Glutamine Challenge as Predictor of Hepatic Encephalopathy After Transjugular Intrahepatic Portosystemic Shunt (TIPS)

Study Overview
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Brief Summary
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Transjugular intrahepatic portosystemic shunt (TIPS) is the first-line therapy for patients with cirrhosis and refractory ascites. However, mental changes known as hepatic encephalopathy (HE) frequently occur after TIPS. There is no effective method to predict HE after TIPS. Oral glutamine challenge (OGC) and psychometric tests have been used to assess the risk for HE, but never in patients undergoing TIPS. Severe muscle loss may also predispose patients to HE. The aim of the present study is to assess if both the OGC and psychometric tests can accurately predict the development of overt HE after TIPS. Patients will be studied before TIPS and followed after TIPS for the development of HE. The role of muscle loss in favoring HE, as well as is possible reversibility after TIPS will also be investigated.

Detailed Description
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In cirrhosis, up to 10% of patients develop refractory ascites. TIPS (transjugular intrahepatic portosystemic shunt) is the first-line therapy for these patients. However, 30% will go on to develop hepatic encephalopathy (HE) as a consequence of TIPS, and there is no effective method to predict this outcome. Oral glutamine challenge (OGC) is used to functionally assess ammonia metabolism, and the severity of porto-systemic collateralization, and it has been used to predict overt HE. Psychometric tests (i.e. Psychometric Hepatic Encephalopathy Score [PHES] and inhibitory control test) allow the identification of covert forms of HE and can also predict overt HE. Severe sarcopenia may also predispose patients to HE. The aim of the present study is to assess if both the degree of impairment in ammonia metabolism as estimated with the OGC, and cognitive status as determined by psychometric tests, can accurately predict the development of overt HE after TIPS. Patients will be studied before TIPS and followed after TIPS for the development of overt HE. The role of sarcopenia in favoring HE, as well as is possible reversibility after TIPS will also be investigated.

Official Title
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Glutamine Challenge as Predictor of Hepatic Encephalopathy After Transjugular Intrahepatic Portosystemic Shunt (TIPS)

Conditions
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Cirrhosis, Refractory Ascites, Hepatic Hydrothorax, Hepatic Encephalopathy

Intervention / Treatment
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* Other: Oral glutamine challenge
* Other: Psychometric Tests


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Cirrhosis (any etiology) Refractory ascites or hepatic hydrothorax and plan for TIPS placement Exclusion Criteria: Well-documented overt hepatic encephalopathy, either persistent or at the time of screening Any contraindication for TIPS placement Except for coagulopathy and thrombocytopenia (decided on an individual basis) Uncontrolled depression/anxiety disorder or use of antipsychotic drugs Active use of alcohol or illicit drugs History of dementia TIPS planned for another indication. Active alcoholic liver disease.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| TIPS<br>Patients 18-75 year old with refractory ascites or hepatic hydrothorax and cirrhosis, eligible for TIPS placement. All patients will have a baseline oral glutamine challenge and psychometric tests. | Other: Oral glutamine challenge<br>* Blood ammonia determination before, 30-, 60-, and 90-minute, after intake of 10 g of L-glutamine<br>Other: Psychometric Tests<br>* PHES (portosystemic hepatic encephalopathy score) and ICT (inhibitory control test)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overt hepatic encephalopathy | Classified according to West Haven criteria. | up to 18 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Sarcopenia | According to CT scan L3 area of muscle mass | Baseline and 6 months post-TIPS | 
| Physical activity | Pedometer readings and physical activity questionnaire | Baseline and 6 months post-TIPS | 
| Dietary Intake | Food frequency questionnaire (FFQ, NutritionQuest, Berkeley, CA) | Baseline and 6 months post-TIPS | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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TIPS, Hepatic encephalopathy, Oral glutamine challenge, Psychometric tests, Portal hypertension, Cirrhosis