Benjamin L Shneider1, John C Magee2, Saul J Karpen3, Elizabeth B Rand4, Michael R Narkewicz5, Lee M Bass6, Kathleen Schwarz7, Peter F Whitington6, Jorge A Bezerra8, Nanda Kerkar9, Barbara Haber10, Philip Rosenthal11, Yumirle P Turmelle12, Jean P Molleston13, Karen F Murray14, Vicky L Ng15, Kasper S Wang16, Rene Romero17, Robert H Squires18, Ronen Arnon19, Averell H Sherker20, Jeffrey Moore21, Wen Ye21, Ronald J Sokol5. 1. Division of Pediatric Gastroenterology, Hepatology, and Nutrition, Department of Pediatrics, Baylor College of Medicine, Houston, TX. Electronic address: Benjamin.Shneider@bcm.edu. 2. University of Michigan Medical School, Ann Arbor, MI. 3. Division of Pediatric Gastroenterology, Hepatology, and Nutrition, Department of Pediatrics, Emory University School of Medicine/Children's Healthcare of Atlanta, Atlanta, GA. 4. Division of Gastroenterology, Hepatology, and Nutrition, Children's Hospital of Philadelphia, Philadelphia, PA. 5. Section of Pediatric Gastroenterology, Hepatology, and Nutrition, Department of Pediatrics, University of Colorado School of Medicine, Children's Hospital Colorado, Aurora, CO. 6. Pediatrics Division of Gastroenterology, Hepatology, and Nutrition, Ann and Robert H. Lurie Children's Hospital of Chicago, Chicago, IL. 7. Johns Hopkins School of Medicine, Baltimore, MD. 8. Division of Pediatric Gastroenterology, Hepatology, and Nutrition, Cincinnati Children's Hospital Medical Center, Cincinnati, OH. 9. Division of Gastroenterology, Hepatology and Nutrition, Children's Hospital of Los Angeles, University of Southern California, Los Angeles, CA. 10. Merck Sharp and Dohme Corp, Merck Research Laboratories, North Wales, PA. 11. Division of Gastroenterology, Hepatology, and Nutrition, Department of Pediatrics, University of California, San Francisco Benioff Children's Hospital, San Francisco, CA. 12. Washington University School of Medicine, St. Louis, MO. 13. Department of Pediatrics, Division of Pediatric Gastroenterology, Hepatology, and Nutrition, Indiana University School of Medicine, Indianapolis, IN. 14. Division of Gastroenterology and Hepatology, Department of Pediatrics, University of Washington and Seattle Children's, Seattle, WA. 15. The Hospital for Sick Children, Toronto, Ontario, Canada. 16. Division of Pediatric Surgery, Children's Hospital, Los Angeles, CA. 17. Division of Pediatric Gastroenterology, Hepatology, and Nutrition, Department of Pediatrics, Emory University, Atlanta, GA. 18. Children's Hospital of Pittsburgh, Pittsburgh, PA. 19. Division of Pediatric Gastroenterology, Hepatology, and Nutrition, Mount Sinai Medical Center, New York, NY. 20. Liver Diseases Research Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD. 21. Department of Biostatistics, University of Michigan, Ann Arbor, MI.
Abstract
OBJECTIVES: To prospectively assess the value of serum total bilirubin (TB) within 3 months of hepatoportoenterostomy (HPE) in infants with biliary atresia as a biomarker predictive of clinical sequelae of liver disease in the first 2 years of life. STUDY DESIGN: Infants with biliary atresia undergoing HPE between June 2004 and January 2011 were enrolled in a prospective, multicenter study. Complications were monitored until 2 years of age or the earliest of liver transplantation (LT), death, or study withdrawal. TB below 2 mg/dL (34.2 μM) at any time in the first 3 months (TB <2.0, all others TB ≥ 2) after HPE was examined as a biomarker, using Kaplan-Meier survival and logistic regression. RESULTS: Fifty percent (68/137) of infants had TB < 2.0 in the first 3 months after HPE. Transplant-free survival at 2 years was significantly higher in the TB < 2.0 group vs TB ≥ 2 (86% vs 20%, P < .0001). Infants with TB ≥ 2 had diminished weight gain (P < .0001), greater probability of developing ascites (OR 6.4, 95% CI 2.9-14.1, P < .0001), hypoalbuminemia (OR 7.6, 95% CI 3.2-17.7, P < .0001), coagulopathy (OR 10.8, 95% CI 3.1-38.2, P = .0002), LT (OR 12.4, 95% CI 5.3-28.7, P < .0001), or LT or death (OR 16.8, 95% CI 7.2-39.2, P < .0001). CONCLUSIONS: Infants whose TB does not fall below 2.0 mg/dL within 3 months of HPE were at high risk for early disease progression, suggesting they should be considered for LT in a timely fashion. Interventions increasing the likelihood of achieving TB <2.0 mg/dL within 3 months of HPE may enhance early outcomes. TRIAL REGISTRATION: ClinicalTrials.gov: NCT00061828 and NCT00294684.
OBJECTIVES: To prospectively assess the value of serum total bilirubin (TB) within 3 months of hepatoportoenterostomy (HPE) in infants with biliary atresia as a biomarker predictive of clinical sequelae of liver disease in the first 2 years of life. STUDY DESIGN:Infants with biliary atresia undergoing HPE between June 2004 and January 2011 were enrolled in a prospective, multicenter study. Complications were monitored until 2 years of age or the earliest of liver transplantation (LT), death, or study withdrawal. TB below 2 mg/dL (34.2 μM) at any time in the first 3 months (TB <2.0, all others TB ≥ 2) after HPE was examined as a biomarker, using Kaplan-Meier survival and logistic regression. RESULTS: Fifty percent (68/137) of infants had TB < 2.0 in the first 3 months after HPE. Transplant-free survival at 2 years was significantly higher in the TB < 2.0 group vs TB ≥ 2 (86% vs 20%, P < .0001). Infants with TB ≥ 2 had diminished weight gain (P < .0001), greater probability of developing ascites (OR 6.4, 95% CI 2.9-14.1, P < .0001), hypoalbuminemia (OR 7.6, 95% CI 3.2-17.7, P < .0001), coagulopathy (OR 10.8, 95% CI 3.1-38.2, P = .0002), LT (OR 12.4, 95% CI 5.3-28.7, P < .0001), or LT or death (OR 16.8, 95% CI 7.2-39.2, P < .0001). CONCLUSIONS:Infants whose TB does not fall below 2.0 mg/dL within 3 months of HPE were at high risk for early disease progression, suggesting they should be considered for LT in a timely fashion. Interventions increasing the likelihood of achieving TB <2.0 mg/dL within 3 months of HPE may enhance early outcomes. TRIAL REGISTRATION: ClinicalTrials.gov: NCT00061828 and NCT00294684.
Authors: Benjamin L Shneider; Morton B Brown; Barbara Haber; Peter F Whitington; Kathleen Schwarz; Robert Squires; Jorge Bezerra; Ross Shepherd; Philip Rosenthal; Jay H Hoofnagle; Ronald J Sokol Journal: J Pediatr Date: 2006-04 Impact factor: 4.406
Authors: Patricia A DeRusso; Wen Ye; Ross Shepherd; Barbara A Haber; Benjamin L Shneider; Peter F Whitington; Kathleen B Schwarz; Jorge A Bezerra; Philip Rosenthal; Saul Karpen; Robert H Squires; John C Magee; Patricia R Robuck; Ronald J Sokol Journal: Hepatology Date: 2007-11 Impact factor: 17.425
Authors: Ronald J Sokol; Ross W Shepherd; Riccardo Superina; Jorge A Bezerra; Patricia Robuck; Jay H Hoofnagle Journal: Hepatology Date: 2007-08 Impact factor: 17.425
Authors: Vicky L Ng; Lisa G Sorensen; Estella M Alonso; Emily M Fredericks; Wen Ye; Jeff Moore; Saul J Karpen; Benjamin L Shneider; Jean P Molleston; Jorge A Bezerra; Karen F Murray; Kathleen M Loomes; Philip Rosenthal; Robert H Squires; Kasper Wang; Ronen Arnon; Kathleen B Schwarz; Yumirle P Turmelle; Barbara H Haber; Averell H Sherker; John C Magee; Ronald J Sokol Journal: J Pediatr Date: 2018-03-05 Impact factor: 4.406
Authors: Lee M Bass; Benjamin L Shneider; Lisa Henn; Nathan P Goodrich; John C Magee Journal: J Pediatr Gastroenterol Nutr Date: 2019-06 Impact factor: 2.839
Authors: Jessica A Zagory; Michael Fenlon; William Dietz; Menghan Zhao; Marie V Nguyen; Pavin Trinh; Maeva Adoumie; Alex Park; Jiabo Xu; Elaa Mahdi; Alison Glazier; Nicolas Malkoff; Nirmala Mavila; Kasper S Wang Journal: Hepatology Date: 2019-04-11 Impact factor: 17.425
Authors: Tea Soini; Marjut Pihlajoki; Noora Andersson; Jouko Lohi; Kari A Huppert; David A Rudnick; Stacey S Huppert; David B Wilson; Mikko P Pakarinen; Markku Heikinheimo Journal: Am J Physiol Gastrointest Liver Physiol Date: 2018-02-01 Impact factor: 4.052
Authors: Jorge A Bezerra; Rebecca G Wells; Cara L Mack; Saul J Karpen; Jay H Hoofnagle; Edward Doo; Ronald J Sokol Journal: Hepatology Date: 2018-09 Impact factor: 17.425
Authors: Sanjiv Harpavat; Joseph A Garcia-Prats; Carlos Anaya; Mary L Brandt; Philip J Lupo; Milton J Finegold; Alice Obuobi; Adel A ElHennawy; William S Jarriel; Benjamin L Shneider Journal: JAMA Date: 2020-03-24 Impact factor: 56.272