Diagnosis and Treatment of Minimal Hepatic Encephalopathy to Prevent Motor Vehicle Accidents: A Cost-Effectiveness Analysis

Minimal hepatic encephalopathy (MHE) is present in approximately 55% of cirrhotic patients tested (1-4). MHE increases the risk of development of overt hepatic encephalopathy (OHE) and adversely affects survival (5). MHE also is associated with impaired driving skills and a significantly higher risk of motor vehicle crashes (6, 7) due to the attention and visuo-motor coordination deficits associated with this condition. Driving impairment is highly correlated with diminished psychometric performance (8-10). There are several methods for the diagnosis of MHE, including a comprehensive neuropsychological exam, standard psychometric batteries, neuro-physiological testing and computerized testing (11-13). These modalities are usually copyrighted and require psychological or neurological expertise for procuring, administration and interpretation in the US, increasing associated costs and reducing access(1). An AASLD survey demonstrated that the majority of hepatologists were not able to test cirrhotic patients for MHE partly due to the lack of availability of testing techniques (14). High-sensitivity tests that can be administered by personnel without specialized expertise, such as the inhibitory control test (ICT)—offer a potentially cost-effective method for diagnosing MHE (6, 15, 16). The ICT is a computerized test of attention and response inhibition which is inexpensive and is well correlated with driving impairment (6, 9, 15). Abnormalities in ICT and standard psychometric tests have been shown to be related to driving offenses and vehicular crashes (6, 17, 18). The societal costs associated with motor vehicle accidents include productivity losses, medical expenses, motor vehicle damage, employers’ uninsured costs, and administrative expenses (19). The high cost of vehicular accidents—estimated at more than $200 billion per year in the U.S.(20)—necessitates investigation of treatable forms of driving impairment, such as MHE. Lactulose therapy has been tested extensively for patients diagnosed with MHE (13). Lactulose is inexpensive and has been shown to reverse MHE-based performance deficits on psychometric tests (10, 21, 22). However, lactulose adherence is relatively poor, in large part due to gastrointestinal adverse effects (10, 21-23). Rifaximin, which also has been used as a therapy for MHE(24-26), has a much better adherence profile. Moreover, rifaximin has been shown to improve driving simulator performance in a placebo-controlled randomized trial(25). We report here the results of a model-based cost-effectiveness of MHE diagnosis and subsequent pharmaceutical treatment (lactulose or rifaximin) to reduce motor vehicle accidents among cirrhotic patients. The analyses compared 4 potential strategies for diagnosing and treating MHEwith a no-treatment alternative. Because the effectiveness of pharmaceutical treatments with respect to reducing accidents among treated patients has not been well established, we conducted extensive sensitivity analyses around this key parameter. The aim was to provide a cost-effectiveness platform for MHE diagnosis and treatment from a societal perspective and tailored to individual treatment options available in the United States.