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| Name | Class |
|---|---|
| Swiss National Science Foundation | OTHER |
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This study is to investigate MER receptor tyrosine kinase (MERTK) signalling cascade on monocytes and tissue macrophages in respect to innate immune function of the cells in patients with cirrhosis at different stages of disease (Child A, B, C, acute decompensation, acute-on-chronic liver failure (ACLF)) and in comparison to patients with acute liver failure and to healthy controls.
MER receptor tyrosine kinase (MERTK) signalling cascade becomes activated on monocytes/macrophages during disease progression of liver cirrhosis from Child Pugh A to B/C, corresponding to early stages of decompensation, and before the receptor expression is increased. Factors involved in activation of the MERTK signalling cascade might be microbial products such as bacterial deoxyribonucleic acid (DNA) and other toll-like receptor (TLR)-ligands, MERTK ligands and cytokines, as shown elevated in cirrhotic patients.
Given the observation that MERTK levels peak on the day of admission with organ failure and decrease in patients surviving the episode of acute-on-chronic liver failure (ACLF), MERTK Inhibition at a time during progression of cirrhosis but before manifestation of acute decompensation with no cirrhosis (AD) or ACLF might prevent infectious complications, decompensation and improve survival in patients with cirrhosis.
This study is to investigate MER receptor tyrosine kinase (MERTK) signalling cascade on monocytes and tissue macrophages in respect to innate immune function of the cells in patients with cirrhosis at different stages of disease (Child A, B, C, acute decompensation, acute-on-chronic liver failure (ACLF)) and in comparison to patients with acute liver failure and to healthy controls.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| cirrhosis of the liver, stadium Child A | sampling of biological material and health related data collection longitudinally in 6-monthly intervals up to 36 months |
| |
| cirrhosis of the liver, stadium Child B | sampling of biological material and health related data collection longitudinally in 6-monthly intervals up to 36 months |
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| cirrhosis of the liver, stadium Child C | sampling of biological material and health related data collection longitudinally in 6-monthly intervals up to 36 months |
| |
| cirrhosis of the liver, acutely decompensated | sampling of biological material and health related data collection on days 1 (Baseline), 3, 7, and 14. If acutely decompensated patients re-compensate they will be followed 6-monthly for up to 36 months |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| blood sampling for research purpose | Other | blood sampling for research purpose (about 30ml) taken by venepuncture or from intravenous catheters if already in place |
|
| Measure | Description | Time Frame |
|---|---|---|
| Change in MERTK signalling cascade on monocytes | Change in MERTK signalling cascade on monocytes in respect to innate immune function of the cells in patients with cirrhosis at different stages of disease (Child A, B, C, acute decompensation, ACLF) and in comparison to patients with acute liver failure and to healthy controls | days 1 (Baseline), 3, 7, and 14; then followed 6-monthly for up to 36 months |
| Change in MERTK signalling cascade on tissue macrophages | Change in MERTK signalling cascade on tissue macrophages in respect to innate immune function of the cells in patients with cirrhosis at different stages of disease (Child A, B, C, acute decompensation, ACLF) and in comparison to patients with acute liver failure and to healthy controls | days 1 (Baseline), 3, 7, and 14; then followed 6-monthly for up to 36 months |
| Measure | Description | Time Frame |
|---|---|---|
| Change in mechanism of MERTK activation in cell culture models using monocytes | Change in mechanism of MERTK activation in cell culture models using healthy and diseased monocytes in vitro and ex vivo | days 1 (Baseline), 3, 7, and 14; then followed 6-monthly for up to 36 months |
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Inclusion Criteria:
Exclusion Criteria:
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Prospective recruitment of patients with cirrhosis, acute decompensation, acute liver failure as pathological controls and healthy controls or controls with no liver disease at the Cantonal Hospital St. Gallen (KSSG), University Hospital Basel, St. Mary's Hospital, Imperial College London and King's College Hospital, London, UK.
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| Name | Affiliation | Role |
|---|---|---|
| Christine Bernsmeier, PD Dr. Dr. | Universitätsspital Basel, Departement Biomedizin, Gastroenterologie und Hepatologie | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University Hospital Basel, Hepatology Department and Laboratory | Basel | 4031 | Switzerland | |||
| Cantonal Hospital St. Gallen |
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Biological material will be stored in -80°C and -140°C freezers at the sites of recruitment.
If biological material (e.g. liver biopsies, liver resections, ascites, urine, gut biopsies) are sampled routinely for clinical reasons and exceeding material allows additional scientific investigations, a small amount of the material will be used. The samples will be destroyed 10 years after publication of the study
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| acute liver failure | sampling of biological material and health related data collection on days 1 (Baseline), 3, 7, and 14. If acutely decompensated patients re-compensate they will be followed 6-monthly for up to 36 months |
|
| healthy controls | sampling of biological material and health related data collection on day 1 (Baseline) |
|
| clinical data collection | Other | clinical data collection in order to document the stage of disease, the presence of infection and existing complications of cirrhosis (ascites, hepatic encephalopathy, renal dysfunction, pulmonary dysfunction) and concomitant disease. These data will be collected for clinical reasons as highly important in the context of patients with cirrhosis and possible decompensation or liver failure and will therefore not require additional time |
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| Health-related Questionnaires | Other | Health-related Questionnaires (Questionnaire_CLD) regarding sleep characteristics (Pittsburgh sleep Quality index, PSQI), daytime sleepiness (Epworth sleepiness scale, ESS), anxiety and depression (Hospital Anxiety and Depression Scale, HADS) and quality of life (EQ-5D-5L) |
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| Sampling other biological materials (e.g. liver biopsies, liver resections, ascites, urine, gut biopsies) | Other | Other biological material (e.g. liver biopsies, liver resections, ascites, urine, gut biopsies) will only be investigated if sampled for clinical reasons and if excessive material is available that is not needed for clinical purpose. |
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| Sankt Gallen |
| 9007 |
| Switzerland |
| King's College Hospital, Institute of Liver studies | London | SE5 9RS | United Kingdom |
| St. Mary's Hospital, Imperial College London, Section of Hepatology | London | W2 1PG | United Kingdom |
| ID | Term |
|---|---|
| D008107 | Liver Diseases |
| D005355 | Fibrosis |
| D065290 | Acute-On-Chronic Liver Failure |
| D017093 | Liver Failure |
| ID | Term |
|---|---|
| D004066 | Digestive System Diseases |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D017114 | Liver Failure, Acute |
| D048550 | Hepatic Insufficiency |
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| ID | Term |
|---|---|
| D001800 | Blood Specimen Collection |
| D006498 | Hepatectomy |
| D014554 | Urination |
| ID | Term |
|---|---|
| D013048 | Specimen Handling |
| D019411 | Clinical Laboratory Techniques |
| D019937 | Diagnostic Techniques and Procedures |
| D003933 | Diagnosis |
| D011677 | Punctures |
| D013514 | Surgical Procedures, Operative |
| D008919 | Investigative Techniques |
| D013505 | Digestive System Surgical Procedures |
| D014553 | Urinary Tract Physiological Phenomena |
| D012101 | Reproductive and Urinary Physiological Phenomena |
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