The encephalopathy of acetaminophen induced acute liver failure is associated with cerebral endothelial activation

Background

The development of acute hepatic encephalopathy in acute liver failure (ALF) is poorly understood but may be precipitated by sepsis and is associated with sustained elevations of tumor necrosis factor alpha [1]. We have investigated whether the cerebral endothelium of patients with severe encephalopathy has evidence of cytokine induced activation.

Methods

Using immunohistochemistry we have examined the expression of the markers of endothelial activation ICAM-1, VCAM-1 and E-selectin in cerebral vasculature of the brains of 4 acetaminophen induced ALF patients who died of severe encephalopathy and 2 control patients who died sudden cardiac deaths. CD31 was used as a positive control.

Results

CD31 was detected in vessels of all sections studied. No E-selectin expression was detected. Significant ICAM-1 expression and lesser levels of VCAM-1 were detected in the cerebral endothelium ofencephalopathic patients but not in controls.

Conclusions

Acute hepatic encephalopathy is associated with cerebral endothelial activation. The effects of such activation may include changes in blood brain-barrier permeability [2] to the numerous neurologically active substances circulating in ALF and have a direct role in pathogenesis.