What are the salient histopathological features of acute cellular rejection (ACR) of the liver?

From the Guidelines

Acute cellular rejection (ACR) of the liver is primarily diagnosed based on clinical suspicion and histopathological examination, with features including portal inflammation, bile duct damage, and endotheliitis, although the provided evidence does not directly describe these histopathological features 1. The diagnosis of ACR is crucial for the management of liver transplant patients, as it can occur in up to 10% of recipients, most commonly within the first 3 months following transplantation 1.

• Key aspects of ACR diagnosis include:
  • Clinical presentation, which may involve hepatocellular or cholestatic abnormalities in serum liver function tests, and symptoms such as fever, jaundice, and abdominal pain in advanced cases 1.
  • The importance of distinguishing ACR from other conditions like infection, drug toxicity, and recurrent disease through clinical correlation and additional testing.
• While the provided study does not detail the specific histopathological features of ACR, it emphasizes the significance of rejection in the long-term management of liver transplant patients, including its potential progression to chronic rejection and the necessity for appropriate immunosuppressive management 1.
• In clinical practice, the diagnosis and grading of ACR, such as through the Banff schema, are critical for guiding treatment decisions, including adjustments to immunosuppressive regimens or consideration of retransplantation in severe cases 1.

From the Research

Histopathological Features of Acute Cellular Rejection (ACR) of the Liver

The salient histopathological features of ACR of the liver include:

• Portal inflammation, which is a common feature of ACR, but its presence and severity can be affected by pretreatment with immunosuppressive agents 2
• Endothelialitis, which is a characteristic feature of ACR, but can become less prominent with pretreatment 2
• Bile duct damage or inflammation, which can persist even after pretreatment and may be a useful indicator of partially treated ACR 2
• Centrilobular necrosis, central vein endothelialitis, and lobular inflammation, which are common features of ACR and can be predictive of subsequent episodes of ACR or chronic rejection 3, 4
• Portal eosinophilia, which is a significant feature of ACR and can be used to distinguish it from other conditions such as cholangitis 5, 6
• Hepatocellular apoptosis, hepatocellular ballooning, and cholestasis, which can also be seen in ACR, but are not specific to this condition 3, 6

Differential Diagnosis

In the differential diagnosis of ACR, the following features can be useful:

• Ductal changes such as cholestasis, neutrophilic infiltration, proliferation, and periductal fibrosis/edema, which favor cholangitis 5
• The presence and density of portal eosinophilia, which favor ACR 5
• The absence of lymphocytic venulitis and lymphocytic portal inflammation, which can also favor ACR 6

Predictive Value of Histopathological Features

Certain histopathological features can be predictive of subsequent episodes of ACR or chronic rejection, including:

• Pericentral inflammation, centrilobular necrosis, and marked portal eosinophilia, which can indicate a higher risk of subsequent ACR 3
• Centrilobular necrosis, central vein endothelialitis, and lobular inflammation, which can be predictive of chronic rejection 4