Natural history of liver disease in a large international cohort of children with Alagille syndrome: Results from the GALA study

Vandriel, Shannon M.; Li, Li-Ting; She, Huiyu; Wang, Jian-She; Gilbert, Melissa A.; Jankowska, Irena; Czubkowski, Piotr; Gliwicz-Miedzinska, Dorota; Gonzales, Emmanuel M.; Jacquemin, Emmanuel; Bouligand, Jerome; 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, Bjorn; 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.; Bernabeu, Jesus Quintero; Alam, Seema; Kelly, Deirdre A.; Carvalho, Elisa; Ferreira, Cristina Targa; Indolfi, Giuseppe; Quiros-Tejeira, Ruben E.; Bulut, Pinar; Calvo, Pier Luigi; Onal, Zerrin; Valentino, Pamela L.; Desai, Dev M.; Eshun, John; Rogalidou, Maria; Dezsofi, Antal; Wiecek, Sabina; Nebbia, Gabriella; Pinto, Raquel Borges; Wolters, Victorien M.; Tamara, Maria Legarda; Zizzo, Andreanne 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. und Kamath, Binita M. (2022): Natural history of liver disease in a large international cohort of children with Alagille syndrome: Results from the GALA study. In: Hepatology, Bd. 77, Nr. 2: S. 512-529

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 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.

• Dokumententyp: Zeitschriftenartikel
• Fakultät: Medizin
• Themengebiete: 600 Technik, Medizin, angewandte Wissenschaften > 610 Medizin und Gesundheit
• ISSN: 0270-9139
• Sprache: Englisch