Cirrhosis, Hepatic Encephalopathy, Hepatic Hydrothorax, Refractory Ascites
Conditions
Keywords
TIPS, Hepatic encephalopathy, Oral glutamine challenge, Psychometric tests, Portal hypertension, Cirrhosis
Brief summary
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
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.
Interventions
OTHEROral glutamine challenge
Blood ammonia determination before, 30-, 60-, and 90-minute, after intake of 10 g of L-glutamine
OTHERPsychometric Tests
PHES (portosystemic hepatic encephalopathy score) and ICT (inhibitory control test)
Sponsors
Université de Montréal
University Hospital, Geneva
University of Arkansas
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Overt hepatic encephalopathy | up to 18 months | Classified according to West Haven criteria. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Sarcopenia | Baseline and 6 months post-TIPS | According to CT scan L3 area of muscle mass |
| Physical activity | Baseline and 6 months post-TIPS | Pedometer readings and physical activity questionnaire |
| Dietary Intake | Baseline and 6 months post-TIPS | Food frequency questionnaire (FFQ, NutritionQuest, Berkeley, CA) |
Other
| Measure | Time frame | Description |
|---|---|---|
| Glutaminase gene variations | Baseline | Genetic variations in the glutaminase gene (located at 2q-32-134) consisting of single nucleotide polymorphisms (SNPs) identifying a microsatellite of GCA repeats in the 5' untranslated region |
| Psychometric tests | 3 and 6 months post-TIPS | Repeat PHES and ICT |
| Skeletal muscle trophic factors | Baseline and 6 months post-TIPS | IGF-1 and myostatin levels |
Countries
Canada, Switzerland, United States
Outcome results
None listed