Cerebrovascular Reactivity in Hepatic Encephalopathy

Study Overview
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Brief Summary
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It has been observed that patients with cirrhosis present a generalized state of vasoconstriction as an homeostatic response to splanchnic arteriolar vasodilatation. On progression of the disease, vascular regulation is mismatched, causing altered systemic blood flow and lose in the cerebrovascular reactivity. The investigators hypothesize that the altered cerebrovascular reactivity induces neurological disturbances related to hepatic encephalopathy and, therefore, the existence of a correlation between cerebrovascular reactivity and the stage of hepatic encephalopathy.

Detailed Description
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There is no bibliography that evidenciates a correlation between cerebrovascular reactivity and the stage of hepatic encephalopathy. There are however, papers that reveal generalized systemic vasoconstriction in patients with cirrhosis and others that affirm the presence of vascular disregulation and altered reactivity in the Middle Cerebral Artery in cirrhotic patients. In the other hand, there is published data that correlates the neurological manifestations of diseases characterised by altered blood flow and cerebrovascular reactivity with the degree of the vascular disregulation itself, identified by US Doppler. However, there are no studies correlating transcranial US Doppler findings of cerebrovascular reactivity and hepatic encephalopathy in patients with cirrhosis. Giving its importance to the chance of revealing a new way of pathophysiology and therefore, early therapeutic management.

Official Title
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Correlation Between Cerebrovascular Reactivity and Hepatic Encephalopathy in Patients With Cirrhosis

Conditions
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Hepatic Encephalopathy

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Clinical diagnosis of Liver Cirrhosis Exclusion Criteria: Personal history of surgery in the last 4 weeks Diagnosis of Diabetes Mellitus, Hypertension, COPD or liver metabolic diseases (Wilson's disease and hemochromatosis) Personal history of stroke and/or cancer Use of neuropsychiatric drugs Neuropsychiatric disorders (Schizophrenia, bipolar disorder, dementia and Attention-deficit hyperactivity disorder) Thyroid disorders without replacement therapy Hepatic or renal transplant Alcoholism with active ingest of alcohol in the last 6 months Pregnancy Labour turn-overs

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 69 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Cirrhosis, w/o hepatic encephalopathy<br>Patients with liver cirrhosis without hepatic encephalopathy by clinical (West-Haven), neurophysiological tests (PHES) nor Critical Flicker Frequency evidence. | |
| Cirrhosis-minimal hepatic encephalopathy<br>Patients with cirrhosis, without clinical evidence of hepatic encephalopathy (West Haven 0) and with positive tests for both, PHES and CFF. | |
| Cirrhosis, Hepatic encephalopathy I<br>Patients with cirrhosis and clinical evidence of hepatic encephalopathy with a West Haven score of I. | |
| Control<br>Healthy subjects willing to participate in the study | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Impaired cerebrovascular reactivity identified with transcranial Doppler ultrasonography of the Media Cerebral Artery. | Recruitment period is planned for the first 3 months of the study, where outcome messures will be evaluated in a single and unique ocassion, at the time of subject enrollment, due to the characteristics of the study (cross-sectional). | At time of recruitment (first 3 months) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Minimal Hepatic encephalopathy identified with psychometric hepatic encephalopathy score (PHES) and Critical Flicker Frequency (CFF). | Recruitment period is planned for the first 3 months of the study, where outcome messures will be evaluated in a single and unique ocassion, at the time of subject enrollment, due to the characteristics of the study (cross-sectional). | At time of recruitment (first 3 months) | 
| Hepatic encephalopathy stage I identified clinically and PHES and CFF. | Recruitment period is planned for the first 3 months of the study, where outcome messures will be evaluated in a single and unique ocassion, at the time of subject enrollment, due to the characteristics of the study (cross-sectional). | At time of recruitment (first 3 motnhs) | 
| Blood samples to measure ammonium, , renin-angiotensin-aldosterone system, endotoxemia and Sb100 | Recruitment period is planned for the first 3 months of the study, where outcome messures will be evaluated in a single and unique ocassion, at the time of subject enrollment, due to the characteristics of the study (cross-sectional). | At time of recruitment (3 months) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Hepatic Encephalopathy, Psychometric Hepatic Encephalopathy Score, Critical Flicker Frequency, Cerebrovascular Reactivity, Endotoxemia, Transcranial Doppler, Liver Cirrhosis