1. Natural History of Liver Disease in a Large International Cohort of Children with Alagille syndrome: Results from The <scp>GALA</scp> Study
- Author
-
UCL - SSS/IREC/PEDI - Pôle de Pédiatrie, UCL - (SLuc) Service de gastro-entérologie et hépatologie pédiatrique, Vandriel, Shannon M., Li, Li‐Ting, She, Huiyu, Wang, Jian‐She, Gilbert, Melissa A., Jankowska, Irena, Czubkowski, Piotr, Gliwicz‐Miedzińska, Dorota, Gonzales, Emmanuel M., Jacquemin, Emmanuel, Bouligand, Jérôme, Spinner, Nancy B., Loomes, Kathleen M., Piccoli, David A., D'Antiga, Lorenzo, Nicastro, Emanuele, Sokal, Etienne, Demaret,Tanguy, Ebel, Noelle H., Feinstein, Jeffrey A., Fawaz, Rima, Nastasio, Silvia, Lacaille, Florence, Debray, Dominique, Arnell, Henrik, Fischler, Björn, Siew, Susan, Stormon, Michael, Karpen, Saul J., Romero, Rene, Kim, Kyung Mo, Baek, Woo Yim, Hardikar, Winita, Shankar, Sahana, Roberts, Amin J., Evans, Helen M., Jensen, M. Kyle, Kavan, Marianne, Sundaram, Shikha S., Chaidez, Alexander, Karthikeyan, Palaniswamy, Sanchez, Maria Camila, Cavalieri, Maria Lorena, Verkade, Henkjan J., Lee, Way Seah, Squires, James E., Hajinicolaou, Christina, Lertudomphonwanit, Chatmanee, Fischer, Ryan T., Larson‐Nath, Catherine, Mozer‐Glassberg, Yael, Arikan, Cigdem, Lin, Henry C., Quintero Bernabeu, Jesus, Alam, Seema, Kelly, Deirdre, Carvalho, Elisa, Ferreira, Cristina Targa, Indolfi, Giuseppe, Quiros‐Tejeira, Ruben E., Bulut, Pinar, Calvo, Pier Luigi, Önal, Zerrin, Valentino, Pamela L., Desai, Dev M., Eshun, John, Rogalidou, Maria, Dezsőfi, Antal, Wiecek, Sabina, Nebbia, Gabriella, Borges Pinto, Raquel, Wolters, Victorien M., Tamara, María Legarda, Zizzo, Andréanne N., Garcia, Jennifer, Schwarz, Kathleen, Beretta, Marisa, Sandahl, Thomas Damgaard, Jimenez‐Rivera, Carolina, Kerkar, Nanda, Brecelj, Jernej, Mujawar, Quais, Rock, Nathalie, Busoms, Cristina Molera, Karnsakul, Wikrom, Lurz, Eberhard, Santos‐Silva, Ermelinda, Blondet, Niviann, Bujanda, Luis, Shah, Uzma, Thompson, Richard J., Hansen, Bettina E., Kamath, Binita M., UCL - SSS/IREC/PEDI - Pôle de Pédiatrie, UCL - (SLuc) Service de gastro-entérologie et hépatologie pédiatrique, Vandriel, Shannon M., Li, Li‐Ting, She, Huiyu, Wang, Jian‐She, Gilbert, Melissa A., Jankowska, Irena, Czubkowski, Piotr, Gliwicz‐Miedzińska, Dorota, Gonzales, Emmanuel M., Jacquemin, Emmanuel, Bouligand, Jérôme, Spinner, Nancy B., Loomes, Kathleen M., Piccoli, David A., D'Antiga, Lorenzo, Nicastro, Emanuele, Sokal, Etienne, Demaret,Tanguy, Ebel, Noelle H., Feinstein, Jeffrey A., Fawaz, Rima, Nastasio, Silvia, Lacaille, Florence, Debray, Dominique, Arnell, Henrik, Fischler, Björn, Siew, Susan, Stormon, Michael, Karpen, Saul J., Romero, Rene, Kim, Kyung Mo, Baek, Woo Yim, Hardikar, Winita, Shankar, Sahana, Roberts, Amin J., Evans, Helen M., Jensen, M. Kyle, Kavan, Marianne, Sundaram, Shikha S., Chaidez, Alexander, Karthikeyan, Palaniswamy, Sanchez, Maria Camila, Cavalieri, Maria Lorena, Verkade, Henkjan J., Lee, Way Seah, Squires, James E., Hajinicolaou, Christina, Lertudomphonwanit, Chatmanee, Fischer, Ryan T., Larson‐Nath, Catherine, Mozer‐Glassberg, Yael, Arikan, Cigdem, Lin, Henry C., Quintero Bernabeu, Jesus, Alam, Seema, Kelly, Deirdre, Carvalho, Elisa, Ferreira, Cristina Targa, Indolfi, Giuseppe, Quiros‐Tejeira, Ruben E., Bulut, Pinar, Calvo, Pier Luigi, Önal, Zerrin, Valentino, Pamela L., Desai, Dev M., Eshun, John, Rogalidou, Maria, Dezsőfi, Antal, Wiecek, Sabina, Nebbia, Gabriella, Borges Pinto, Raquel, Wolters, Victorien M., Tamara, María Legarda, Zizzo, Andréanne N., Garcia, Jennifer, Schwarz, Kathleen, Beretta, Marisa, Sandahl, Thomas Damgaard, Jimenez‐Rivera, Carolina, Kerkar, Nanda, Brecelj, Jernej, Mujawar, Quais, Rock, Nathalie, Busoms, Cristina Molera, Karnsakul, Wikrom, Lurz, Eberhard, Santos‐Silva, Ermelinda, Blondet, Niviann, Bujanda, Luis, Shah, Uzma, Thompson, Richard J., Hansen, Bettina E., and Kamath, Binita M.
- Abstract
Background: 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. Methods: Multicenter retrospective study of children with a clinically and/or genetically confirmed ALGS diagnosis, born Jan-1997 - Aug-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. Results: 1433 children (57% male) from 67 centers in 29 countries were included. 10 and 18-years NLS rates were 54.4% and 40.3%. By 10 and 18-years, 51.5% and 66.0% of ALGS children 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% 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 novel therapies.
- Published
- 2023