Gamma Glutamyltransferase Reduction Is Associated With Favorable Outcomes in Pediatric Primary Sclerosing Cholangitis.

• Type of Material: Article
• Authors: Mark R. Deneau, University of Utah; Cara Mack, University of Colorado; Reham Abdou, Nassau University; Mansi Amin, Phoenix Children's Hospital; Achiya Amir, Dana-Dwek Children's Hospital; Marcus Auth, Alder Hey Children's Hospital; Fateh Bazerbachi, Mayo Clinic; Anne Marie Broderick, University College Dublin; Albert Chan, University of Rochester; Matthew DiGuglielmo, Nemours Alfred I duPont Hospital For Children; Wael El-Matary, University of Manitoba; Mounif El-Youssef, Mayo Clinic; Federica Ferrari, Sapienza University of Rome; Katryn N. Furuya, Mayo Clinic; Frederic Gottrand, Lille University Hospital of Lille; Nitika Gupta, Emory University; Matjaz Homan, University of Ljubljana; M.K. Jensen, University of Utah; Binita M. Kamath, University of Toronto; Kyung Mo Kim, University of Ulsan; Kaija-Leena Kolho, University of Helsinki; Anastasia Konidari, University of Liverpool; Bart Koot, Academic Medical Centre; Raffaele Iorio, University of Naples Federico II; Mercedes Martinez, Columbia University; Parvathi Mohan, Children's National Medical Center; Sirish Palle, Emory University; Alexandra Papadopoulou, University of Athens; Amanda Ricciuto, University of Toronto; Lawrence Saubermann, University of Rochester; Pushpa Sathya, Memorial University St. John's; Eyal Shteyer, Shaare Zedek Medical Center; Vratislav Smolka, Palacky University; Atsushi Tanaka, Teikyo University School of Medicine; Pamela L. Valentino, Yale University; Raghu Varier, Northwest Pediatric Gastroenterology LLC; Veena Venkat, University of Pittsburgh; Bernadette Vitola, Medical College of Wisconsin; Miriam Vos, Emory University; Marek Woynarowski, Children's Health Memorial Institute; Jason Yap, University of Alberta; Tamir Miloh, Phoenix Children's Hospital
• Language: English
• Date: 2018-11
• Publisher: Wiley Open Access: Creative Commons Attribution Non-Commercial No Derivatives
• Publication Version: Final Published Version
• Copyright Statement: © 2018 The Authors. Hepatology Communications published by Wiley Periodicals, Inc., on behalf of the American Association for the Study of Liver Diseases.
• License: Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1002/hep4.1251
• Title of Journal or Parent Work: Hepatology Communications
• ISSN: 2471-254X
• Volume: 2
• Issue: 11
• Start Page: 1369
• End Page: 1378
• Grant/Funding Information: Supported by the Primary Children’s Hospital Foundation and the National Center for Advancing Translational Sciences of the National Institutes of Health (KL2TR001065).
• Keywords: pediatrics; gamma glutamyltransferase reduction; primary sclerosing cholangitis
• Research Categories: Health Sciences, Nutrition

Abstract

Adverse clinical events in primary sclerosing cholangitis (PSC) happen too slowly to capture during clinical trials. Surrogate endpoints are needed, but no such validated endpoints exist for children with PSC. We evaluated the association between gamma glutamyltransferase (GGT) reduction and long-term outcomes in pediatric PSC patients. We evaluated GGT normalization (< 50 IU/L) at 1 year among a multicenter cohort of children with PSC who did or did not receive treatment with ursodeoxycholic acid (UDCA). We compared rates of event-free survival (no portal hypertensive or biliary complications, cholangiocarcinoma, liver transplantation, or liver-related death) at 5 years. Of the 287 children, mean age of 11.4 years old, UDCA was used in 81% at a mean dose of 17 mg/kg/day. Treated and untreated groups had similar GGT at diagnosis (314 versus 300, P= not significant [NS]). The mean GGT was reduced at 1 year in both groups, with lower values seen in treated (versus untreated) patients (99 versus 175, P= 0.002), but 5-year event-free survival was similar (74% versus 77%, P= NS). In patients with GGT normalization (versus no normalization) by 1 year, regardless of UDCA treatment status, 5-year event-free survival was better (91% versus 67%, P< 0.001). Similarly, larger reduction in GGT over 1 year (> 75% versus < 25% reduction) was also associated with improved outcome (5-year event-free survival 88% versus 61%, P= 0.005). Conclusion:A GGT < 50 and/or GGT reduction of > 75% by 1 year after PSC diagnosis predicts favorable 5-year outcomes in children. GGT has promise as a potential surrogate endpoint in future clinical trials for pediatric PSC.