A 34-year-old man is evaluated due to elevated liver aminotransferases. The patient has no chronic medical conditions but has a history of injection drug use. Family history is notable for liver cirrhosis in his mother. Ultrasonography-guided liver biopsy is performed. Histopathology demonstrates marked panlobular mononuclear cell infiltration that spans adjacent lobules. Intensely eosinophilic round bodies are occasionally seen scattered among the hepatic parenchyma. Which of the following is the most likely cause of the latter histopathologic finding in this patient?
This patient with a history of intravenous drug use likely has elevated aminotransferases due to acute viral hepatitis, which is characterized by hepatocyte damage (eg, cell injury, cell death) and inflammation.
Most cases are marked by significant panlobular lymphocytic inflammation (ie, involving the entire lobule), which develops in response to the viral antigens. To control the infection, cytotoxic T cells trigger apoptosis of infected hepatocytes by binding death receptors (eg, Fas) on the plasma membrane and by secreting cytotoxic mediators (eg, perforins, granzymes). As a result, a cascade of caspase enzymes breaks down hepatocyte proteins and DNA, leading to cell shrinkage, chromatin condensation and fragmentation, and budding apoptotic bodies (ie, membrane-bound cellular fragments).
In liver biopsy, these apoptotic hepatocytes (ie, Councilman bodies, acidophil bodies) have a small, round, intensely pink (ie, eosinophilic) appearance on hematoxylin and eosin staining and may contain pyknotic nuclei or nuclear fragments. They are typically promptly phagocytosed by Kupffer cells.
(Choice A) Toxin-mediated hepatic injury (eg, due to acetaminophen) often results in centrilobular hepatocyte necrosis (ie, centered around central veins) due to oxidative damage.
(Choice C) Hemochromatosis is characterized by the deposition of iron within hepatocytes, which appears as yellow to brown granules that can be highlighted with Prussian blue stain.
(Choice D) Mallory bodies, damaged cytokeratin filaments that appear as eosinophilic hepatocellular inclusions, often arise in alcoholic liver disease. Alcohol-mediated liver injury is associated with fat deposition in hepatocytes, particularly in the centrilobular region.
(Choice E) Aschoff bodies, seen in the myocardium of patients with rheumatic heart disease, are small areas of granulomatous inflammation that may contain central fibrinoid necrosis. They are not seen in the liver.
(Choice F) Stellate cells, which reside in the hepatic perisinusoidal space, can transdifferentiate into myofibroblasts in response to hepatocyte injury and deposit collagen, resulting in liver fibrosis. Fibrotic bands may develop in chronic viral hepatitis, which is characterized by persistent hepatocyte injury and predominantly portal tract–based lymphocytic inflammation.
Educational objective:
Intravenous drug use is a risk factor for acute viral hepatitis, which is marked by panlobular inflammation, hepatocyte injury, and cell death. To control the infection, cytotoxic T-cell–mediated signals cause hepatocyte apoptosis, which is characterized microscopically by Councilman bodies (ie, round, intensely eosinophilic bodies).