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.

Department of Medicine Teikyo University School of Medicine Tokyo Japan

Department of Pediatrics Amsterdam University Medical Center Amsterdam Amsterdam the Netherlands

Department of Pediatrics Amsterdam University Medical Center Amsterdam the Netherlands

Department of Pediatrics Boston Children's Hospital and Harvard Medical School Boston MA

Department of Pediatrics Boston Children's Hospital Boston MA

Department of Pediatrics Children's Health Ireland at Crumlin and University College Dublin Dublin Ireland

Department of Pediatrics Children's Hospital at Montefiore Albert Einstein College of Medicine Bronx NY

Department of Pediatrics Children's Hospital of Philadelphia Philadelphia PA

Department of Pediatrics Children's Hospital of Pittsburgh at UPMC Pittsburgh PA

Department of Pediatrics Columbia University Irving Medical Center New York NY

Department of Pediatrics Emory University School of Medicine Atlanta GA

Department of Pediatrics Faculdade de Medicina da UFMG Belo Horizonte Brazil

Department of Pediatrics Faculty of Medicine and Health Sciences UJK Kielce former IP CZD Warsaw Poland

Department of Pediatrics Federal University of Minas Gerais Belo Horizonte Brazil

Department of Pediatrics Indiana University Indianapolis IN

Department of Pediatrics Johns Hopkins University Baltimore MD

Department of Pediatrics Lurie Children's Hospital Chicago IL

Department of Pediatrics Mayo Clinic Rochester MN

Department of Pediatrics Medical College of Wisconsin Milwaukee WI

Department of Pediatrics Palacky University Olomouc Czech Republic

Department of Pediatrics Texas Children Hospital Houston TX

Department of Pediatrics University of California San Diego San Diego CA

Department of Pediatrics University of California San Francisco San Francisco CA

Department of Pediatrics University of Colorado School of Medicine Aurora CO

Department of Pediatrics University of Miami Miami FL

Department of Pediatrics University of Rochester Medical Center Rochester NY

Department of Pediatrics University of Toronto Toronto ON Canada

Department of Pediatrics University of Ulsan Seoul South Korea

Department of Pediatrics University of Utah and Intermountain Primary Children's Hospital Salt Lake City UT

Department of Pediatrics University of Washington Seattle WA

Department of Pediatrics Yale University School of Medicine New Haven CT

Faculty of Medicine and Health Technology University of Helsinki Hospital and Tampere University Helsinki Finland

Institute for Translational Research in Inflammation University of Lille CHU Lille Lille France

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