Modeling Outcomes in Children With Biliary Atresia With Native Liver After 2 Years of Age

• Type of Material: Article
• Authors: Veena Venkat, UPMC Children's Hospital of Pittsburgh; Vicky L. Ng, University of Toronto; John C. Magee, University of Michigan Hospitals and Health Centers; Wen Ye, University of Michigan Hospitals and Health Centers; Kieran Hawthorne, Arbor Research Collaborative for Health; Sanjiv Harpavat, Texas Children's Hospital, Liver Center; Jean P. Molleston, Indiana University‐Riley Hospital for Children; Karen F. Murray, Cleveland Clinic Children’s; Kasper S. Wang, Children's Hospital Los Angeles; Nisreen Soufi, Children's Hospital Los Angeles; Lee M. Bass, Ann & Robert H. Lurie Children's Hospital of Chicago; Estella M. Alonso, Ann & Robert H. Lurie Children's Hospital of Chicago; Jorge A. Bezerra, Cincinnati Children's Hospital Medical Center; M. Kyle Jensen, University of Utah; Binita M. Kamath, University of Toronto; Kathleen M. Loomes, Childrens Hospital of Philadelphia; Cara L. Mack, University of Colorado School of Medicine; Philip Rosenthal, University of California, San Francisco; Benjamin L. Shneider, Texas Children's Hospital; Robert H. Squires, UPMC Children's Hospital of Pittsburgh; Ronald J. Sokol, University of Colorado School of Medicine; Saul Karpen, Emory University
• Language: English
• Date: 2020-10-03
• Publisher: JOHN WILEY & SONS LTD
• Publication Version: Final Published Version
• Copyright Statement: © 2020 The Authors.
• License: Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1002/hep4.1602
• Title of Journal or Parent Work: HEPATOLOGY COMMUNICATIONS
• Volume: 4
• Issue: 12
• Start Page: 1824
• End Page: 1834
• Grant/Funding Information: Supported by the National Institute of Diabetes, Digestive, and Kidney Diseases U01 grants (DK062445 to Mt. Sinai School of Medicine, DK062497 to Cincinnati Children’s Hospital Medical Center, DK062470 to Children’s Healthcare of Atlanta, DK062481 to The Children’s Hospital of Philadelphia, DK062456 to University of Michigan, DK084536 to Riley Hospital for Children, DK084575 to Seattle Children’s Hospital, DK062500 to University of California San Francisco [UCSF] Children’s Hospital, DK062466 to Children’s Hospital of Pittsburgh of the University of Pittsburgh Medical Center [UPMC], DK062453 to Children’s Hospital Colorado, DK084538 to Children’s Hospital Los Angeles, DK062436 to Ann & Robert H Lurie Children’s Hospital of Chicago, DK103149 to Texas Children’s Hospital, DK103135 to The Hospital for Sick Children, DK103140 to University of Utah), the National Institutes of Health, National Center for Advancing Translational Sciences, Clinical and Translational Sciences Awards (UL1 TR002535 to University of Colorado, UL1 TR001872 to UCSF Children’s Hospital, UL1 TR001857 to Children’s Hospital of Pittsburgh of UPMC, UL1 TR001878 to The Children’s Hospital of Philadelphia, UL1 TR000423 and UL1 RR025014 to Seattle Children’s Hospital, UL1TR002378 to Children’s Healthcare of Atlanta, UL1TR00130 to Children’s Hospital of Los Angeles).
• Keywords: PORTOENTEROSTOMY; ESOPHAGEAL-VARICES; SURVIVAL; Gastroenterology & Hepatology; LONG-TERM; Life Sciences & Biomedicine; PREDICTION RULE; TRANSPLANTATION; MULTICENTER; MANAGEMENT; Science & Technology; HEPATOPORTOENTEROSTOMY; BILIRUBIN
• Research Categories: Health Sciences, Medicine and Surgery; Engineering, Biomedical

Abstract

Approximately 50% of infants with biliary atresia (BA) undergoing Kasai portoenterostomy show survival with native liver (SNL) at age 2 years. Predictors of disease progression after age 2 years are unknown, despite estimates of 20%-30% undergoing liver transplant (LT) between age 2 and 18 years. We sought to address this knowledge gap by developing prognostic models in participants of the multicenter prospective National Institutes of Health-supported Childhood Liver Disease Research Network. We extracted 14 clinical and biochemical variables at age 2 years to develop two models for future outcomes: 1) LT or death (LTD) and 2) first sentinel event (SE), either new onset ascites, hepatopulmonary syndrome (HPS), or gastrointestinal (GI) bleed. A total of 240 participants, enrolled between 2004 and 2017, were followed until a median age of 5.1 years (range, 2.0-13.3 years). Of these participants, 38 underwent LT (n = 37) or death (n = 1); cumulative incidence, 23.7% (95% confidence interval [CI], 16.2%-32.0%). Twenty-seven experienced either new-onset ascites (n = 13), HPS (n = 1), or GI bleed (n = 14). One participant had ascites and GI bleed concurrently; cumulative incidence, 21.5% (95% CI, 14.2%-29.8%) by age 10 years. The Cox proportional hazard model predicted risk of LTD, using total bilirubin, albumin, platelet count, and history of either ascites or cholangitis (BA LTD model), with a C-index of 0.88 (range, 0.86-0.89). A cause-specific hazard competing risk model predicted SE using platelet count and gamma glutamyltransferase levels (BA SE model) with a C-index of 0.81 (range, 0.80-0.84). Internal model validity was assessed using Harrell’s C-index with cross-validation. Conclusion: Stratification using these models identified risk of poor outcomes in patients with BA SNL after age 2 years. The models may identify those who would benefit from enhanced clinical surveillance and prioritization in clinical trials.