Detection and treatment for hepatic encephalopathy prevents car accidents, reduces costs
David Cohen, M.D.·Published 29 March 2012·9 min read
Key points
A late stage liver condition, known as minimal hepatic encephalopathy (MHE), is associated with impaired driving skills and greater risk of motor vehicle accidents.
Minimal hepatic encephalopathy: a vehicle for accidents and traffic violations.
The approach to the patient with hepatic encephalopathy depends upon the severity of mental status changes and upon the certainty of the diagnosis.
Hepatology is the premier publication in the field of liver disease, publishing original, peer-reviewed articles concerning all aspects of liver structure, function and disease.
A late stage liver condition, known as minimal hepatic encephalopathy (MHE), is associated with impaired driving skills and greater risk of motor vehicle accidents. Cost analysis of management strategies for detection and treatment of MHE are published in the April issue of Hepatology, a journal of the American Association for the Study of Liver Diseases. Findings report that MHE diagnosis using the inhibitory control test followed by treatment with lactulose was the most cost-effective approach - preventing the most car accidents and reducing societal cost by up to $3.6 million over a 5-year period.
In cirrhosis, as the liver fails, the build-up of toxic substances normally removed by the liver can lead to MHE - a reversible condition that causes cognitive impairment and loss of consciousness. Medical evidence reports that MHE is present in 55% of cirrhotic patients tested, and is associated with higher risk of motor vehicle collisions due to attention and visuomotor coordination deficits. The Inhibitory control test measures an individual's attention and experts suggest it could be cost-effective in diagnosing MHE and correlates with driving impairments.
Previous research estimates vehicular accidents cost more than $200 billion per year in the U.S. in terms of lost productivity, medical costs, automobile damage, and insurance expenses. "Detection and treatment of MHE has potential to reduce costs and morbidity related to car accidents," explains lead study author Dr. Jasmohan Bajaj with McGuire VA Medical Center and Associate Professor at Virginia Commonwealth University School of Medicine. "Our study analyzes the cost-effectiveness of various strategies for diagnosing and treating MHE to reduce vehicular accidents and the societal cost burden."
Researchers compared five strategies for managing MHE that included presumptive treatment of all cirrhotic patients; diagnosis by neuropsychological exam with therapy; psychometric diagnostic testing with treatment; diagnosis using inhibitory control test with treatment; and no MHE diagnostics or treatment. Analysis was conducted on a simulated group of 1,000 cirrhotic patients treated for MHE with lactulose or rifaximin, and followed for 5 years. Researchers estimated the societal cost of a single car accident to be $42,100.
Results show the cost per motor vehicle accident prevented by diagnosing MHE with the inhibitory control test was $24,454; standard psychometric tests was $25,470; with presumptive treatment it was $30,469; and with neuropsychological exam the cost was $33,742. "Our findings provide strong evidence that detection of MHE, particularly the inhibitory control test, and subsequent treatment with lactulose reduces societal costs by preventing motor vehicle accidents in patients with MHE," concludes Dr. Bajaj.
Minimal hepatic encephalopathy (MHE) is the mildest form of spectrum of hepatic encephalopathy (HE).
Patients with MHE have no recognizable clinical symptoms of HE but have . The prevalence of MHE is high in patients with cirrhosis of liver and varies between 30% and 84%; it is higher in patients with poor liver function.
Written and revised by
David Cohen, M.D.
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The diagnostic criteria for MHE have not been standardized but rest on careful patient history and physical examination, normal mental status examination, demonstration of abnormalities in cognition and/or neurophysiological function, and exclusion of concomitant neurological disorders. MHE is associated with impaired health-related quality of life, predicts the development of overt HE and is associated with poor survival. Hence, screening all patients with cirrhosis for MHE using psychometric tests, and treatment of those patients diagnosed to have MHE has been recommended. Ammonia plays a key role in the pathogenesis of MHE, which is thought to be similar to that of overt HE. Thus, ammonia-lowering agents such as lactulose and probiotics have been tried. These agents have been shown to improve cognitive and psychometric deficits, and have good safety profile. Future studies will better define the role of other drugs, such as rifaximin, acetyl L-carnitine and L-ornithine L-aspartate.
The authors of a related editorial also published in this month's issue cite previous research that reports driving errors account for 71% to 98% of all motor vehicle accidents. They suggest that the high percentage of traffic accidents involving driver error makes the assessment of driving abilities crucial for patients with MHE. The study by Bajaj et al. provides evidence which may encourage further real-life effect of MHE on accident rates, and according to the authors, raise awareness of the implications for patients with liver disease and the whole of society.
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.
References
1. Bajaj JS, Hafeezullah M, Hoffmann RG, Saeian K. Minimal hepatic encephalopathy: a vehicle for accidents and traffic violations. Am J Gastroenterol. 2007;102:1903-1909. 2. Ferenci P, Lockwood A, Mullen K, Tarter R, Weissenborn K, Blei AT. Hepatic encephalopathy - definition, nomenclature, diagnosis, and quantification: final report of the working party at the 11th World Congresses of Gastroenterology, Vienna, 1998. Hepatology. 2002;35:716-721.
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Full Citations: "Diagnosis and Treatment of Minimal Hepatic Encephalopathy to Prevent Motor Vehicle Accidents: A Cost-Effectiveness Analysis." Jasmohan S. Bajaj, Steven D. Pinkerton, Arun J. Sanyal, Douglas M. Heuman. Hepatology; December 2, 2011 (DOI: 10.1002/hep.25507); Print Issue Date: April 2012. http://onlinelibrary.wiley.com/doi/10.1002/hep.25507/abstract.
Management of Hepatic Encephalopathy
The approach to the patient with hepatic encephalopathy depends upon the severity of mental status changes and upon the certainty of the diagnosis. As an example, a patient with known cirrhosis and mild complaints of decreased concentration might be served best by an empiric trial of rifaximin or lactulose and a follow-up office visit to check its effect. However, the patient presenting in hepatic coma requires a different approach. General management recommendations include the following:
- Exclude nonhepatic causes of altered mental function. - Consider checking an arterial ammonia level in the initial assessment of a hospitalized patient with cirrhosis and with impaired mental function. Ammonia levels have less use in a stable outpatient. - Precipitants of hepatic encephalopathy, such as metabolic disturbances, gastrointestinal bleeding, infection, and constipation, should be corrected. - Avoid medications that depress central nervous system function, especially benzodiazepines. Patients with severe agitation and hepatic encephalopathy may receive haloperidol as a sedative. Treating patients who present with coexisting alcohol withdrawal and hepatic encephalopathy is particularly challenging. These patients may require therapy with benzodiazepines in conjunction with lactulose and other medical therapies for hepatic encephalopathy. - Patients with severe encephalopathy (ie, grade 3 or 4) who are at risk for aspiration should undergo prophylactic endotracheal intubation. They are optimally managed in the intensive care unit. - Fanelli et al investigated the efficacy of using an hourglass-shaped expanded polytetrafluoroethylene (ePTFE) stent-graft to treat patients whose hepatic encephalopathy was refractory to conventional medical therapy. In the study, 12 patients who, subsequent to receiving a transjugular intrahepatic portosystemic shunt, had developed refractory hepatic encephalopathy underwent shunt reduction with the stent-graft. - The reduction procedure immediately produced a portosystemic gradient increase in the above study's patients, who, within 18-26 hours after insertion of the stent-graft, no longer exhibited symptoms of hepatic encephalopathy. The condition did not recur over a mean follow-up period of 74 weeks. Over the course of the study, 4 patients died of cardiovascular failure, another underwent orthotopic liver transplantation, and 2 more were lost to follow-up. The 5 remaining patients finished the study in good clinical condition. The authors concluded that hourglass-shaped ePTFE stent-grafts appear to effectively reduce shunt flow and quickly improve patients’ clinical conditions.
Most current therapies are designed to treat the hyperammonemia that is a hallmark of most cases of hepatic encephalopathy.
Editorial: "Attention: Minimal Hepatic Encephalopathy and Road Accidents." Piero Amodio, Sara Montagnese, Carlo Merkel. Hepatology; January 11, 2012 (DOI: 10.1002/hep.25583); Print Issue Date: April 2012. http://onlinelibrary.wiley.com/doi/10.1002/hep.25583/abstract.
Author Contact: To arrange an interview with Dr.Bajaj, please contact Sathya Achia Abraham with Virginia Commonwealth University/VCU Medical Center sbachia@vcu.edu or 804-827-0890.
These studies are published in Hepatology. Media wishing to receive a PDF of the articles may contact healthnews@wiley.com.
About the Journal
Hepatology is the premier publication in the field of liver disease, publishing original, peer-reviewed articles concerning all aspects of liver structure, function and disease. Hepatology's current impact factor is 10.885.Each month, the distinguished Editorial Board monitors and selects only the best articles on subjects such as immunology, chronic hepatitis, viral hepatitis, cirrhosis, genetic and metabolic liver diseases and their complications, liver cancer, and drug metabolism. Hepatology is published on behalf of the American Association for the Study of Liver Diseases (AASLD).
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