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2014 ; 20
(10
): 1244-55
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Acute liver allograft antibody-mediated rejection: an inter-institutional study
of significant histopathological features
#MMPMID25045154
O'Leary JG
; Michelle Shiller S
; Bellamy C
; Nalesnik MA
; Kaneku H
; Jennings LW
; Isse K
; Terasaki PI
; Klintmalm GB
; Demetris AJ
Liver Transpl
2014[Oct]; 20
(10
): 1244-55
PMID25045154
show ga
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??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.
free
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