Clinical trial NCT04116242: MERTK Signalling in Monocytes/Macrophages in Patients With Liver Disease
Official title: MERTK Signalling in Monocytes/Macrophages in Patients With Liver Disease
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Liver Disease
Cirrhosis of the Liver
Acute-On-Chronic Liver Failure
Liver Failure
Keywords: immunoparesis
monocyte dysfunction
MER receptor tyrosine kinase (MERTK)
innate immune dysfunction
circulating monocytes/macrophages
MERTK signalling
Lead sponsor: University Hospital, Basel, Switzerland
Sponsor class: OTHER
Collaborators: name: Swiss National Science Foundation
First posted: 2019-10-04
Enrollment: 277
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: Prospective recruitment of patients with cirrhosis, acute decompensation, acute liver failure as pathological controls and healthy controls or controls with no liver disease at the Cantonal Hospital St. Gallen (KSSG), University Hospital Basel, St. Mary's Hospital, Imperial College London and King's College Hospital, London, UK.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Change in MERTK signalling cascade on monocytes
timeFrame: days 1 (Baseline), 3, 7, and 14; then followed 6-monthly for up to 36 months
measure: Change in MERTK signalling cascade on tissue macrophages
timeFrame: days 1 (Baseline), 3, 7, and 14; then followed 6-monthly for up to 36 months
Secondary outcomes:
measure: Change in mechanism of MERTK activation in cell culture models using monocytes
timeFrame: days 1 (Baseline), 3, 7, and 14; then followed 6-monthly for up to 36 months
Other outcomes:
Locations:
city: Basel
country: Switzerland
facility: University Hospital Basel, Hepatology Department and Laboratory
city: St. Gallen
country: Switzerland
facility: Cantonal Hospital St. Gallen
city: London
country: United Kingdom
facility: King's College Hospital, Institute of Liver studies
city: London
country: United Kingdom
facility: St. Mary's Hospital, Imperial College London, Section of Hepatology
Study officials:
affiliation: Universitätsspital Basel, Departement Biomedizin, Gastroenterologie und Hepatologie
name: Christine Bernsmeier, PD Dr. Dr.
role: PRINCIPAL_INVESTIGATOR
References: