Sensitivity and Specificity of Alzheimer Type II Astrocytes in Hepatic Encephalopathy

Abstract

Context.-Hepatic encephalopathy (HE) is associated with presence of type II astrocytes in the brain on the basis of observations made in single uncontrolled cases. This finding was subsequently demonstrated by in vitro studies with replication of microenvironment of HE by increase in ammonia levels. However, no human studies have been done correlating HE with type II astrocytes.Objective.-To determine the sensitivity and specificity of type II astrocytes in HE.Design.-This is a retrospective cohort study in which cases and controls were included. A database search was conducted to identify potential cases of hepatic encephalopathy during a 3-year period, as well as concomitant cases with altered mental status from other causes, liver disease, both, and neither. The presence of HE was determined according to standard clinical criteria, and a coronal section of basal ganglia was selected for examination from each case. Type II astrocytes were enumerated over 20 random high-power fields (HPFs).Results.-Twenty-one patients with HE were identified, with 35 patient controls (18 females, 38 males). Among the patients with HE there was a mean of 19.8 type II astrocytes in 20 HPFs. Patients with altered mental status without HE had an average of 7.2 type II astrocytes per 20 HPFs, and for those without altered mental status, the average was 2.8. For patients with hepatic insufficiency without HE, the average was 11, while for patients with normal hepatic function, the average was 4.1. Overall, for those without HE, the average was 5.4 type II astrocytes per 20 HPFs.Conclusions.-At a cutoff of 5 or more type II astrocytes per 20 HPFs, sensitivity for HE was 85.7% and specificity was 68.6%. Alzheimer type II astrocytes were present in all cases of HE but were also present in a wide variety of patients without HE.H epatic encephalopathy (HE) is a neuropsychiatric disorder that arises in patients with severe hepatic dysfunction and in patients with portosystemic shunts. It manifests as clinical delirium characterized by behavioral changes and cognitive impairment. 1 In severity, manifestations vary from irritability to delirium, stupor, and coma. In a study by Fichet et al, 2 hepatic encephalopathy was associated with a mortality of 54% at 1 year.A distinct cell type was first noted by von Hösslin and Alzheimer in 1912 and came to be known as the Alzheimer type II astrocyte, the histopathologic hallmark of HE. 3,4 Hyperammonemia results when, because blood bypasses the liver or passes through dysfunctional liver, ammonia is insufficiently converted to urea. [5][6][7][8] This is thought to be the cause of neurologic dysfunction in HE. Furthermore, experimental evidence demonstrates that the distinctive morphologic features of type II astrocytes can be induced by ammonia in vitro, and observational studies confirm that type II astrocytes are observed in animals and human patients with HE. 9-11 It is thought that these changes reflect induction of neuroprotective metabolic pathways in astrocytes in the hyperammonemic environment...

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