Mercedes Martinez1, Emily R Perito2, Pamela Valentino3, Cara L Mack4, Madeleine Aumar5, Annemarie Broderick6, Laura G Draijer7, Eleonora D T Fagundes8, Katryn N Furuya9,10, Nitika Gupta11, Simon Horslen12, Maureen M Jonas13, Binita M Kamath14, Nanda Kerkar15, Kyung Mo Kim16, Kaija-Leena Kolho17, Bart G P Koot18, Trevor J Laborda19, Christine K Lee20, Kathleen M Loomes21, Tamir Miloh22, Douglas Mogul23, Saeed Mohammed24, Nadia Ovchinsky25, Girish Rao26, Amanda Ricciuto14, Alexandre Rodrigues Ferreira27, Kathleen B Schwarz28,23, Vratislav Smolka29, Atsushi Tanaka30, Mary E M Tessier31, Venna L Venkat32, Bernadette E Vitola10, Marek Woynarowski33, Melissa Zerofsky34, Mark R Deneau19. 1. Department of Pediatrics, Columbia University Irving Medical Center, New York, NY. 2. Department of Pediatrics, University of California, San Francisco, San Francisco, CA. 3. Department of Pediatrics, Yale University School of Medicine, New Haven, CT. 4. Department of Pediatrics, University of Colorado School of Medicine, Aurora, CO. 5. Institute for Translational Research in Inflammation, University of Lille, CHU Lille, Lille, France. 6. Department of Pediatrics, Children's Health Ireland at Crumlin & University College Dublin, Dublin, Ireland. 7. Department of Pediatrics, Amsterdam University Medical Center, Amsterdam, the Netherlands. 8. Department of Pediatrics, Federal University of Minas Gerais, Belo Horizonte, Brazil. 9. Department of Pediatrics, Mayo Clinic, Rochester, MN. 10. Department of Pediatrics, Medical College of Wisconsin, Milwaukee, WI. 11. Department of Pediatrics, Emory University School of Medicine, Atlanta, GA. 12. Department of Pediatrics, University of Washington, Seattle, WA. 13. Department of Pediatrics, Boston Children's Hospital and Harvard Medical School, Boston, MA. 14. Department of Pediatrics, University of Toronto, Toronto, ON, Canada. 15. Department of Pediatrics, University of Rochester Medical Center, Rochester, NY. 16. Department of Pediatrics, University of Ulsan, Seoul, South Korea. 17. Faculty of Medicine and Health Technology, University of Helsinki Hospital and Tampere University, Helsinki, Finland. 18. Department of Pediatrics, Amsterdam University Medical Center Amsterdam, Amsterdam, the Netherlands. 19. Department of Pediatrics, University of Utah and Intermountain Primary Children's Hospital, Salt Lake City, UT. 20. Department of Pediatrics, Boston Children's Hospital, Boston, MA. 21. Department of Pediatrics, Children's Hospital of Philadelphia, Philadelphia, PA. 22. Department of Pediatrics, University of Miami, Miami, FL. 23. Department of Pediatrics, Johns Hopkins University, Baltimore, MD. 24. Department of Pediatrics, Lurie Children's Hospital, Chicago, IL. 25. Department of Pediatrics, Children's Hospital at Montefiore, Albert Einstein College of Medicine, Bronx, NY. 26. Department of Pediatrics, Indiana University, Indianapolis, IN. 27. Department of Pediatrics, Faculdade de Medicina da UFMG, Belo Horizonte, Brazil. 28. Department of Pediatrics, University of California San Diego, San Diego, CA. 29. Department of Pediatrics, Palacky University, Olomouc, Czech Republic. 30. Department of Medicine, Teikyo University School of Medicine, Tokyo, Japan. 31. Department of Pediatrics, Texas Children Hospital, Houston, TX. 32. Department of Pediatrics, Children's Hospital of Pittsburgh at UPMC, Pittsburgh, PA. 33. Department of Pediatrics, Faculty of Medicine and Health Sciences, UJK Kielce, former IP CZD Warsaw, Poland. 34. Department of Pediatrics, University of California San Francisco, San Francisco, CA.
Abstract
BACKGROUND AND AIMS: Recurrent primary sclerosing cholangitis (rPSC) following liver transplant (LT) has a negative impact on graft and patient survival; little is known about risk factors for rPSC or disease course in children. APPROACH AND RESULTS: We retrospectively evaluated risk factors for rPSC in 140 children from the Pediatric PSC Consortium, a multicenter international registry. Recipients underwent LT for PSC and had >90 days of follow-up. The primary outcome, rPSC, was defined using Graziadei criteria. Median follow-up after LT was 3 years (interquartile range 1.1-6.1). rPSC occurred in 36 children, representing 10% and 27% of the subjects at 2 years and 5 years following LT, respectively. Subjects with rPSC were younger at LT (12.9 vs. 16.2 years), had faster progression from PSC diagnosis to LT (2.5 vs. 4.1 years), and had higher alanine aminotransferase (112 vs. 66 IU/L) at LT (all P < 0.01). Inflammatory bowel disease was more prevalent in the rPSC group (86% vs. 66%; P = 0.025). After LT, rPSC subjects had more episodes of biopsy-proved acute rejection (mean 3 vs. 1; P < 0.001), and higher prevalence of steroid-refractory rejection (41% vs. 20%; P = 0.04). In those with rPSC, 43% developed complications of portal hypertension, were relisted for LT, or died within 2 years of the diagnosis. Mortality was higher in the rPSC group (11.1% vs. 2.9%; P = 0.05). CONCLUSIONS: The incidence of rPSC in this cohort was higher than previously reported, and was associated with increased morbidity and mortality. Patients with rPSC appeared to have a more aggressive, immune-reactive phenotype. These findings underscore the need to understand the immune mechanisms of rPSC, to lay the foundation for developing new therapies and improve outcomes in this challenging population.
BACKGROUND AND AIMS: Recurrent primary sclerosing cholangitis (rPSC) following liver transplant (LT) has a negative impact on graft and patient survival; little is known about risk factors for rPSC or disease course in children. APPROACH AND RESULTS: We retrospectively evaluated risk factors for rPSC in 140 children from the Pediatric PSC Consortium, a multicenter international registry. Recipients underwent LT for PSC and had >90 days of follow-up. The primary outcome, rPSC, was defined using Graziadei criteria. Median follow-up after LT was 3 years (interquartile range 1.1-6.1). rPSC occurred in 36 children, representing 10% and 27% of the subjects at 2 years and 5 years following LT, respectively. Subjects with rPSC were younger at LT (12.9 vs. 16.2 years), had faster progression from PSC diagnosis to LT (2.5 vs. 4.1 years), and had higher alanine aminotransferase (112 vs. 66 IU/L) at LT (all P < 0.01). Inflammatory bowel disease was more prevalent in the rPSC group (86% vs. 66%; P = 0.025). After LT, rPSC subjects had more episodes of biopsy-proved acute rejection (mean 3 vs. 1; P < 0.001), and higher prevalence of steroid-refractory rejection (41% vs. 20%; P = 0.04). In those with rPSC, 43% developed complications of portal hypertension, were relisted for LT, or died within 2 years of the diagnosis. Mortality was higher in the rPSC group (11.1% vs. 2.9%; P = 0.05). CONCLUSIONS: The incidence of rPSC in this cohort was higher than previously reported, and was associated with increased morbidity and mortality. Patients with rPSC appeared to have a more aggressive, immune-reactive phenotype. These findings underscore the need to understand the immune mechanisms of rPSC, to lay the foundation for developing new therapies and improve outcomes in this challenging population.
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