title: Donor-specific alloantibodies are associated with fibrosis progression after liver transplantation in hepatitis C virus-infected patients.
abstract: Hepatitis C virus (HCV) fibrosis progression after liver transplantation (LT) is accelerated in comparison with fibrosis progression before transplantation. The vast majority of the risk factors for fibrosis progression after LT are not modifiable. With the goal of identifying modifiable risk factors for fibrosis progression, we evaluated the impact of preformed and de novo donor-specific human leukocyte antigen alloantibodies (DSAs) on fibrosis progression after LT in HCV-viremic patients. After blinding, we analyzed all 507 HCV-viremic patients who underwent primary LT from January 2000 to May 2009 and had pretransplant and posttransplant samples available for analysis (86% of the total) for preformed and de novo class I and class II DSAs with a mean fluorescence intensity ≥ 5000 with single-antigen bead technology. Fibrosis was assessed on the basis of indication and protocol liver biopsies; compliance with protocol liver biopsies at 1, 2, and 5 years was ≥80%. Preformed class I DSAs [hazard ratio (HR) = 1.44, P = 0.04] and class II DSAs (HR = 1.86, P < 0.001) were independent predictors of progression to stage 2-4 fibrosis, and de novo DSAs (HR = 1.41, P = 0.07) had borderline significance. In addition, preformed class I DSAs (HR = 1.63, P = 0.03) and class II DSAs (HR = 1.72, P = 0.03) were statistically significantly associated with an increased risk of death. In conclusion, after we controlled for donor and recipient characteristics in multivariate modeling, DSAs were independently associated with fibrosis progression and death after LT in HCV-viremic patients.
authors.affiliation: Annette C. and Harold C. Simmons Transplant Institute, Baylor University Medical Center, Dallas, TX.
authors.forename: Jacqueline G
authors.initials: JG
authors.lastname: O'Leary
authors.forename: Hugo
authors.initials: H
authors.lastname: Kaneku
authors.forename: Linda
authors.initials: L
authors.lastname: Jennings
authors.forename: Brian M
authors.initials: BM
authors.lastname: Susskind
authors.forename: Paul I
authors.initials: PI
authors.lastname: Terasaki
authors.forename: Göran B
authors.initials: GB
authors.lastname: Klintmalm
mesh_terms: D015415:Biomarkers / Q000097:blood; D001706:Biopsy; D018450:Disease Progression; D005260:Female; D006680:HLA Antigens / Q000276:immunology*; D006526:Hepatitis C / Q000150:complications / Q000175:diagnosis / Q000276:immunology* / Q000401:mortality; D006801:Humans; D007518:Isoantibodies / Q000097:blood*; D053208:Kaplan-Meier Estimate; D008103:Liver Cirrhosis / Q000175:diagnosis / Q000276:immunology* / Q000401:mortality / Q000601:surgery* / Q000821:virology; D016031:Liver Transplantation / Q000009:adverse effects* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D011237:Predictive Value of Tests; D012189:Retrospective Studies; D012307:Risk Factors; D016896:Treatment Outcome
chemical_list: D015415:Biomarkers; D006680:HLA Antigens; D007518:Isoantibodies