title: A national retrospective study of paediatric end-stage liver disease as a predictor of change to second-line therapy in children with autoimmune hepatitis.
abstract: Adult studies of autoimmune hepatitis (AIH) have shown that the model of end-stage liver disease is associated with resistance to first-line treatment. Using a multicentre retrospective database, we sought to determine if the paediatric end-stage liver disease (PELD) score would similarly predict treatment resistance in paediatric AIH.
  
  
  
  One hundred and seventy-one children from 13 Canadian centres who fulfilled the International Autoimmune Hepatitis Group (IAIHG) criteria were included and assessed for change to second-line therapy within 24 months of primary treatment onset. Those with PSC overlap at presentation, or missing data on the PELD variables were excluded. PELD was calculated for all remaining patients. Univariate analysis and receiver-operator characteristic (ROC) curves were performed to determine the predictive ability of the PELD score to change to second-line therapy.
  
  
  
  A total of 103 children were included with median age of 11 years (range 2-17). Mean PELD was -2.51±8.58. Second-line therapy was used within 24 months of diagnosis in 13 patients. Univariate analysis revealed that change to second-line therapy was associated with higher PELD (P=.028) and internal normalized ratio (INR) (P=.011). ROC curves for PELD and its individual components were performed. The strength of association was strongest with INR (AUC 0.72; CI: 0.58-0.86) although the composite PELD score also showed some predictive ability (AUC 0.67; CI: 0.52-0.81).
  
  
  
  In this paediatric AIH cohort, higher PELD at presentation predicted change to second-line therapy within the first 2 years of follow-up. INR appeared to be the main contributor to that association.
authors.affiliation: Division of Gastroenterology, Department of Paediatrics, London Children's Hospital, Western University, London, ON, Canada.
authors.forename: Andréanne N
authors.identifier: 0000-0001-6350-2057
authors.initials: AN
authors.lastname: Zizzo
authors.affiliation: Division of Gastroenterology, Hepatology and Nutrition, Department of Paediatrics, Children's Hospital of Eastern Ontario, University of Ottawa, Ottawa, ON, Canada.
authors.forename: Carolina
authors.initials: C
authors.lastname: Jimenez-Rivera
authors.affiliation: Department of Medicine, University Health Network, University of Toronto,  Toronto, ON, Canada.
authors.forename: Joseph
authors.initials: J
authors.lastname: Kim
authors.affiliation: Division of Paediatric Gastroenterology, Hepatology and Nutrition, Department of Paediatrics, University of British Columbia, Vancouver, BC, Canada.|Child and Family Research Institute, Vancouver, BC, Canada.
authors.forename: Richard A
authors.initials: RA
authors.lastname: Schreiber
authors.affiliation: Division of Gastroenterology, Hepatology and Nutrition, The Hospital for Sick Children, Toronto, ON, Canada.|Department of Paediatrics, University of Toronto, Toronto, ON, Canada.
authors.forename: Simon C
authors.initials: SC
authors.lastname: Ling
authors.affiliation: Division of Paediatric Gastroenterology and Nutrition, Department of Paediatrics, University of Alberta, Edmonton, AB, Canada.
authors.forename: Jason
authors.initials: J
authors.lastname: Yap
authors.affiliation: Department of Paediatrics, Faculty of Medicine, Memorial University, St. John's, NL, Canada.
authors.forename: Jeff
authors.initials: J
authors.lastname: Critch
authors.affiliation: Division of Paediatric Gastroenterology and Nutrition, Montreal Children's Hospital, McGill University, Montreal, QC, Canada.
authors.forename: Najma
authors.initials: N
authors.lastname: Ahmed
authors.affiliation: Division of Gastroenterology, Hepatology and Nutrition, Department of Paediatrics, Hôpital Sainte-Justine, Université de Montréal, Montreal, QC, Canada.
authors.forename: Fernando
authors.initials: F
authors.lastname: Alvarez
authors.affiliation: Division of Gastroenterology, Hepatology and Nutrition, The Hospital for Sick Children, Toronto, ON, Canada.|Department of Paediatrics, University of Toronto, Toronto, ON, Canada.
authors.forename: Binita M
authors.initials: BM
authors.lastname: Kamath
mesh_terms: D000293:Adolescent; D000305:Adrenal Cortex Hormones / Q000627:therapeutic use; D000367:Age Factors; D019540:Area Under Curve; D001379:Azathioprine / Q000627:therapeutic use; D002170:Canada; D002648:Child; D002675:Child, Preschool; D016208:Databases, Factual; D003661:Decision Support Techniques; D057915:Drug Substitution; D005260:Female; D019693:Hepatitis, Autoimmune / Q000097:blood / Q000175:diagnosis* / Q000188:drug therapy*; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects / Q000627:therapeutic use*; D019934:International Normalized Ratio; D008297:Male; D011237:Predictive Value of Tests; D012372:ROC Curve; D012189:Retrospective Studies; D012307:Risk Factors; D013997:Time Factors; D017211:Treatment Failure
chemical_list: D000305:Adrenal Cortex Hormones; D007166:Immunosuppressive Agents; D001379:Azathioprine
keywords: autoimmune liver disease; paediatric; paediatric end-stage liver disease score; second-line therapy