MERTK Signalling in Monocytes/Macrophages in Patients With Liver Disease
关键词
抽象
描述
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.
日期
| 最后验证: | 09/30/2019 |
| 首次提交: | 10/02/2019 |
| 提交的预估入学人数: | 10/02/2019 |
| 首次发布: | 10/03/2019 |
| 上次提交的更新: | 10/02/2019 |
| 最近更新发布: | 10/03/2019 |
| 实际学习开始日期: | 08/26/2015 |
| 预计主要完成日期: | 07/31/2020 |
| 预计完成日期: | 11/30/2020 |
状况或疾病
干预/治疗
Other: blood sampling for research purpose
Other: clinical data collection
Other: Health-related Questionnaires
Other: Sampling other biological materials (e.g. liver biopsies, liver resections, ascites, urine, gut biopsies)
相
手臂组
| 臂 | 干预/治疗 |
|---|---|
| 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 | |
| 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 | |
| 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) |
资格标准
| 有资格学习的年龄 | 18 Years 至 18 Years |
| 有资格学习的性别 | All |
| 取样方式 | Probability Sample |
| 接受健康志愿者 | 是 |
| 标准 | Inclusion Criteria: - Patients with compensated or decompensated chronic liver disease - Patients with acute- or acute-on-chronic chronic liver failure - Controls with no liver disease Exclusion Criteria: - Evidence of disseminated malignancy |
结果
主要结果指标
1. Change in MERTK signalling cascade on monocytes [days 1 (Baseline), 3, 7, and 14; then followed 6-monthly for up to 36 months]
2. Change in MERTK signalling cascade on tissue macrophages [days 1 (Baseline), 3, 7, and 14; then followed 6-monthly for up to 36 months]
次要成果指标
1. Change in mechanism of MERTK activation in cell culture models using monocytes [days 1 (Baseline), 3, 7, and 14; then followed 6-monthly for up to 36 months]
