Assessing the Validity of Adult‐derived Prognostic Models for Primary Sclerosing Cholangitis Outcomes in Children

ABSTRACT Background: Natural history models for primary sclerosing cholangitis (PSC) are derived from adult patient data, but have never been validated in children. It is unclear how accurate such models are for children with PSC. Methods: We utilized the pediatric PSC consortium database to assess...

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Published inJournal of pediatric gastroenterology and nutrition Vol. 70; no. 1; pp. e12 - e17
Main Authors Deneau, Mark R., Valentino, Pamela L., Mack, Cara, Alqoaer, Khaled, Amin, Mansi, Amir, Achiya Z., Aumar, Madeleine, Auth, Marcus, Broderick, Annemarie, DiGuglielmo, Matthew, Draijer, Laura G., El‐Matary, Wael, Ferrari, Federica, Furuya, Katryn N., Gottrand, Frederic, Gupta, Nitika, Homan, Matjaz, Jensen, M.K., Kamath, Binita M., Kim, Kyung Mo, Kolho, Kaija‐Leena, Koot, Bart, Iorio, Raffaele, Martinez, Mercedes, Miloh, Tamir, Mohan, Parvathi, Palle, Sirish, Papadopoulou, Alexandra, Ricciuto, Amanda, Saubermann, Lawrence, Sathya, Pushpa, Shteyer, Eyal, Smolka, Vratislav, Tanaka, Atsushi, Varier, Raghu, Venkat, Veena, Vitola, Bernadette, Woynarowski, Marek, Guthery, Stephen
Format Journal Article
LanguageEnglish
Published United States by European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition 01.01.2020
by European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology
Lippincott, Williams & Wilkins
SeriesJournal of Pediatric Gastroenterology and Nutrition
Subjects
Child
Cholangitis, Sclerosing - complications
Cholangitis, Sclerosing - mortality
Female
Gastroenterology - methods
Hepatitis, Autoimmune - complications
Hepatitis, Autoimmune - mortality
Humans
Kaplan-Meier Estimate
Life Sciences
Liver Function Tests - methods
Male
Models, Statistical
natural history
pediatric
Pediatrics - methods
Predictive Value of Tests
primary sclerosing cholangitis
Prognosis
Reproducibility of Results
Risk Assessment - methods
risk stratification
risk stratification
prognosis
natural history
primary sclerosing cholangitis
pediatric
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Abstract ABSTRACT Background: Natural history models for primary sclerosing cholangitis (PSC) are derived from adult patient data, but have never been validated in children. It is unclear how accurate such models are for children with PSC. Methods: We utilized the pediatric PSC consortium database to assess the Revised Mayo Clinic, Amsterdam‐Oxford, and Boberg models. We calculated the risk stratum and predicted survival for each patient within each model using patient data at PSC diagnosis, and compared it with observed survival. We evaluated model fit using the c‐statistic. Results: Model fit was good at 1 year (c‐statistics 0.93, 0.87, 0.82) and fair at 10 years (0.78, 0.75, 0.69) in the Mayo, Boberg, and Amsterdam‐Oxford models, respectively. The Mayo model correctly classified most children as low risk, whereas the Amsterdam‐Oxford model incorrectly classified most as high risk. All of the models underestimated survival of patients classified as high risk. Albumin, bilirubin, AST, and platelets were most associated with outcomes. Autoimmune hepatitis was more prevalent in higher risk groups, and over‐weighting of AST in these patients accounted for the observed versus predicted survival discrepancy. Conclusions: All 3 models offered good short‐term discrimination of outcomes but only fair long‐term discrimination. None of the models account for the high prevalence of features of autoimmune hepatitis overlap in children and the associated elevated aminotransferases. A pediatric‐specific model is needed. AST, bilirubin, albumin, and platelets will be important predictors, but must be weighted to account for the unique features of PSC in children.
AbstractList BACKGROUND:Natural history models for primary sclerosing cholangitis (PSC) are derived from adult patient data, but have never been validated in children. It is unclear how accurate such models are for children with PSC. METHODS:We utilized the pediatric PSC consortium database to assess the Revised Mayo Clinic, Amsterdam-Oxford, and Boberg models. We calculated the risk stratum and predicted survival for each patient within each model using patient data at PSC diagnosis, and compared it with observed survival. We evaluated model fit using the c-statistic. RESULTS:Model fit was good at 1 year (c-statistics 0.93, 0.87, 0.82) and fair at 10 years (0.78, 0.75, 0.69) in the Mayo, Boberg, and Amsterdam-Oxford models, respectively. The Mayo model correctly classified most children as low risk, whereas the Amsterdam-Oxford model incorrectly classified most as high risk. All of the models underestimated survival of patients classified as high risk. Albumin, bilirubin, AST, and platelets were most associated with outcomes. Autoimmune hepatitis was more prevalent in higher risk groups, and over-weighting of AST in these patients accounted for the observed versus predicted survival discrepancy. CONCLUSIONS:All 3 models offered good short-term discrimination of outcomes but only fair long-term discrimination. None of the models account for the high prevalence of features of autoimmune hepatitis overlap in children and the associated elevated aminotransferases. A pediatric-specific model is needed. AST, bilirubin, albumin, and platelets will be important predictors, but must be weighted to account for the unique features of PSC in children.
ABSTRACT Background: Natural history models for primary sclerosing cholangitis (PSC) are derived from adult patient data, but have never been validated in children. It is unclear how accurate such models are for children with PSC. Methods: We utilized the pediatric PSC consortium database to assess the Revised Mayo Clinic, Amsterdam‐Oxford, and Boberg models. We calculated the risk stratum and predicted survival for each patient within each model using patient data at PSC diagnosis, and compared it with observed survival. We evaluated model fit using the c‐statistic. Results: Model fit was good at 1 year (c‐statistics 0.93, 0.87, 0.82) and fair at 10 years (0.78, 0.75, 0.69) in the Mayo, Boberg, and Amsterdam‐Oxford models, respectively. The Mayo model correctly classified most children as low risk, whereas the Amsterdam‐Oxford model incorrectly classified most as high risk. All of the models underestimated survival of patients classified as high risk. Albumin, bilirubin, AST, and platelets were most associated with outcomes. Autoimmune hepatitis was more prevalent in higher risk groups, and over‐weighting of AST in these patients accounted for the observed versus predicted survival discrepancy. Conclusions: All 3 models offered good short‐term discrimination of outcomes but only fair long‐term discrimination. None of the models account for the high prevalence of features of autoimmune hepatitis overlap in children and the associated elevated aminotransferases. A pediatric‐specific model is needed. AST, bilirubin, albumin, and platelets will be important predictors, but must be weighted to account for the unique features of PSC in children.
Natural history models for primary sclerosing cholangitis (PSC) are derived from adult patient data, but have never been validated in children. It is unclear how accurate such models are for children with PSC.We utilized the pediatric PSC consortium database to assess the Revised Mayo Clinic, Amsterdam-Oxford, and Boberg models. We calculated the risk stratum and predicted survival for each patient within each model using patient data at PSC diagnosis, and compared it with observed survival. We evaluated model fit using the c-statistic.Model fit was good at 1 year (c-statistics 0.93, 0.87, 0.82) and fair at 10 years (0.78, 0.75, 0.69) in the Mayo, Boberg, and Amsterdam-Oxford models, respectively. The Mayo model correctly classified most children as low risk, whereas the Amsterdam-Oxford model incorrectly classified most as high risk. All of the models underestimated survival of patients classified as high risk. Albumin, bilirubin, AST, and platelets were most associated with outcomes. Autoimmune hepatitis was more prevalent in higher risk groups, and over-weighting of AST in these patients accounted for the observed versus predicted survival discrepancy.All 3 models offered good short-term discrimination of outcomes but only fair long-term discrimination. None of the models account for the high prevalence of features of autoimmune hepatitis overlap in children and the associated elevated aminotransferases. A pediatric-specific model is needed. AST, bilirubin, albumin, and platelets will be important predictors, but must be weighted to account for the unique features of PSC in children.
BACKGROUNDNatural history models for primary sclerosing cholangitis (PSC) are derived from adult patient data, but have never been validated in children. It is unclear how accurate such models are for children with PSC. METHODSWe utilized the pediatric PSC consortium database to assess the Revised Mayo Clinic, Amsterdam-Oxford, and Boberg models. We calculated the risk stratum and predicted survival for each patient within each model using patient data at PSC diagnosis, and compared it with observed survival. We evaluated model fit using the c-statistic. RESULTSModel fit was good at 1 year (c-statistics 0.93, 0.87, 0.82) and fair at 10 years (0.78, 0.75, 0.69) in the Mayo, Boberg, and Amsterdam-Oxford models, respectively. The Mayo model correctly classified most children as low risk, whereas the Amsterdam-Oxford model incorrectly classified most as high risk. All of the models underestimated survival of patients classified as high risk. Albumin, bilirubin, AST, and platelets were most associated with outcomes. Autoimmune hepatitis was more prevalent in higher risk groups, and over-weighting of AST in these patients accounted for the observed versus predicted survival discrepancy. CONCLUSIONSAll 3 models offered good short-term discrimination of outcomes but only fair long-term discrimination. None of the models account for the high prevalence of features of autoimmune hepatitis overlap in children and the associated elevated aminotransferases. A pediatric-specific model is needed. AST, bilirubin, albumin, and platelets will be important predictors, but must be weighted to account for the unique features of PSC in children.
Natural history models for primary sclerosing cholangitis (PSC) are derived from adult patient data, but have never been validated in children. It is unclear how accurate such models are for children with PSC. We utilized the pediatric PSC consortium database to assess the Revised Mayo Clinic, Amsterdam-Oxford, and Boberg models. We calculated the risk stratum and predicted survival for each patient within each model using patient data at PSC diagnosis, and compared it with observed survival. We evaluated model fit using the c-statistic. Model fit was good at 1 year (c-statistics 0.93, 0.87, 0.82) and fair at 10 years (0.78, 0.75, 0.69) in the Mayo, Boberg, and Amsterdam-Oxford models, respectively. The Mayo model correctly classified most children as low risk, whereas the Amsterdam-Oxford model incorrectly classified most as high risk. All of the models underestimated survival of patients classified as high risk. Albumin, bilirubin, AST, and platelets were most associated with outcomes. Autoimmune hepatitis was more prevalent in higher risk groups, and over-weighting of AST in these patients accounted for the observed versus predicted survival discrepancy. All 3 models offered good short-term discrimination of outcomes but only fair long-term discrimination. None of the models account for the high prevalence of features of autoimmune hepatitis overlap in children and the associated elevated aminotransferases. A pediatric-specific model is needed. AST, bilirubin, albumin, and platelets will be important predictors, but must be weighted to account for the unique features of PSC in children.
Author Vitola, Bernadette
Valentino, Pamela L.
Homan, Matjaz
Ferrari, Federica
Papadopoulou, Alexandra
Amin, Mansi
DiGuglielmo, Matthew
El‐Matary, Wael
Iorio, Raffaele
Miloh, Tamir
Furuya, Katryn N.
Ricciuto, Amanda
Guthery, Stephen
Alqoaer, Khaled
Shteyer, Eyal
Woynarowski, Marek
Auth, Marcus
Kim, Kyung Mo
Saubermann, Lawrence
Jensen, M.K.
Kolho, Kaija‐Leena
Koot, Bart
Deneau, Mark R.
Martinez, Mercedes
Mohan, Parvathi
Smolka, Vratislav
Varier, Raghu
Broderick, Annemarie
Kamath, Binita M.
Mack, Cara
Gupta, Nitika
Gottrand, Frederic
Sathya, Pushpa
Venkat, Veena
Draijer, Laura G.
Palle, Sirish
Amir, Achiya Z.
Aumar, Madeleine
Tanaka, Atsushi
AuthorAffiliation Lille University Hospital of Lille, Lille, France
Nemours Alfred I duPont Hospital For Children, Wilmington, DE
Phoenix Children's Hospital, Phoenix, AZ
Emory University School of Medicine, Atlanta, GA
University of Manitoba, Winnipeg, Manitoba, Canada
Mayo Clinic, Rochester, MN
University of Ulsan, Seoul, South Korea
Memorial University, St. John's, Newfoundland and Labrador, Canada
Sapienza University of Rome, Rome, Italy
Columbia University College of Physicians and Surgeons, New York, NY
Northwest Pediatric Gastroenterology LLC, Portland, OR
Children's Health Memorial Institute, Warsaw, Poland
University of Helsinki, Helsinki, Finland
The Dana-Dwek Children's Hospital, The Tel-Aviv Medical Center, Tel-Aviv University, Tel Aviv, Israel
University of Pittsburgh Medical Center, Pittsburgh, PA
University of Ljubljana, Ljubljana, Slovenia
University of Athens, Athens, Greece
University of Colorado School of Medicine, Aurora, CO
Children's National Medical Center, Washington, DC
Palacky University, Olomouc
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CitedBy_id crossref_primary_10_1016_j_cld_2022_03_009
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ContentType Journal Article
Copyright 2020 by European Society for European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition
by European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition
2020 by European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology
Distributed under a Creative Commons Attribution 4.0 International License
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– notice: 2020 by European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology
– notice: Distributed under a Creative Commons Attribution 4.0 International License
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Issue 1
Keywords risk stratification
prognosis
natural history
primary sclerosing cholangitis
pediatric
Language English
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Notes Supplemental digital content is available for this article. Direct URL citations appear in the printed text, and links to the digital files are provided in the HTML text of this article on the journal's Web site
Research reported in this publication was supported by PSC Partners Seeking A Cure, the Primary Children's Hospital Foundation, the National Center for Advancing Translational Sciences of the National Institutes of Health under Award Numbers KL2TR001065 and 8UL1TR000105 (formerly UL1RR025764). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health
www.jpgn.org
.
M.D. has consulted for HighTide Biopharmaceuticals LLC. B.K. is a consultant for Retrophin. T.M. consults, advises, and is on the speaker board for Alexion. P.M. received grants from Gilead.
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Snippet ABSTRACT Background: Natural history models for primary sclerosing cholangitis (PSC) are derived from adult patient data, but have never been validated in...
BACKGROUND:Natural history models for primary sclerosing cholangitis (PSC) are derived from adult patient data, but have never been validated in children. It...
Natural history models for primary sclerosing cholangitis (PSC) are derived from adult patient data, but have never been validated in children. It is unclear...
BACKGROUNDNatural history models for primary sclerosing cholangitis (PSC) are derived from adult patient data, but have never been validated in children. It is...
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SubjectTerms Child
Cholangitis, Sclerosing - complications
Cholangitis, Sclerosing - mortality
Female
Gastroenterology - methods
Hepatitis, Autoimmune - complications
Hepatitis, Autoimmune - mortality
Humans
Kaplan-Meier Estimate
Life Sciences
Liver Function Tests - methods
Male
Models, Statistical
natural history
pediatric
Pediatrics - methods
Predictive Value of Tests
primary sclerosing cholangitis
Prognosis
Reproducibility of Results
Risk Assessment - methods
risk stratification
Title Assessing the Validity of Adult‐derived Prognostic Models for Primary Sclerosing Cholangitis Outcomes in Children
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