TY - JOUR
T1 - Donor-specific alloantibodies are associated with fibrosis progression after liver transplantation in hepatitis C virus-infected patients
AU - O'Leary, Jacqueline G.
AU - Kaneku, Hugo
AU - Jennings, Linda
AU - Susskind, Brian M.
AU - Terasaki, Paul I.
AU - Klintmalm, Göran B.
PY - 2014/6
Y1 - 2014/6
N2 - 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.
AB - 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.
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U2 - 10.1002/lt.23854
DO - 10.1002/lt.23854
M3 - Article
C2 - 24678017
AN - SCOPUS:84897110309
SN - 1527-6465
VL - 20
SP - 655
EP - 663
JO - Liver Transplantation
JF - Liver Transplantation
IS - 6
ER -