Transplant Pathology Internet Services

Acute/Active Antibody-Mediated Liver Allograft Rejection and Scoring of Components

Diagnosis of Acute/Active AMR

Criteria for Diagnosis

1. Histopathology

2. DSA (Donor-specific antibody)

3. C4d Immunostain

4. Other

5. Overall Scores

Definite for AMR

(criteria 1-4 required, criterion 5 derives from these)

(See below for component scoring: overall h-score =2-3) Usually present:
a. Portal microvascular endothelial cell hypertrophy
b. Dilatation of portal capillaries and inlet venules
c. Portal microvasculitis (monocytic, eosinophilic and/or neutrophilic)
d. Portal edema
e. Ductular reaction

Other features:
f. Cholestasis (usually present but variable)
g. Edema with periportal necrosis (more common/prominent with ABO mismatch)
h. Lymphocytic and/or necrotizing arteritis (variable)

Positive serum DSA

(See below for component scoring)
Diffuse microvascular C4d deposition (score=3) on frozen or formalin fixed-paraffin-embedded tissue in ABO-compatible graft

OR
Portal stromal C4d deposition in ABO-incompatible graft

(Assumes optimized C4d staining with adequate positive control)

Reasonably exclude other insults causing similar injury pattern

Most cases will have C4d score of 3 and h-score of 2-3 for total of 5-6.

Suspicious for AMR
(criteria 1, 2 and 5 required)

h-score >0

Positive serum DSA

C4d score + h-score = 3-4

Indeterminate for AMR
(criteria 2, 3 and 5 OR 2, 4 and 5 required)

DSA negative, equivocal or not available

C4d stain negative (score=0), equivocal or not available

Coexisting insult might be contributing to injury

C4d score + h-score =2 or greater

h score (Histopathology Score) for Acute/Active AMR Components

Score

Components

Portal Microvascular Endothelial Cells

Microvasculitis

Microvascular Dilatation

Portal Edema

Microvascular Injury

Portal microvascular endothelial cell enlargement (portal veins, capillaries, inlet venules) involving majority of portal tracts

Sparse microvasculitis (3-4 marginated and/or intraluminal monocytes, neutrophils or eosinophils in maximally involved capillary

Generally mild

Prominent portal and/or sinusoidal microvascular endothelial cell enlargement involving majority of portal tracts or sinusoids

Microvasculitis/capillaritis (at least 5-10 marginated and/or intraluminal monocytes, neutrophils or eosinophils in the maximally involved capillary)

Variable but noticeable portal capillary and inlet venule dilatation

Variable

Prominent portal and/or sinusoidal microvascular endothelial cell enlargement involving majority of portal tracts or sinusoids

Marked microvasculitis/capillaritis (10 or more marginated and/or intraluminal monocytes, neutrophils or capillaries in the maximally involved capillary)

Marked capillary dilatation

Variable

At least focal microvascular disription with fibrin deposition and extravasation of red blood cells into portal stroma and/or Space of Disse

C4d (Immune) Score for Acute/Active AMR Components

Score

Appearance in Formalin-fixed, Paraffin-embedded Tissue

No C4d deposition in portal microvasculature

Minimal (<10% of portal tracts) C4d deposition in >50% of the circumference of portal microvascular endothelia (portal veins and capillaries)

Focal (10-50% of portal tracts) C4d deposition in >50% of the circumference of portal microvascular endothelia (portal veins and capillaries), usually without extension into periportal sinusoids

Diffuse (>50% of portal tracts) C4d deposition in >50% of the circumference of portal microvascular endothelia (portal vaines and capillaries), often with extension into inlet venules or periportal sinusoids