Minimal Hepatic Encephalopathy -- An Occult, Prevalent, and Important Problem

David A. Johnson, MD, FACG, FASGE, FACP


January 06, 2009

Patients With Minimal Hepatic Encephalopathy Have Poor Insight Into Their Driving Skills

Bajaj JS, Saeian K, Hafeezullah M, Hoffmann RG Hammeke TA
Clin Gastroenterol Hepatol. 2008;6:1135-1139



Inhibitory Control Test for the Diagnosis of Minimal Hepatic Encephalopathy


Bajaj JS, Hafeezullah M, Franco J, et al
Gastroenterology. 2008;135:1591-1600



Computerized Psychometric Testing in Minimal Encephalopathy and Modulation by Nitrogen Challenge and Liver Transplant


Mardini H, Saxby BK, Record CO
Gastroenterology. 2008;135:1582-1590


Editor's Note

Dr. Johnson's summary and commentary collaboratively address these 3 reports on the clinically important entity of minimal hepatic encephalopathy and the importance of recognizing this extremely prevalent condition.


Minimal hepatic encephalopathy is a significant complication of cirrhosis that results in neurocognitive impairment. This leads to a poor quality of life and is associated with a progression to the more overt hepatic encephalopathy. When appropriate testing is done, this condition is evident in up to 80% of patients with cirrhosis. Unfortunately, this diagnosis is rarely made, as a battery of complex psychomotor testing is required to establish the diagnosis. Several factors further hinder the diagnosis, including a need for psychological expertise for the clinical administration and interpretation of these tests, which are also costly and copyrighted, as well as the lack of reimbursement by insurance companies. Therefore, the result is a prevalent condition that is not identified by a confirmed diagnosis. The importance of minimal hepatic encephalopathy has taken on new weight, however, with reports of impairment in driving.

It has been recently reported that patients with minimal hepatic encephalopathy have an increased occurrence of traffic violations and vehicle-related accidents.[1] This makes sense given that minimal hepatic encephalopathy results in a spectrum of cognitive impairments -- in particular, for domains of attention, vigilance, response inhibition, and executive function. Furthermore it has been suggested that insight or self-awareness of driving impairment is poorly appreciated in patients with minimal hepatic encephalopathy. Because patients with minimal hepatic encephalopathy have no specific symptoms, it would be extremely important then to establish the diagnosis and hopefully, to counsel and treat these patients whereby the adverse driving outcomes might be avoided.

To study this further, Bajaj and colleagues evaluated 47 nonalchoholic cirrhotic patients and 40 control patients who underwent a battery of psychomometric tests and a driving simulation to assess response and navigation capabilities. Additionally, a validated Driving Behavior Survey questionnaire was given to both the subjects as well as an adult familiar with the subject's driving performance. Patients who had consumed alcohol within the prior 6 months or who were being treated for overt encephalopathy were excluded from the trial. The driving simulator involved a navigation task of driving on a fixed path while consulting a map on the simulator. Illegal turns were recorded and collisions were the primary outcome assessment.

Thirty-six patients met the criteria for minimal hepatic encephalopathy. These patients demonstrated significantly worse performance in driving skill scores compared with patients with cirrhosis without minimal hepatic encephalopathy and healthy controls. These patients demonstrated increased rates of illegal turns (P = .0001) and crashes (P = .001). Despite this poorer performance, there was no difference in the self-assessed driving skills by the patients with or without minimal hepatic encephalopathy or controls. However, when assessed by the adult familiar with the driving performance of those subjects, the patients with minimal hepatic encephalopathy were rated significantly lower for driving skills (P = .02).

The other 2 studies focused on new and more standardized testing for minimal hepatic encephalopathy. The second report by Bajaj and colleagues assessed the utility of the Inhibitory Control Test (ICT), which is a computerized test of attention and response inhibition. This test was previously used in patients with attention-deficit disorder, schizophrenia, and traumatic brain injury. The results of this study served to validate this test for use in the diagnosis of minimal hepatic encephalopathy. The study authors demonstrated that the ICT is a sensitive, reliable, and valid test to establish the diagnosis. Furthermore, the ICT can be administered inexpensively by medical assistants. Of particular note is that the authors committed to making a modified version of the ICT freely available to the public. Additionally, because the ICT involves recognition of specific letters, it can be potentially administered to non-English speaking subjects with minimal modification.

Finally, the report by Mardini and colleagues compared standard paper-and-pencil neuropsychologic testing with a comprehensive computerized assessment of cognitive function for the diagnosis of minimal hepatic encephalopathy. They found a significantly high correlation between the 2 methods of assessment (P = .001). Furthermore, the computerized testing suggesting impaired function was significantly correlated (P = .001) with a higher venous ammonia level, which historically has been the laboratory correlate for hepatic encephalopathy. The study authors also demonstrated a return to the control range for cognitive function in a subset cohort of patients who were followed after liver transplantation.


Although a working party on hepatic encephalopathy provided guidelines for the diagnosis of minimal hepatic encephalopathy,[2] this diagnosis is rarely established by hepatologists and much less so by general gastroenterologists who provide care for patients with cirrhosis. The importance of recognizing this extremely prevalent condition has now taken on new meaning with the association of poor driving performance, including illegal turns and crashes. The importance of this association, however, is heightened by the lack of insight by patients with minimal hepatic encephalopathy as to their driving impairment. Given that insight into a disease state is one of the most significant forces that can lead to the patient seeing healthcare, this lack of insight means that the impairment will likely go unrecognized and thereby not appropriately treated. Because of this, clinicians who treat patients with cirrhosis without overt encephalopathy should begin to discuss driving performance history with those patients as well as with relatives or caregivers familiar with their driving practice.

The implications of there being more available and computerized testing for minimal hepatic encephalopathy are that these tests will hopefully soon become more standard for testing in physicians' offices or clinics and that this condition will thus become more widely recognized. Although the driving impairments associated with minimal hepatic encephalopathy are evident, it is likely but yet not proven, that these impairments will be responsive to treatment strategies at present reserved for more overt hepatic encephalopathy (eg, protein restriction, lactulose, antibiotics). Until then, you should wonder who is driving behind you....


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