NCT04116242

MERTK Signalling in Monocytes/Macrophages in Patients With Liver Disease

• Status: Completed
• Phase: —
• Study type: Observational
• Enrollment: 277 (actual)
• Sponsor: University Hospital, Basel, Switzerland · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Accepted

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.

Conditions

• Liver Disease
• Cirrhosis of the Liver
• Acute-On-Chronic Liver Failure
• Liver Failure

Interventions

Type	Name	Description
OTHER	blood sampling for research purpose	blood sampling for research purpose (about 30ml) taken by venepuncture or from intravenous catheters if already in place
OTHER	clinical data collection	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
OTHER	Health-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)
OTHER	Sampling 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.

Timeline

• Start date: 2015-08-27
• Primary completion: 2024-06-10
• Completion: 2024-06-10
• First posted: 2019-10-04
• Last updated: 2024-06-25

Locations

4 sites across 2 countries: Switzerland, United Kingdom