MERTK Signalling in Monocytes/Macrophages in Patients With Liver Disease

University Hospital Basel

Status: Completed

Conditions: Acute-On-Chronic Liver Failure; Liver Failure; Cirrhosis of the Liver; Liver Disease

Treatments: Other: Sampling other biological materials (e.g. liver biopsies, liver resections, ascites, urine, gut biopsies); Other: Health-related Questionnaires; Other: blood sampling for research purpose; Other: clinical data collection

Study type: Observational

Funder types: Other

Identifiers

NCT04116242

EKSG 15/074 me19Bernsmeier2;

Details and patient eligibility

About

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.

Full 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.

Enrollment: 277 patients

Sex: All

Ages: 18+ years old

Volunteers: Accepts Healthy Volunteers

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

Trial design

277 participants in 6 patient groups

cirrhosis of the liver, stadium Child A

Description:

sampling of biological material and health related data collection longitudinally in 6-monthly intervals up to 36 months

Treatment:

Other: clinical data collection

Other: blood sampling for research purpose

Other: Health-related Questionnaires

Other: Sampling other biological materials (e.g. liver biopsies, liver resections, ascites, urine, gut biopsies)

cirrhosis of the liver, stadium Child B

Description:

sampling of biological material and health related data collection longitudinally in 6-monthly intervals up to 36 months

Treatment:

Other: clinical data collection

Other: blood sampling for research purpose

Other: Health-related Questionnaires

Other: Sampling other biological materials (e.g. liver biopsies, liver resections, ascites, urine, gut biopsies)

cirrhosis of the liver, stadium Child C

Description:

sampling of biological material and health related data collection longitudinally in 6-monthly intervals up to 36 months

Treatment:

Other: clinical data collection

Other: blood sampling for research purpose

Other: Health-related Questionnaires

Other: Sampling other biological materials (e.g. liver biopsies, liver resections, ascites, urine, gut biopsies)

cirrhosis of the liver, acutely decompensated

Description:

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

Treatment:

Other: clinical data collection

Other: blood sampling for research purpose

Other: Health-related Questionnaires

Other: Sampling other biological materials (e.g. liver biopsies, liver resections, ascites, urine, gut biopsies)

acute liver failure

Description:

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

Treatment:

Other: clinical data collection

Other: blood sampling for research purpose

Other: Health-related Questionnaires

Other: Sampling other biological materials (e.g. liver biopsies, liver resections, ascites, urine, gut biopsies)

healthy controls

Description:

sampling of biological material and health related data collection on day 1 (Baseline)

Treatment:

Other: clinical data collection

Other: blood sampling for research purpose

Other: Health-related Questionnaires