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Lack of patient accrual
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| Name | Class |
|---|---|
| Université de Montréal | OTHER |
| University Hospital, Geneva | OTHER |
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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| TIPS | 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. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Oral glutamine challenge | Other | Blood ammonia determination before, 30-, 60-, and 90-minute, after intake of 10 g of L-glutamine |
|
| Measure | Description | Time Frame |
|---|---|---|
| Overt hepatic encephalopathy | Classified according to West Haven criteria. | up to 18 months |
| 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 |
| Measure | Description | Time Frame |
|---|---|---|
| Skeletal muscle trophic factors | IGF-1 and myostatin levels | Baseline and 6 months post-TIPS |
| Glutaminase gene variations | 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 |
Inclusion Criteria:
Exclusion Criteria:
Well-documented overt hepatic encephalopathy, either persistent or at the time of screening
Any contraindication for TIPS placement
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.
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Consecutive patients will be recruited from the Gastroenterology / Hepatology Clinics at UAMS and other participating centers. Those fulfilling inclusion/exclusion criteria will be invited to participate.
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| Name | Affiliation | Role |
|---|---|---|
| Andres Duarte-Rojo, MD, MSc | University of Arkansas | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of Arkansas for Medical Sciences | Little Rock | Arkansas | 72205 | United States | ||
| University of Montreal |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 20581246 | Background | Rossle M, Gerbes AL. TIPS for the treatment of refractory ascites, hepatorenal syndrome and hepatic hydrothorax: a critical update. Gut. 2010 Jul;59(7):988-1000. doi: 10.1136/gut.2009.193227. | |
| 20820037 | Background | Romero-Gomez M, Jover M, Del Campo JA, Royo JL, Hoyas E, Galan JJ, Montoliu C, Baccaro E, Guevara M, Cordoba J, Soriano G, Navarro JM, Martinez-Sierra C, Grande L, Galindo A, Mira E, Manes S, Ruiz A. Variations in the promoter region of the glutaminase gene and the development of hepatic encephalopathy in patients with cirrhosis: a cohort study. Ann Intern Med. 2010 Sep 7;153(5):281-8. doi: 10.7326/0003-4819-153-5-201009070-00002. |
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Serum, plasma, and PBMCs
| Psychometric Tests | Other | PHES (portosystemic hepatic encephalopathy score) and ICT (inhibitory control test) |
|
| Baseline and 6 months post-TIPS |
| Dietary Intake | Food frequency questionnaire (FFQ, NutritionQuest, Berkeley, CA) | Baseline and 6 months post-TIPS |
| Baseline |
| Psychometric tests | Repeat PHES and ICT | 3 and 6 months post-TIPS |
| Montreal |
| Quebec |
| H2X 1P1 |
| Canada |
| University Hospitals of Geneva | Geneva | Switzerland |
| 12445419 | Background | Romero-Gomez M, Grande L, Camacho I, Benitez S, Irles JA, Castro M. Altered response to oral glutamine challenge as prognostic factor for overt episodes in patients with minimal hepatic encephalopathy. J Hepatol. 2002 Dec;37(6):781-7. doi: 10.1016/s0168-8278(02)00330-6. |
| 22151412 | Background | Ditisheim S, Giostra E, Burkhard PR, Goossens N, Mentha G, Hadengue A, Spahr L. A capillary blood ammonia bedside test following glutamine load to improve the diagnosis of hepatic encephalopathy in cirrhosis. BMC Gastroenterol. 2011 Dec 8;11:134. doi: 10.1186/1471-230X-11-134. |
| 21461913 | Background | Duarte-Rojo A, Estradas J, Hernandez-Ramos R, Ponce-de-Leon S, Cordoba J, Torre A. Validation of the psychometric hepatic encephalopathy score (PHES) for identifying patients with minimal hepatic encephalopathy. Dig Dis Sci. 2011 Oct;56(10):3014-23. doi: 10.1007/s10620-011-1684-0. Epub 2011 Apr 3. |
| 17222319 | Background | Bajaj JS, Saeian K, Verber MD, Hischke D, Hoffmann RG, Franco J, Varma RR, Rao SM. Inhibitory control test is a simple method to diagnose minimal hepatic encephalopathy and predict development of overt hepatic encephalopathy. Am J Gastroenterol. 2007 Apr;102(4):754-60. doi: 10.1111/j.1572-0241.2007.01048.x. Epub 2007 Jan 11. |
| 22740290 | Background | Tandon P, Ney M, Irwin I, Ma MM, Gramlich L, Bain VG, Esfandiari N, Baracos V, Montano-Loza AJ, Myers RP. Severe muscle depletion in patients on the liver transplant wait list: its prevalence and independent prognostic value. Liver Transpl. 2012 Oct;18(10):1209-16. doi: 10.1002/lt.23495. |
| ID | Term |
|---|---|
| D001201 | Ascites |
| D006501 | Hepatic Encephalopathy |
| D005355 | Fibrosis |
| D006975 | Hypertension, Portal |
| ID | Term |
|---|---|
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D017093 | Liver Failure |
| D048550 | Hepatic Insufficiency |
| D008107 | Liver Diseases |
| D004066 | Digestive System Diseases |
| D001928 | Brain Diseases, Metabolic |
| D001927 | Brain Diseases |
| D002493 | Central Nervous System Diseases |
| D009422 | Nervous System Diseases |
| D008659 | Metabolic Diseases |
| D009750 | Nutritional and Metabolic Diseases |
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| ID | Term |
|---|---|
| D011594 | Psychometrics |
| ID | Term |
|---|---|
| D011581 | Psychological Tests |
| D004191 | Behavioral Disciplines and Activities |
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