title: Risk factors for recurrence of primary sclerosing cholangitis after liver transplantation.
abstract: Orthotopic liver transplantation (OLT) is the only effective treatment for end-stage liver disease due to primary sclerosing cholangitis (PSC). Recurrence of PSC has recently emerged as a leading cause of allograft failure in the long term. There is limited data on risk factors for recurrence of PSC. We performed a retrospective analysis of 69 consecutive patients who underwent a first OLT for PSC over a 14-year period. Baseline characteristics and clinical and laboratory test results post-LT were recorded. Cholangiograms and liver histopathology were reviewed in a blinded manner by an experienced radiologist and hepatopathologist. Recurrent PSC was diagnosed using previously published Mayo Clinic cholangiographic or histologic criteria. Of 69 patients, 7 (10%) developed recurrent PSC at a median of 68 months (range, 24-134 months) post-LT. The following variables were associated with recurrent PSC in our cohort: presence of human leukocyte antigen (HLA)-DRB1*08 (29% versus 2%; P= 0.026; odds ratio [OR], 24.4; 95% confidence interval [CI], 1.8-318.1), acute cellular rejection (ACR) (71% versus 22%; P= 0.015; OR, 8.7; 95% CI, 1.5-49.9), and steroid-resistant ACR (29% versus 0%; P= 0.012). Despite the strong linkage disequilibrium between DRB1*08 and DQB1*04, DRB1*08-positive subjects with recurrence were negative for DQB1*04, whereas the single DRB1*08-positive subject without recurrent PSC was positive for DQB1*04. A history of ACR and presence of HLA-DRB1*08 are associated with increased risk of recurrent PSC, suggesting an immunologic mechanism for this syndrome. Further studies are required to confirm these observations and to understand the underlying mechanisms.
authors.affiliation: Division of Gastroenterology, Department of Medicine, University of Washington, Seattle, WA, USA.
authors.forename: Jacob
authors.initials: J
authors.lastname: Alexander
authors.forename: James D
authors.initials: JD
authors.lastname: Lord
authors.forename: Matthew M
authors.initials: MM
authors.lastname: Yeh
authors.forename: Carlos
authors.initials: C
authors.lastname: Cuevas
authors.forename: Ramasamy
authors.initials: R
authors.lastname: Bakthavatsalam
authors.forename: Kris V
authors.initials: KV
authors.lastname: Kowdley
mesh_terms: D000328:Adult; D000368:Aged; D002758:Cholangiography; D015209:Cholangitis, Sclerosing / Q000000981:diagnostic imaging / Q000235:genetics / Q000276:immunology / Q000401:mortality / Q000601:surgery*; D018572:Disease-Free Survival; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006084:Graft Rejection / Q000150:complications; D006684:HLA-DR Antigens / Q000235:genetics; D059811:HLA-DRB1 Chains; D006801:Humans; D053208:Kaplan-Meier Estimate; D016031:Liver Transplantation; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D012008:Recurrence; D012086:Reoperation; D012189:Retrospective Studies; D018570:Risk Assessment; D012307:Risk Factors; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D006684:HLA-DR Antigens; D059811:HLA-DRB1 Chains