TY - JOUR
T1 - Acute liver allograft antibody-mediated rejection
T2 - An inter-institutional study of significant histopathological features
AU - O'Leary, Jacqueline G.
AU - Shiller, S. Michelle
AU - Bellamy, Christopher
AU - Nalesnik, Michael A.
AU - Kaneku, Hugo
AU - Jennings, Linda W.
AU - Isse, Kumiko
AU - Terasaki, Paul I.
AU - Klintmalm, Göran B.
AU - Demetris, Anthony J.
N1 - Publisher Copyright:
© 2014 AASLD.
PY - 2014/10/1
Y1 - 2014/10/1
N2 - Acute antibody-mediated rejection (AMR) occurs in a small minority of sensitized liver transplant recipients. Although histopathological characteristics have been described, specific features that could be used (1) to make a generalizable scoring system and (2) to trigger a more in-depth analysis are needed to screen for this rare but important finding. Toward this goal, we created training and validation cohorts of putative acute AMR and control cases from 3 high-volume liver transplant programs; these cases were evaluated blindly by 4 independent transplant pathologists. Evaluations of hematoxylin and eosin (H&E) sections were performed alone without knowledge of either serum donor-specific human leukocyte antigen alloantibody (DSA) results or complement component 4d (C4d) stains. Routine histopathological features that strongly correlated with severe acute AMR included portal eosinophilia, portal vein endothelial cell hypertrophy, eosinophilic central venulitis, central venulitis severity, and cholestasis. Acute AMR inversely correlated with lymphocytic venulitis and lymphocytic portal inflammation. These and other characteristics were incorporated into models created from the training cohort alone. The final acute antibody-mediated rejection score (aAMR score)-the sum of portal vein endothelial cell hypertrophy, portal eosinophilia, and eosinophilic venulitis divided by the sum of lymphocytic portal inflammation and lymphocytic venulitis-exhibited a strong correlation with severe acute AMR in the training cohort [odds ratio (OR)=2.86, P<0.001] and the validation cohort (OR=2.49, P<0.001). SPSS tree classification was used to select 2 cutoffs: one that optimized specificity at a score>1.75 (sensitivity=34%, specificity=86%) and another that optimized sensitivity at a score>1.0 (sensitivity=81%, specificity=71%). In conclusion, the routine histopathological features of the aAMR score can be used to screen patients for acute AMR via routine H&E staining of indication liver transplant biopsy samples; however, a definitive diagnosis requires substantiation by DSA testing, diffuse C4d staining, and the exclusion of other insults. Liver Transpl 20:1244-1255, 2014.
AB - Acute antibody-mediated rejection (AMR) occurs in a small minority of sensitized liver transplant recipients. Although histopathological characteristics have been described, specific features that could be used (1) to make a generalizable scoring system and (2) to trigger a more in-depth analysis are needed to screen for this rare but important finding. Toward this goal, we created training and validation cohorts of putative acute AMR and control cases from 3 high-volume liver transplant programs; these cases were evaluated blindly by 4 independent transplant pathologists. Evaluations of hematoxylin and eosin (H&E) sections were performed alone without knowledge of either serum donor-specific human leukocyte antigen alloantibody (DSA) results or complement component 4d (C4d) stains. Routine histopathological features that strongly correlated with severe acute AMR included portal eosinophilia, portal vein endothelial cell hypertrophy, eosinophilic central venulitis, central venulitis severity, and cholestasis. Acute AMR inversely correlated with lymphocytic venulitis and lymphocytic portal inflammation. These and other characteristics were incorporated into models created from the training cohort alone. The final acute antibody-mediated rejection score (aAMR score)-the sum of portal vein endothelial cell hypertrophy, portal eosinophilia, and eosinophilic venulitis divided by the sum of lymphocytic portal inflammation and lymphocytic venulitis-exhibited a strong correlation with severe acute AMR in the training cohort [odds ratio (OR)=2.86, P<0.001] and the validation cohort (OR=2.49, P<0.001). SPSS tree classification was used to select 2 cutoffs: one that optimized specificity at a score>1.75 (sensitivity=34%, specificity=86%) and another that optimized sensitivity at a score>1.0 (sensitivity=81%, specificity=71%). In conclusion, the routine histopathological features of the aAMR score can be used to screen patients for acute AMR via routine H&E staining of indication liver transplant biopsy samples; however, a definitive diagnosis requires substantiation by DSA testing, diffuse C4d staining, and the exclusion of other insults. Liver Transpl 20:1244-1255, 2014.
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U2 - 10.1002/lt.23948
DO - 10.1002/lt.23948
M3 - Article
C2 - 25045154
AN - SCOPUS:84908545973
SN - 1527-6465
VL - 20
SP - 1244
EP - 1255
JO - Liver Transplantation
JF - Liver Transplantation
IS - 10
ER -