Is It Covert or Overt Hepatic Encephalopathy?

Rowen K. Zetterman, MD


November 21, 2016


The establishment of a clinical diagnosis of minimal or covert encephalopathy is difficult because there are no specific agreed-upon tests to identify its presence, and because it requires a heightened sense of suspicion in a patient with cirrhosis in the absence of disorientation or asterixis. Some of the above-mentioned clinical findings, such as alterations in sleep, a history of auto accidents or driving violations, and other abnormalities noted by the patient's spouse, can be an indication of the diagnosis. For patients with suspected encephalopathy, other central nervous system (CNS) disorders, including CNS hemorrhage, should be excluded.[1,18,19]

A diagnosis of covert encephalopathy can prompt the patient and family to prepare for the eventual risks related to overt encephalopathy, the potential treatments needed, and the social difficulties involved, such as driving restrictions.

To establish the presence of minimal or covert hepatic encephalopathy, a number of tests have been suggested:

  • Blood ammonia levels. Although ammonia can play a role in the pathogenesis of hepatic encephalopathy, levels of venous or arterial ammonia do not always correlate with the severity of encephalopathy,[20] and fail to add any specificity to the diagnosis of patients with covert or overt encephalopathy.

  • Number-connection tests. Number-connection, block-design, and picture-completion tests can help make a diagnosis in a person with suspected hepatic encephalopathy[9] and are part of the psychometric hepatic encephalopathy score.

  • Inhibitory-control test. This test evaluates attention and response inhibition[21] after a brief presentation of a sequence of letters, and relates to the severity of cirrhosis and encephalopathy. Testing abnormality is greater in those with MELD scores above 12 or an elevated Child–Pugh score. The test requires a highly functioning patient.[1]

  • Electroencephalogram (EEG). An EEG can detect slow-wave frequency in patients with hepatic encephalopathy. Slow-wave changes also occur in other metabolic encephalopathies, so sensitivity is variable.[20]

  • Psychometric hepatic encephalopathy score (PHES). The PHES uses an aggregate score of five tests: number-connection test A, number-connection test B, a digital symbol test, a line-tracing test, and a serial-dotting test.[20,21] These tests evaluate the psychomotor function of the patient and identify subtle cognitive impairment by assessing dexterity, reaction time, and steadiness.

  • Critical flicker-frequency analysis. The critical flicker-frequency analysis uses a flickering light with a progressively decreasing frequency as a measure of cortical function.[22] Patients are asked to note when they first recognize that the light is flickering. Correlation between the characteristics of encephalopathy and the PHES is noted.[22] The advantage of this test is the ease of administration, but patients are required to have intact binocular vision. This test has also been used to identify patients at risk for post-TIPS overt encephalopathy.[12] Those lacking minimal hepatic encephalopathy on the critical flicker testing are less likely to develop overt encephalopathy after TIPS.

  • Smartphone testing. The Stroop test evaluates the interference in reaction time and psychomotor speed that develops with covert hepatic encephalopathy. A smartphone application (EncephalApp Stroop Test) has been used as a screening tool for covert encephalopathy[23] and is recognized as an acceptable testing method.[24]


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