From the Guidelines
Antibody-mediated rejection (AMR) in liver transplantation is characterized by several key histopathological features, including portal vein and sinusoidal endothelial cell swelling, C4d deposition along portal veins and sinusoids, portal microvascular disruption, and portal microvasculitis with neutrophilic infiltration, as well as ductular reaction, cholestasis, hepatocyte ballooning, and sometimes fibrinoid necrosis of portal vessels. These features are crucial for the diagnosis of AMR, which is less common in liver transplants compared to other solid organs due to the liver's inherent resistance to antibody-mediated injury 1. The presence of donor-specific antibodies (DSAs) correlates with these findings, particularly when they target class II HLA antigens, and diagnosis typically requires correlation of histopathological findings with serological evidence of DSAs and clinical presentation 1. Some of the key histopathological features of AMR in liver transplantation include:
- Portal vein and sinusoidal endothelial cell swelling
- C4d deposition along portal veins and sinusoids
- Portal microvascular disruption
- Portal microvasculitis with neutrophilic infiltration
- Ductular reaction
- Cholestasis
- Hepatocyte ballooning
- Fibrinoid necrosis of portal vessels
- Monocyte and macrophage infiltration in portal tracts and sinusoids It is essential to note that C4d staining in liver AMR can be patchy and less reliable as a standalone marker, unlike in kidney or heart transplants 1. Therefore, a comprehensive approach to diagnosis, including correlation of histopathological findings with serological evidence of DSAs and clinical presentation, is necessary for proper management of AMR in liver transplantation.
From the Research
Histopathological Features of Antibody-Mediated Rejection (AMR) in the Liver
The salient histopathological features of AMR in the liver include:
- Portal eosinophilia
- Portal vein endothelial cell hypertrophy
- Eosinophilic central venulitis
- Central venulitis severity
- Cholestasis 2
- Microvascular injury/microvasculitis consistent with antibody-mediated injury 3, 4
- Diffuse C4d staining in the portal microvasculature with or without staining in the sinusoids or central veins 3, 4
- CD163 immunohistochemistry 5
- Banff H-score 5
- Moderate to severe cholestasis 5
- Bile ductular reaction 5
- Central perivenulitis 5
Diagnostic Approaches
The diagnosis of AMR in the liver allograft requires a combination of clinical work-up, histopathology, C4d staining, and donor-specific antibody (DSA) testing 6, 4. The use of strict criteria for defining "pure" AMR is essential, including graft dysfunction associated with compatible histological findings, the presence of DSAs, and diffusely positive staining for C4d 4.
Predictors of Serum DSA Positivity
Significant histopathological predictors of serum DSA positivity include: