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

Shannon M. Vandriel; Li-Ting Li; Huiyu She; Jian-She Wang; Melissa A. Gilbert; Irena Jankowska; Piotr Czubkowski; Dorota Gliwicz-Miedzińska; Emmanuel M. Gonzales; Emmanuel Jacquemin; J. rôme Bouligand; Nancy B. Spinner; Kathleen M. Loomes; David A. Piccoli; Lorenzo D'Antiga; Emanuele Nicastro; Atienne Sokal; Tanguy Demaret; Noelle H. Ebel; Jeffrey A. Feinstein; Rima Fawaz; Silvia Nastasio; Florence Lacaille; Dominique Debray; Henrik Arnell; Björn Fischler; Susan Siew; Michael Stormon; Saul J. Karpen; Rene Romero; Kyung Mo Kim; Woo Yim Baek; Winita Hardikar; Sahana Shankar; Amin J. Roberts; Helen M. Evans; M. Kyle Jensen; Marianne Kavan; Shikha S. Sundaram; Alexander Chaidez; Palaniswamy Karthikeyan; Maria Camila Sanchez; Maria Lorena Cavalieri; Henkjan J. Verkade; Way Seah Lee; James E. Squires; Christina Hajinicolaou; Chatmanee Lertudomphonwanit; Ryan T. Fischer; Catherine Larson-Nath; Yael Mozer-Glassberg; Cigdem Arikan; Henry C. Lin; Jesus Quintero Bernabeu; Seema Alam; Deirdre A. Kelly; Elisa Carvalho; Cristina Targa Ferreira; Giuseppe Indolfi; Ruben E. Quiros-Tejeira; Pinar Bulut; Pier Luigi Calvo; Zerrin Anal; Pamela L. Valentino; Dev M. Desai; John Eshun; Maria Rogalidou; Antal Dezsőfi; Sabina Wiecek; Gabriella Nebbia; Raquel Borges Pinto; Victorien M. Wolters; María Legarda Tamara; Andréanne N. Zizzo; Jennifer Garcia; Kathleen Schwarz; Marisa Beretta; Thomas Damgaard Sandahl; Carolina Jimenez-Rivera; Nanda Kerkar; Jernej Brecelj; Quais Mujawar; Nathalie Rock; Cristina Molera Busoms; Wikrom Karnsakul; Eberhard Lurz; Ermelinda Santos-Silva; Niviann Blondet; Luis Bujanda; Uzma Shah; Richard J. Thompson; The Global ALagille Alliance (GALA) Study Group

doi:10.1002/hep.32761

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

Shannon M. Vandriel
, Li-Ting Li
, Huiyu She
, Jian-She Wang
, Melissa A. Gilbert
, Irena Jankowska
, Piotr Czubkowski
, Dorota Gliwicz-Miedzińska
, Emmanuel M. Gonzales
, Emmanuel Jacquemin
, J. rôme Bouligand
, Nancy B. Spinner
, Kathleen M. Loomes
, David A. Piccoli
, Lorenzo D'Antiga
, Emanuele Nicastro
, Atienne Sokal
, Tanguy Demaret
, Noelle H. Ebel
, Jeffrey A. Feinstein

Rima Fawaz, Silvia Nastasio, Florence Lacaille, Dominique Debray, Henrik Arnell, Björn Fischler, Susan Siew, Michael Stormon, Saul J. Karpen, Rene Romero, Kyung Mo Kim, Woo Yim Baek, Winita Hardikar, Sahana Shankar, Amin J. Roberts, Helen M. Evans, M. Kyle Jensen, Marianne Kavan, Shikha S. Sundaram, Alexander Chaidez, Palaniswamy Karthikeyan, Maria Camila Sanchez, Maria Lorena Cavalieri, Henkjan J. Verkade, Way Seah Lee, James E. Squires, Christina Hajinicolaou, Chatmanee Lertudomphonwanit, Ryan T. Fischer, Catherine Larson-Nath, Yael Mozer-Glassberg, Cigdem Arikan, Henry C. Lin, Jesus Quintero Bernabeu, Seema Alam, Deirdre A. Kelly, Elisa Carvalho, Cristina Targa Ferreira, Giuseppe Indolfi, Ruben E. Quiros-Tejeira, Pinar Bulut, Pier Luigi Calvo, Zerrin Anal, Pamela L. Valentino, Dev M. Desai, John Eshun, Maria Rogalidou, Antal Dezsőfi, Sabina Wiecek, Gabriella Nebbia, Raquel Borges Pinto, Victorien M. Wolters, María Legarda Tamara, Andréanne N. Zizzo, Jennifer Garcia, Kathleen Schwarz, Marisa Beretta, Thomas Damgaard Sandahl, Carolina Jimenez-Rivera, Nanda Kerkar, Jernej Brecelj, Quais Mujawar, Nathalie Rock, Cristina Molera Busoms, Wikrom Karnsakul, Eberhard Lurz, Ermelinda Santos-Silva, Niviann Blondet, Luis Bujanda, Uzma Shah, Richard J. Thompson, The Global ALagille Alliance (GALA) Study Group

University of Toronto
Fudan University
University of Pennsylvania
Children's Memorial Health Institute
Université Paris-Sud
Assistance publique – Hôpitaux de Paris
USC Ematologia, ASST PAPA GIOVANNI XXIII, Bergamo, Italy
Université catholique de Louvain
Stanford University
Yale University
Harvard University
Université Paris Cité
Karolinska Institutet
The Children's Hospital at Westmead
Emory University
University of Ulsan
Murdoch Children’s Research Institute, The Royal Children’s Hospital, Parkville, VIC, Australia
Mazumdar Shaw Medical Center
Starship Child Health
University of Utah
University of Colorado Department of Pediatrics
Leeds Teaching Hospitals NHS Trust
Hospital Italiano de Buenos Aires
University of Groningen
University of Malaya
University of Pittsburgh
Chris Hani Baragwanath Hospital
Mahidol University
Children’s Mercy Kansas City, Kansas City, MO, USA
University of Minnesota Twin Cities
Schneider Childrens Medical Center Israel
Koc University
Oregon Health and Science University
Hospital Universitari Vall d'Hebron
Institute of Liver and Biliary Sciences
University of Birmingham
Universidade de Brasília
Universidade Federal de Ciências da Saúde de Porto Alegre
Azienda Ospedaliero Universitaria Meyer
University of Nebraska Medical Center
Phoenix Children's Hospital
CPO Piedmont-AOU Citta della Salute e della Scienza, 10131 Turin, Italy
Istanbul University
Children's Medical Center Dallas
University of Tennessee Health Science Center
National and Kapodistrian University of Athens
Semmelweis University
Medical University of Silesia in Katowice
IRCCS Fondazione Ca'Granda – Ospedale Maggiore Policlinico - Milano
Hospital da Criança Conceição
University Medical Center Utrecht
Hospital de Cruces
Western University
Miami Transplant Institute
Rady Children's Hospital
University of the Witwatersrand
Aarhus University
University of Ottawa
University of Rochester
University of Ljubljana
University of Manitoba
University of Geneva
SJD Barcelona Children's Hospital
Johns Hopkins University
Ludwig Maximilian University of Munich
University Hospital Center of Santo António
University of Washington and Seattle Children’s Hospital, Seattle, WA, USA
Hospital Universitario Donostia
Massachusetts General Hospital
King's College London
Toronto Centre for Liver Disease, Toronto General Hospital, University Health Network, Toronto, Canada
Institute of Health Policy Management and Evaluation, University of Toronto, Toronto, Canada

Research output: Contribution to journal › Article › Academic › peer-review

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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.

Original language	English
Pages (from-to)	512-529
Journal	Hepatology
Volume	77
Issue number	2
DOIs	https://doi.org/10.1002/hep.32761
Publication status	Published - 1 Feb 2023
Externally published	Yes

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10.1002/hep.32761

Natural-history-of-liver-disease-in-a-large-international-cohort-of-children-with-alagille-syndrome.pdfFinal published version, 1.09 MBLicence: CC BY

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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. R., Spinner, N. B., Loomes, K. M., Piccoli, D. A., D'Antiga, L., Nicastro, E., Sokal, A., Demaret, T., Ebel, N. H., ... The Global ALagille Alliance (GALA) Study Group (2023). Natural history of liver disease in a large international cohort of children with Alagille syndrome: Results from the GALA study. Hepatology, 77(2), 512-529. https://doi.org/10.1002/hep.32761

@article{a22a757a98cc4704ab8c0a9ef04a52e2,

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

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.",

author = "Vandriel, \{Shannon M.\} and Li-Ting Li and Huiyu She and Jian-She Wang and Gilbert, \{Melissa A.\} and Irena Jankowska and Piotr Czubkowski and Dorota Gliwicz-Miedzi{\'n}ska and Gonzales, \{Emmanuel M.\} and Emmanuel Jacquemin and Bouligand, \{J. r{\^o}me\} and Spinner, \{Nancy B.\} and Loomes, \{Kathleen M.\} and Piccoli, \{David A.\} and Lorenzo D'Antiga and Emanuele Nicastro and Atienne Sokal and Tanguy Demaret and Ebel, \{Noelle H.\} and Feinstein, \{Jeffrey A.\} and Rima Fawaz and Silvia Nastasio and Florence Lacaille and Dominique Debray and Henrik Arnell and Bj{\"o}rn Fischler and Susan Siew and Michael Stormon and Karpen, \{Saul J.\} and Rene Romero and Kim, \{Kyung Mo\} and Baek, \{Woo Yim\} and Winita Hardikar and Sahana Shankar and Roberts, \{Amin J.\} and Evans, \{Helen M.\} and Jensen, \{M. Kyle\} and Marianne Kavan and Sundaram, \{Shikha S.\} and Alexander Chaidez and Palaniswamy Karthikeyan and Sanchez, \{Maria Camila\} and Cavalieri, \{Maria Lorena\} and Verkade, \{Henkjan J.\} and Lee, \{Way Seah\} and Squires, \{James E.\} and Christina Hajinicolaou and Chatmanee Lertudomphonwanit and Fischer, \{Ryan T.\} and Catherine Larson-Nath and Yael Mozer-Glassberg and Cigdem Arikan and Lin, \{Henry C.\} and Bernabeu, \{Jesus Quintero\} and Seema Alam and Kelly, \{Deirdre A.\} and Elisa Carvalho and Ferreira, \{Cristina Targa\} and Giuseppe Indolfi and Quiros-Tejeira, \{Ruben E.\} and Pinar Bulut and Calvo, \{Pier Luigi\} and Zerrin Anal and Valentino, \{Pamela L.\} and Desai, \{Dev M.\} and John Eshun and Maria Rogalidou and Antal Dezs{\H o}fi and Sabina Wiecek and Gabriella Nebbia and Pinto, \{Raquel Borges\} and Wolters, \{Victorien M.\} and Tamara, \{Mar{\'i}a Legarda\} and Zizzo, \{Andr{\'e}anne N.\} and Jennifer Garcia and Kathleen Schwarz and Marisa Beretta and Sandahl, \{Thomas Damgaard\} and Carolina Jimenez-Rivera and Nanda Kerkar and Jernej Brecelj and Quais Mujawar and Nathalie Rock and Busoms, \{Cristina Molera\} and Wikrom Karnsakul and Eberhard Lurz and Ermelinda Santos-Silva and Niviann Blondet and Luis Bujanda and Uzma Shah and Thompson, \{Richard J.\} and \{The Global ALagille Alliance (GALA) Study Group\} and Hansen, \{Bettina E.\} and Kamath, \{Binita M.\}",

year = "2023",

month = feb,

day = "1",

doi = "10.1002/hep.32761",

language = "English",

volume = "77",

pages = "512--529",

journal = "Hepatology",

issn = "0270-9139",

publisher = "John Wiley and Sons Ltd.",

number = "2",

}

Vandriel, SM, Li, L-T, She, H, Wang, J-S, Gilbert, MA, Jankowska, I, Czubkowski, P, Gliwicz-Miedzińska, D, Gonzales, EM, Jacquemin, E, Bouligand, JR, Spinner, NB, Loomes, KM, Piccoli, DA, D'Antiga, L, Nicastro, E, Sokal, A, Demaret, T, Ebel, NH, Feinstein, JA, Fawaz, R, Nastasio, S, Lacaille, F, Debray, D, Arnell, H, Fischler, B, Siew, S, Stormon, M, Karpen, SJ, Romero, R, Kim, KM, Baek, WY, Hardikar, W, Shankar, S, Roberts, AJ, Evans, HM, Jensen, MK, Kavan, M, Sundaram, SS, Chaidez, A, Karthikeyan, P, Sanchez, MC, Cavalieri, ML, Verkade, HJ, Lee, WS, Squires, JE, Hajinicolaou, C, Lertudomphonwanit, C, Fischer, RT, Larson-Nath, C, Mozer-Glassberg, Y, Arikan, C, Lin, HC, Bernabeu, JQ, Alam, S, Kelly, DA, Carvalho, E, Ferreira, CT, Indolfi, G, Quiros-Tejeira, RE, Bulut, P, Calvo, PL, Anal, Z, Valentino, PL, Desai, DM, Eshun, J, Rogalidou, M, Dezsőfi, A, Wiecek, S, Nebbia, G, Pinto, RB, Wolters, VM, Tamara, ML, Zizzo, AN, Garcia, J, Schwarz, K, Beretta, M, Sandahl, TD, Jimenez-Rivera, C, Kerkar, N, Brecelj, J, Mujawar, Q, Rock, N, Busoms, CM, Karnsakul, W, Lurz, E, Santos-Silva, E, Blondet, N, Bujanda, L, Shah, U, Thompson, RJ & The Global ALagille Alliance (GALA) Study Group 2023, 'Natural history of liver disease in a large international cohort of children with Alagille syndrome: Results from the GALA study', Hepatology, vol. 77, no. 2, pp. 512-529. https://doi.org/10.1002/hep.32761

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 - 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, J. rôme

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 - Larson-Nath, Catherine

AU - Mozer-Glassberg, Yael

AU - Arikan, Cigdem

AU - Lin, Henry C.

AU - Bernabeu, Jesus Quintero

AU - Alam, Seema

AU - Kelly, Deirdre A.

AU - Carvalho, Elisa

AU - Ferreira, Cristina Targa

AU - Indolfi, Giuseppe

AU - Quiros-Tejeira, Ruben E.

AU - Bulut, Pinar

AU - Calvo, Pier Luigi

AU - Anal, Zerrin

AU - Valentino, Pamela L.

AU - Desai, Dev M.

AU - Eshun, John

AU - Rogalidou, Maria

AU - Dezsőfi, Antal

AU - Wiecek, Sabina

AU - Nebbia, Gabriella

AU - Pinto, Raquel Borges

AU - Wolters, Victorien M.

AU - Tamara, María Legarda

AU - Zizzo, Andréanne N.

AU - Garcia, Jennifer

AU - Schwarz, Kathleen

AU - Beretta, Marisa

AU - Sandahl, Thomas Damgaard

AU - Jimenez-Rivera, Carolina

AU - Kerkar, Nanda

AU - Brecelj, Jernej

AU - Mujawar, Quais

AU - Rock, Nathalie

AU - Busoms, Cristina Molera

AU - Karnsakul, Wikrom

AU - Lurz, Eberhard

AU - Santos-Silva, Ermelinda

AU - Blondet, Niviann

AU - Bujanda, Luis

AU - Shah, Uzma

AU - Thompson, Richard J.

AU - The Global ALagille Alliance (GALA) Study Group

AU - Hansen, Bettina E.

AU - Kamath, Binita M.

PY - 2023/2/1

Y1 - 2023/2/1

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.

UR - https://www.scopus.com/pages/publications/85138168945

UR - https://www.ncbi.nlm.nih.gov/pubmed/36036223

U2 - 10.1002/hep.32761

DO - 10.1002/hep.32761

M3 - Article

C2 - 36036223

SN - 0270-9139

VL - 77

SP - 512

EP - 529

JO - Hepatology

JF - Hepatology

IS - 2

ER -

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

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