Minimal Encephalopathy/Rifaximin

AASLD: Antibiotic Reverses Cognition Loss in MHE
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BOSTON -- In patients with minimal hepatic encephalopathy, an antibiotic appears to reverse difficulties in driving a car associated with the condition, a researcher said here.

Rifaximin (Xifaxan) is most commonly used to treat travelers' diarrhea, but it is also approved for minimal hepatic encephalopathy, according to Jasmohan Bajaj, MD, of Virginia Commonwealth University Medical Center in Richmond, Va.

In a randomized, placebo-controlled, double-blind trial, patients taking the drug did better on simulated driving tasks than those given placebo, Bajaj reported at the annual meeting of the American Association for the Study of Liver Diseases.

Action Points  

    * Note that this study was published as an abstract and presented at a conference. These data and conclusions should be considered to be preliminary until published in a peer-reviewed journal.


    * Note that the gastrointestinal tract is the primary source of ammonia, the presumed mediator of hepatic encephalopathy, and rifaximin is thought to lower blood ammonia levels by reducing ammonia production and absorption.

Minimal encephalopathy does not lead to overt cognitive dysfunction, but can be shown to exist with neuropsychological tests. It impairs quality of life and has been shown to increase the risk of traffic accidents.

The importance of the study, Bajaj said, is that "it's the first time a cognitive change has resulted in a real-life outcome."

He and his colleagues enrolled 41 patients -- all current drivers -- with minimal hepatic encephalopathy confirmed by a battery of five cognitive tests.

At baseline, the patients were tested using a simulator for driving and navigation skills, with the outcomes being such things as collisions, speeding tickets, and illegal turns, Bajaj said. At the same time, they were given cognitive tests, quality of life was measured using the Sickness Impact Profile, venous ammonia levels were measured, and they were graded on the Model for End-Stage Liver Disease (MELD) score.

The patients were randomly assigned to get rifaximin (at 550 mg a day) or placebo for 30 days, at the end of which time they returned for adherence testing and were given another 30 days of study drug, Bajaj said.

At the end of the eight-week study period, the baseline tests were repeated, including those in the simulator. The primary outcomes were improvements in the driving measures -- speeding, illegal turns, and collisions. Changes in cognition and quality of life were secondary outcomes.

The researchers found:

    * 76% of those getting the drug had fewer total driving errors, compared with 33% of those on placebo (P=0.013)
    * 81% of those on the drug had fewer speeding tickets, compared with 33% of those on placebo (P=0.005)
    * 62% of those on rifaximin had fewer illegal turns, compared with 19% of those on placebo (P=0.012)
    * There was no significant difference in the number of collisions

Participants on rifaximin also had a significantly better increase in cognition and on the psychosocial elements of the Sickness Impact Profile, Bajaj reported.

He said the goal was to increase insight into driving errors, which was best measured by such subtle factors as illegal turns and speeding tickets. In the simulator, he said, a collision stopped the game, with a loud crash, which allowed patients in both groups to gain the same insight.

"Tickets and illegal turns do not come with anything, so the patients have to themselves realize they've gone off," he said.

The findings are important because they appear to demonstrate that some of the cognitive effects of minimal hepatic encephalopathy can be turned back by medication, according to Kevin Mullen, MD, of MetroHealth Medical Center in Cleveland, who moderated the session at which the data were presented.

"Up to now, no one had ever shown reversibility of those driving problems," he told MedPage Today.

Other papers presented at the session, he noted, suggested that the drug could improve survival and slow progression of the disease. But those effects -- as well as the possible cognitive benefits -- are "still up in the air" and need more study.

The study was supported by the NIH and Salix.

Bajaj reported financial links with Salix and Ocera Therapeutics.

Mullen reported financial links with Salix, Ocera, Hyperion, Hoffman LaRoche, and CLDG.

Primary source: American Association for the Study of Liver Diseases
Source reference:
Bajaj JS, et al "Rifaximin improves driving simulator performance in minimal hepatic encephalopathy: A double - blind, placebo - controlled, prospective randomized trial" AASLD 2010; Abstract 22

http://www.medpagetoday.com/MeetingCoverage/AASLD/23080?utm_content=GroupCL&utm_medium=email&impressionId=1288682721395&utm_campaign=DailyHeadlines&utm_source=mSpoke&userid=235671

[Bill1954]

Interesting, Michael. I understand this is a relatively expensive drug; if it becomes officially labeled for HE, maybe insurance will be more likely to cover the costs involved. I suppose studies like this are a step in that direction.

Thanks for posting,

Bill

[HectorSF]

Yes, rifaximin (Xifaxan - Salix) has really helped me. Not only does it reduce the symptoms of HE but patients treated with rifaximin also required less hospitalization, had shorter duration of hospitalization, and lower hospital charges compared with lactulose-treated patients. Although it is commonly prescribed to be taken along with latulose.

March 2010, rifaximin was approved by the FDA to reduce recurrence of hepatic encephalopathy.

I just got my script filled at Walgreens. 90 - 200mg pills cost $816.89. My co-pay was $45.

HE info:

Grading of the symptoms of hepatic encephalopathy is performed according to the so-called West Haven classification system

    * Grade 0 - Minimal hepatic encephalopathy (previously known as subclinical hepatic encephalopathy). Lack of detectable changes in personality or behavior. Minimal changes in memory, concentration, intellectual function, and coordination. Asterixis is absent.
    * Grade 1 - Trivial lack of awareness. Shortened attention span. Impaired addition or subtraction. Hypersomnia, insomnia, or inversion of sleep pattern. Euphoria, depression, or irritability. Mild confusion. Slowing of ability to perform mental tasks. Asterixis (hand flapping) can be detected.
    * Grade 2 - Lethargy or apathy. Disorientation. Inappropriate behavior. Slurred speech. Obvious asterixis . Drowsiness, lethargy, gross deficits in ability to perform mental tasks, obvious personality changes, inappropriate behavior, and intermittent disorientation, usually regarding time.
    * Grade 3 - Somnolent but can be aroused, unable to perform mental tasks, disorientation about time and place, marked confusion, amnesia, occasional fits of rage, present but incomprehensible speech
    * Grade 4 - Coma with or without response to painful stimuli

In minimal hepatic encephalopathy, patients may have normal abilities in the areas of memory, language, construction, and pure motor skills. However, patients with minimal hepatic encephalopathy demonstrate impaired complex and sustained attention. They may have delays in choice reaction time. They may even have impaired fitness to drive.

Patients with mild and moderate hepatic encephalopathy demonstrate decreased short-term memory and concentration upon mental status testing. They may show signs of asterixis, flapping tremor of the hands.

Some patients show evidence of fetor hepaticus, a sweet musty aroma of the breath that is believed to be secondary to the exhalation of mercaptans.

Other potential physical examination findings include hyperventilation and decreased body temperature.

Hectorsf

[mikesimon]

That's really wonderful that the drug is helping you.
I think about you often. And I have the highest of hopes for you.

Be well,
Mike

[eureka254]

The potential that it not only stops HE but can reverse it as well is very encouraging.  Hopefully this is the first of more such research to come.  Thanks for posting the article.

HectorSF:
Great to hear first-hand that the Rifaximin is doing you good!  Do you find it has any significant side effects for you?  I hope only good ones...

[ClippedWings]

I'm glad the Rifaximin is working for you.  It did little to reduce my symptoms of HE and I was hospitalized several times for HE prior to my transplant.  I was sure hoping the Rifaximin would do the trick because it is a much more pleasant drug to take compared to Lactulose as I'm sure you well know.  I personally never noticed any side effects from Rifaximin. Rifaximin in conjunction with heavy doses of Lactulose was the only way I ever came out of my bouts of HE.   Hope you stay well.
Bill