Liver Disease, Cirrhosis of the Liver, Acute-On-Chronic Liver Failure, Liver Failure
Conditions
Keywords
immunoparesis, monocyte dysfunction, MER receptor tyrosine kinase (MERTK), innate immune dysfunction, circulating monocytes/macrophages, MERTK signalling
Brief summary
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.
Detailed description
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.
Interventions
OTHERblood sampling for research purpose
blood sampling for research purpose (about 30ml) taken by venepuncture or from intravenous catheters if already in place
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
OTHERHealth-related Questionnaires
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)
OTHERSampling other biological materials (e.g. liver biopsies, liver resections, ascites, urine, gut biopsies)
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.
Sponsors
Swiss National Science Foundation
University Hospital, Basel, Switzerland
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
Yes
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in MERTK signalling cascade on monocytes | days 1 (Baseline), 3, 7, and 14; then followed 6-monthly for up to 36 months | 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 |
| Change in MERTK signalling cascade on tissue macrophages | days 1 (Baseline), 3, 7, and 14; then followed 6-monthly for up to 36 months | 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 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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 | Change in mechanism of MERTK activation in cell culture models using healthy and diseased monocytes in vitro and ex vivo |
Countries
Switzerland, United Kingdom
Outcome results
None listed