Diagnosis of Covert/Minimal Hepatic Encephalopathy by Means of Continuous Reaction Time Measurement
Diagnosis of Covert/Minimal Hepatic Encephalopathy by Means of Continuous Reaction Time Measurement
The investigators wish to investigate how the Continuous Reaction Time (CRT) method can be
 used in the diagnosis and monitoring of covert hepatic encephalopathy (cHE)in patients with
 cirrhosis of the liver. The hypothesis is that the CRT method (duration 10-2 minutes) can
 serve as a tool in the diagnosis and monitoring of cHE and is an alternative to using the
 Portosystemic Encephalopathy Test (PSE)(duration 20-25 minutes).
Objective: The aim of this project is to investigate whether continuous reaction time
 measurements (CRT) are suitable as a screening and monitoring tool for covert hepatic
 encephalopathy (c/mHE).

 Method:

 Sub-protocol 1: As a part of this PhD protocol 100 healthy individuals and 50 with chronic
 disease (not liver cirrhosis) will be tested using the CRT and PSE tests. This is to
 determine the normal range for the PSE test in the Danish population.

 Sub-protocol 2: A total of 120 (aprox. 145 to adjust for drop outs) patients with liver
 cirrhosis from two Danish hospitals will be examined with both CRT and with the test that is
 the closest we get to a gold standard, namely portosystemic encephalopathy test (PSE). We
 wish to examine if the CRT test agrees with the PSE test, which may be to time consuming to
 perform in everyday clinical practice, and with quality of life scores (SF-36 and Sickness
 Impact Profile). The relationship between the CRT and PSE test and various blood tests and
 the Charlston co-morbidity score will also be examined.

 Sub-protocol 3: Forty-four of the 120 included patients will, regardless of CRT test result,
 be randomized to treatment with lactulose, rifaximin and branched chain amino acids (BCAA) or
 placebo lactulose, rifaximin and BCAA. This is to evaluate whether the CRT method is able to
 detect a response to treatment, and see if changes in psychometric tests (PSE and CRT) are in
 accordance with quality of life scores and predicts subsequent development of overt hepatic
 encephalopathy.

 Perspective: CRT method should, if it proves good enough, continue to be the Danish test of
 choice and hopefully be more widely used in our country. The validation of tests for the
 diagnosis of covert hepatic encephalopathy will give cirrhotic patients with covert hepatic
 encephalopathy and reduced quality of life the best opportunity to be diagnosed and offered
 appropriate treatment. If the CRT method is not able to identify a population that benefits
 from anti-encephalopathy treatment other screening and monitoring tests should be used.
Inclusion Criteria:

 For healthy volunteers:

 -  Age> 18 years

 -  Written informed consent

 -  Speak and understand Danish

 For patients:

 -  Age > 18 years

 -  Liver cirrhosis confirmed by biopsy or appropriate clinic and biochemistry, and
 imaging.

 -  Written informed consent

 -  Speak and understand Danish

 Exclusion Criteria (patients and control persons):

 -  Clinical manifest hepatic encephalopathy

 -  Consumption of psychoactive substances within 6 days of test

 -  Organic brain disease (i.e. prior stroke, dementia)

 -  Hypothyroidism

 -  Renal failure (creatinine> 150 mg / dL)

 -  Hyponatremia (Na <125 mmol / L)

 -  Sepsis or bleeding within one week prior to testing.

 -  Serious sleep disorders

 -  Current treatment with lactulose, rifaximin or BCAA