Human error is the number one cause of car accidents and has been the leading culprit in up to 71% of crashes.1 Societies have legislated against two main factors influencing the likelihood of driver's error: speeding and alcohol consumption. Awareness of the link between some medical conditions (e.g., dementia, cardiac disease, diabetes, stroke, or epilepsy) and car accidents2 highlights the issue of how to assess medical fitness to drive.3 Some states in the U.S. require physicians to report to the local licensing authority patients whose medical conditions might affect their driving ability. In this issue of HEPATOLOGY, Wein and colleagues report impaired fitness to drive in patients with cirrhosis and minimal hepatic encephalopathy.4 This study highlights the importance of minimal hepatic encephalopathy, a condition usually neglected because it is purportedly subclinical or represents only a latent or early form of symptomatic hepatic encephalopathy.5

Minimal hepatic encephalopathy is viewed as a mild neurocognitive disorder present in patients with cirrhosis.6 Individuals with this condition have cognitive deficits that affect mostly attention, speed of information processing and motor abilities,7 a pattern that suggests “subcortical” brain involvement.8 The level of cognitive impairment is so minimal that it is not recognized in a standard neurologic exam. The diagnosis requires corroboration of cognitive deficits using additional tests. However, the diagnosis of minimal hepatic encephalopathy has become a permanent source of discussion.9 Neurophysiologic tests (e.g., spectral electroencephalogram, evoked potentials) have been advocated as more sensitive than psychometric tests.10 However, these methods assess different aspects of the whole picture: a spectrum of neurologic abnormalities secondary to portal-systemic shunting.

As a result of the myriad neurologic manifestations, a consensus conference proposed a large study to redefine neuropsychiatric abnormalities in liver disease.6 Hepatic encephalopathy would be considered a continuous dimension that could be measured with one index that would summarize several neurologic domains, such as cognition, behavior, or biologic rhythms. Minimal hepatic encephalopathy would be the mildest form of hepatic encephalopathy and would be diagnosed on the basis of certain cut-off values. Until this study is carried out (if ever!), the best characterization of minimal hepatic encephalopathy can be obtained through neuropsychologic measures,11 which also allow for a better estimation of the possible implications of such deficits on daily living.

Could the repercussions of minimal hepatic encephalopathy be similar to those described for other mild neurocognitive disorders, such as early Alzheimer's disease?12 In fact, assessment of its implications is confounded by many factors. Cirrhosis causes a decrease in health-related quality of life that is associated with the severity of liver failure13 and might be better explained by its effects on nutritional status.14 In addition, alcohol consumption—one of the most frequent causes of cirrhosis—can cause direct effects on cognitive function. The neuropsychologic impairment of minimal hepatic encephalopathy is sufficiently mild15 that effects on instrumental activities (e.g., shopping, answering the phone, taking public transportation) or basic activities of daily life (e.g., dressing, personal hygiene, eating) are not expected. However, the impairment of attention, executive function, and psychomotor skills may impair complex activities such as planning a trip, handling finances, gardening, performing a job, or driving a car. There is some evidence that this may be the case. In a prior study in 179 outpatients with cirrhosis, the Sickness Impact Profile questionnaire detected more frequent impairment in daily life activities related to alertness, social interactions, recreation, or work among those with minimal hepatic encephalopathy, an effect that was maintained after adjusting for the severity of liver failure.16

A decline in cognitive function increases the risk for automobile crashes.3 The impairment of attention and speed of mental processing—both of which are characteristic of minimal hepatic encephalopathy—affects an individual's ability to react to unexpected traffic conditions, such as an illegal incursion by another vehicle at an intersection.17 For this reason, based on the responses to extensive batteries of neuropsychologic tests, two studies18, 19 considered a large proportion of patients with cirrhosis (44%–60%) unfit to drive. However, a pilot study that evaluated driving on a real road test in 15 cirrhotics (nine with minimal hepatic encephalopathy) failed to detect impaired driver performance.20 These results underline the importance of testing driving ability rather than relying on neuropsychologic tests or driving simulators. Nevertheless, as the authors acknowledged, to reach firm conclusions it is necessary to assess larger groups of patients and perform studies in other countries where different driving rules may apply.

Wein and colleagues report the results of a driving study in Germany.4 They evaluated 48 subjects with cirrhosis, 14 of whom had minimal hepatic encephalopathy, using a standardized 90-minute on-the-road driving test. Driving abilities were compared with a control group of 50 subjects at a stable phase of chronic gastroenterologic disease to adjust for the possible effects of chronic illness. A professional driving instructor, unaware of the diagnosis, scored driving competence. The main finding of the study is that ratings were worst in patients with minimal hepatic encephalopathy, while subjects without cognitive impairment scored similar to controls. Risks of impaired fitness could also be extrapolated by the observation that the instructor had to intervene more frequently during the test to avoid accidents in patients with minimal hepatic encephalopathy (36%) than in nonaffected subjects with cirrhosis (6%) or controls (8%). The discrepancies with the study of Srivastava and colleagues20 could be explained by (1) the assessment of a larger sample of patients, (2) a cohort likely to exhibit a more advanced cognitive impairment (most of them had experienced prior episodes of encephalopathy), and (3) a more demanding driving test (22 miles). Unfortunately, the authors do not explain whether such a degree of driving impairment would cancel the driver's license in Germany.

The results of Wein's study suggest that minimal hepatic encephalopathy should be considered a medical condition that increases the risks for automobile crashes. However, crash statistics have not yet detected over-involvement of patients with cirrhosis. Furthermore, large epidemiologic studies have challenged the notion of driving risks in other diseases that were considered dangerous.21 This does not mitigate the potential risks of minimal hepatic encephalopathy but defines the need for definitive studies in this area. It would be very helpful to examine the frequency of accidents in patients with cirrhosis and investigate their relationship with cognitive function. Institutions performing liver transplants have an optimal opportunity to perform such a study that by necessity would be collaborative and which could be extended to the posttransplant period.

Should health care providers recommend driving restrictions for patients with minimal hepatic encephalopathy? It seems reasonable to restrict driving in patients with chronic hepatic encephalopathy, where the clinical examination raises concerns with potential loss of driving skills or where personal history suggests a higher risk for sudden episodes of loss of consciousness. However, this safeguard cannot be extended to the entire spectrum of minimal hepatic encephalopathy. First, as discussed before, the diagnosis of minimal hepatic encephalopathy is still controversial. Second, as observed in dementia2 and corroborated by Srivastava and colleagues,20 a modest cognitive loss does not necessarily affect an individual's driving skills. A consensus has emerged to preclude driving in moderate to severe dementia.22 However, early Alzheimer's disease requires specialized assessment for driving competence. Similarly, in the absence of clear-cut criteria, assessment of fitness to drive in minimal hepatic encephalopathy requires an individualized approach.

In practice, there are several steps that may be followed. The diagnosis of cirrhosis prompts a series of screening procedures, such as ultrasonography for hepatocellular carcinoma or upper endoscopy for varices. Similarly, patients with cirrhosis who drive a car should undergo screening for minimal hepatic encephalopathy. This screening is probably critical for those at higher risk for cognitive impairment: patients with advanced cirrhosis (Child B–C), large portal-systemic shunts (transjugular intrahepatic portosystemic shunts [TIPS], surgery), or prior episodes of encephalopathy. A well-validated and practical screening test for minimal hepatic encephalopathy is not available; however, several diagnostics tools still under clinical evaluation appear to be promising candidates.11, 23 Meanwhile, the best option is to use a combination of simple psychometric tests under the supervision of a neuropsychologist. This combination may include the Symbol Digit test, the Trail Making test (A and B), and a computerized visual reaction time test, because these tests assess attention and speed of mental processing, both of which are relevant for driving. Specialized assessment of fitness to drive, including a driving test on the road, should be considered for those with abnormal results in psychometric tests. Unfortunately, there are no standard rules on how this assessment should be performed, and the legislation varies in each country. It may be prudent to restrict driving in individuals with conspicuous neuropsychologic impairment, especially if relatives have observed a decline in driving abilities. A graded approach, restricting driving to daytime hours and short distances, may be adequate for those with mild neuropsychologic impairment and good driving reports from relatives.

On November 19, 2002, John P. Walters, Director of the National Drug Control Policy, made the following statement in a White House Press Release:

“We have solid data regarding the prevalence and seriousness of impaired driving. America already loses too many lives to drivers who are under the influence of alcohol; we cannot allow a lack of public awareness to contribute to the deaths of more innocent motorists.”

Public awareness is indeed necessary to protect third parties against those who drive under the influence of conditions that impair their mental state. During recent years a huge effort has been devoted to understand the pathophysiological processes that lead to cirrhosis and its impact on the cardiocirculatory and respiratory systems as well as renal and neurologic function. However, only a small part of the research has been dedicated to the impact on the daily lives of these patients. One of the main values of the study by Wein and colleagues is that it shifts the focus to the patient's actual life. Our priority should be to better define minimal hepatic encephalopathy and develop tools that can be easily applied to identify patients at higher risk for car accidents. The possible benefits of treatments for minimal hepatic encephalopathy on the ability to drive should be determined. Until we achieve these goals, the recommendation for patients who may be driving under the influence of minimal hepatic encephalopathy is to undergo neuropsychologic screening, followed by specialized assessment of fitness to drive if this is abnormal. Protecting our patients against car accidents has effects beyond their own health.


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  2. Acknowledgements

We are indebted to Dr. Carlos Jacas, neuropsychologist, for his critical review of the manuscript and helpful discussions.


  1. Top of page
  2. Acknowledgements