Faculty Collaboration Database

Recurrence of Primary Sclerosing Cholangitis After Liver Transplant in Children: An International Observational Study. Hepatology 2021 Oct;74(4):2047-2057

Date

05/20/2021

Pubmed ID

34008252

Pubmed Central ID

PMC8530456

DOI

10.1002/hep.31911

Scopus ID

2-s2.0-85114458548 (requires institutional sign-in at Scopus site)   7 Citations

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.

Author List

Martinez M, Perito ER, Valentino P, Mack CL, Aumar M, Broderick A, Draijer LG, Fagundes EDT, Furuya KN, Gupta N, Horslen S, Jonas MM, Kamath BM, Kerkar N, Kim KM, Kolho KL, Koot BGP, Laborda TJ, Lee CK, Loomes KM, Miloh T, Mogul D, Mohammed S, Ovchinsky N, Rao G, Ricciuto A, Rodrigues Ferreira A, Schwarz KB, Smolka V, Tanaka A, Tessier MEM, Venkat VL, Vitola BE, Woynarowski M, Zerofsky M, Deneau MR

Authors

Cara Lynn Mack MD Chief, Professor in the Pediatrics department at Medical College of Wisconsin
Bernadette Vitola MD, MPH Associate Professor in the Pediatrics department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Adolescent
Age Factors
Alanine Transaminase
Aspartate Aminotransferases
Child
Cholangitis, Sclerosing
Disease Progression
Drug Resistance
Female
Glucocorticoids
Graft Rejection
Graft Survival
Humans
Hypertension, Portal
Inflammatory Bowel Diseases
Internationality
Liver Transplantation
Male
Recurrence
Registries
Risk Factors
Time Factors
gamma-Glutamyltransferase