, R.B. Wolters, V.M. Tamara, M.L. Zizzo, A.N. Garcia, J. Schwarz, K. Beretta, M. Sandahl, T.D. Jimenez-Rivera, C. Kerkar, N. Brecelj, J. Mujawar, Q. Rock, N. Busoms, C.M. Karnsakul, W. Lurz, E. Santos-Silva, E. Blondet, N. Bujanda, L. Shah, U. Thompson, R.J. Hansen, B.E. Kamath, B.M. The Global ALagille Alliance (GALA) Study Group and 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, É. Demaret, T. Ebel, N.H. Feinstein, J.A. Fawaz, R. Nastasio, S. Lacaille, F. Debray, D. Arnell, H. Fischler, B. Siew, S. Stormon, M. Karpen, S.J. Romero, R. Kim, K.M. Baek, W.Y. Hardikar, W. Shankar, S. Roberts, A.J. Evans, H.M. Jensen, M.K. Kavan, M. Sundaram, S.S. Chaidez, A. Karthikeyan, P. Sanchez, M.C. Cavalieri, M.L. Verkade, H.J. Lee, W.S. Squires, J.E. Hajinicolaou, C. Lertudomphonwanit, C. Fischer, R.T. Larson-Nath, C. Mozer-Glassberg, Y. Arikan, C. Lin, H.C. Bernabeu, J.Q. Alam, S. Kelly, D.A. Carvalho, E. Ferreira, C.T. Indolfi, G. Quiros-Tejeira, R.E. Bulut, P. Calvo, P.L. Önal, Z. Valentino, P.L. Desai, D.M. Eshun, J. Rogalidou, M. Dezsőfi, A. Wiecek, S. Nebbia, G. Pinto, R.B. Wolters, V.M. Tamara, M.L. Zizzo, A.N. Garcia, J. Schwarz, K. Beretta, M. Sandahl, T.D. Jimenez-Rivera, C. Kerkar, N. Brecelj, J. Mujawar, Q. Rock, N. Busoms, C.M. Karnsakul, W. Lurz, E. Santos-Silva, E. Blondet, N. Bujanda, L. Shah, U. Thompson, R.J. Hansen, B.E. Kamath, B.M. The Global ALagille Alliance (GALA) Study Group
- Abstract
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. © 2022 The Authors. Hepatology publ
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- 2022