patients with higher levels of DSAs, as determined by FC mean fluorescence intensities, had a higher incidence of steroid‐resistant rejection (31% versus 4%).
# Mechanisms for liver allograft AMR‐resistance include 20, 21, 73 the following:
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Kupffer cell DSA clearance of activated complement, platelet aggregates 74, and immune complexes formed between soluble donor HLA class I and anti‐class I DSA 68, 69, 75-77. Supporting evidence includes (i) increased AMR susceptibility and decreased protection of sequentially placed extrahepatic allografts in Kupffer cell–depleted liver allografts 68, 69, 75-77; and (ii) amelioration of acute heart allograft AMR in sensitized recipients by donor class I gene transfection that produces soluble HLA antigens 78.
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Variable hepatic 79 versus constitutive kidney 80 and heart 81 microvascular class II expression providing fewer class II DSA targets, possibly explaining preferential clearance of class I versus class II DSA 82, 83.
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Large liver size dilutes antibody‐binding across a larger endothelial cell surface, potentially explaining increased AMR susceptibility in reduced‐size allografts 77.
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Kupffer and liver sinusoidal endothelial cells Fc receptor expression and phagocytic activity 84-86.
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Hepatic regenerative capacity and ability to heal either without fibrosis or reverse fibrosis 87.
# Probable chronic active AMR (all four criteria are required):
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Histopathological pattern of injury consistent with chronic AMR: both required:
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Recent (for example, measured within 3 months of biopsy) circulating HLA DSA in serum samples;
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At least focal C4d‐positive (>10% portal tract microvascular endothelia) (Figure 5).
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Reasonable exclusion of other insults that might cause a similar pattern of injury (see text).
Possible chronic active AMR:
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As above, but C4d staining is minimal or absent
2016 Comprehensive Update of the Banff Working Group on Liver Allograft Pathology:
