Acute liver allograft antibody-mediated rejection

An inter-institutional study of significant histopathological features

Jacqueline G. O'Leary, S. Michelle Shiller, Christopher Bellamy, Michael A. Nalesnik, Hugo Kaneku, Linda W. Jennings, Kumiko Isse, Paul I. Terasaki, Göran B. Klintmalm, Anthony J. Demetris

Research output: Contribution to journalArticle

37 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1244-1255
Number of pages12
JournalLiver Transplantation
Volume20
Issue number10
DOIs
StatePublished - Jan 1 2014

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Allografts
Antibodies
Liver
Eosinophilia
Portal Vein
Transplants
Hypertrophy
Endothelial Cells
Staining and Labeling
Inflammation
Isoantibodies
Sensitivity and Specificity
Cholestasis
Hematoxylin
Eosine Yellowish-(YS)
HLA Antigens
Coloring Agents
Odds Ratio
Tissue Donors
Biopsy

ASJC Scopus subject areas

  • Surgery
  • Hepatology
  • Transplantation

Cite this

O'Leary, J. G., Shiller, S. M., Bellamy, C., Nalesnik, M. A., Kaneku, H., Jennings, L. W., ... Demetris, A. J. (2014). Acute liver allograft antibody-mediated rejection: An inter-institutional study of significant histopathological features. Liver Transplantation, 20(10), 1244-1255. https://doi.org/10.1002/lt.23948

Acute liver allograft antibody-mediated rejection : An inter-institutional study of significant histopathological features. / O'Leary, Jacqueline G.; Shiller, S. Michelle; Bellamy, Christopher; Nalesnik, Michael A.; Kaneku, Hugo; Jennings, Linda W.; Isse, Kumiko; Terasaki, Paul I.; Klintmalm, Göran B.; Demetris, Anthony J.

In: Liver Transplantation, Vol. 20, No. 10, 01.01.2014, p. 1244-1255.

Research output: Contribution to journalArticle

O'Leary, JG, Shiller, SM, Bellamy, C, Nalesnik, MA, Kaneku, H, Jennings, LW, Isse, K, Terasaki, PI, Klintmalm, GB & Demetris, AJ 2014, 'Acute liver allograft antibody-mediated rejection: An inter-institutional study of significant histopathological features', Liver Transplantation, vol. 20, no. 10, pp. 1244-1255. https://doi.org/10.1002/lt.23948
O'Leary, Jacqueline G. ; Shiller, S. Michelle ; Bellamy, Christopher ; Nalesnik, Michael A. ; Kaneku, Hugo ; Jennings, Linda W. ; Isse, Kumiko ; Terasaki, Paul I. ; Klintmalm, Göran B. ; Demetris, Anthony J. / Acute liver allograft antibody-mediated rejection : An inter-institutional study of significant histopathological features. In: Liver Transplantation. 2014 ; Vol. 20, No. 10. pp. 1244-1255.
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abstract = "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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