MERTK Signalling in Monocytes/Macrophages in Patients With Liver Disease

Completed

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

• Registration Number: NCT04116242
• Lead Sponsor: University Hospital, Basel, Switzerland

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.

Study Timeline

• Study Start: 2015-08-27
• Study First Submitted: 2019-10-03
• Study First Submitted QC: 2019-10-03
• Study First Posted: 2019-10-04
• Status Verified: 2024-06
• Primary Completion: 2024-06-10
• Study Completion: 2024-06-10
• Last Update Submitted: 2024-06-24
• Last Update Posted: 2024-06-25

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 277

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

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Exclusion Criteria

• Evidence of disseminated malignancy

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Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
cirrhosis of the liver, stadium Child B	Health-related Questionnaires	sampling of biological material and health related data collection longitudinally in 6-monthly intervals up to 36 months
healthy controls	blood sampling for research purpose	sampling of biological material and health related data collection on day 1 (Baseline)
healthy controls	Health-related Questionnaires	sampling of biological material and health related data collection on day 1 (Baseline)
healthy controls	clinical data collection	sampling of biological material and health related data collection on day 1 (Baseline)
cirrhosis of the liver, stadium Child A	blood sampling for research purpose	sampling of biological material and health related data collection longitudinally in 6-monthly intervals up to 36 months
cirrhosis of the liver, stadium Child A	clinical data collection	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 other biological materials (e.g. liver biopsies, liver resections, ascites, urine, gut biopsies)	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	clinical data collection	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
cirrhosis of the liver, stadium Child A	Health-related Questionnaires	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	clinical data collection	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	blood sampling for research purpose	sampling of biological material and health related data collection longitudinally in 6-monthly intervals up to 36 months
cirrhosis of the liver, acutely decompensated	Health-related Questionnaires	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	blood sampling for research purpose	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 other biological materials (e.g. liver biopsies, liver resections, ascites, urine, gut biopsies)	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
cirrhosis of the liver, stadium Child A	Sampling other biological materials (e.g. liver biopsies, liver resections, ascites, urine, gut biopsies)	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	blood sampling for research purpose	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	clinical data collection	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 other biological materials (e.g. liver biopsies, liver resections, ascites, urine, gut biopsies)	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	Health-related Questionnaires	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 other biological materials (e.g. liver biopsies, liver resections, ascites, urine, gut biopsies)	sampling of biological material and health related data collection longitudinally in 6-monthly intervals up to 36 months
cirrhosis of the liver, acutely decompensated	blood sampling for research purpose	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
cirrhosis of the liver, acutely decompensated	clinical data collection	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	Health-related Questionnaires	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

Primary Outcome Measures

Name	Time	Method
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
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

Secondary Outcome Measures

Name	Time	Method
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

Trial Locations

Locations (4)

University Hospital Basel, Hepatology Department and Laboratory; 🇨🇭 Basel, Switzerland

Cantonal Hospital St. Gallen; 🇨🇭 St. Gallen, Switzerland

King's College Hospital, Institute of Liver studies; 🇬🇧 London, United Kingdom

St. Mary's Hospital, Imperial College London, Section of Hepatology; 🇬🇧 London, United Kingdom