S100A8/A9 and Innate Immunity in Liver Disease

NCT05793983 | Unknown

• 2 other identifiers: 2021.0073285573
• Study Type: observational
• Target: 100
• Locations: 1 country
• Sites: 1

Brief Summary

This observational study evaluates the concentration of immune protein S100A8/A9 in different liver failure syndromes, its interaction with the immune system and validity as an immunotherapeutic target to improve survival in patients with advanced cirrhosis and/or acute on chronic liver failure.

Conditions

Cirrhosis, Liver; Immune Suppression; Liver Failure, Acute on Chronic; Ascites Hepatic; Infections

Keywords

cirrhosis; acute-on-chronic liver failure; immune paralysis

Outcome Measures

Primary Outcomes (1)

• Concentration of plasma S100A8/A9

  The study will evaluate whether S100A8/A9 concentration can be used to predict clinical outcomes, such as mortality, the development of infection and/or organ failure. In the laboratory, it will evaluate the effect S100A8/A9 has on immune functional readouts including phagocytosis, oxidative burst and cytokine production, all of which are required for an effect immune response. Similarly, by blocking its action, the study will identify whether this is a potential immunotherapeutic strategy to improve the outcome of patients with high concentrations of the protein.

  1 years

Secondary Outcomes (2)

• Mortality

  1 years

• Development of infection

  1 years

Study Arms (11)

Patients with acute or chronic liver disease

1. Presence of chronic liver disease, or cirrhosis due to any aetiology (latter based upon a histopathological diagnosis or compatible laboratory data and radiological findings) 2. Acute alcoholic hepatitis 3. Acute liver failure due to any aetiology 4. Acute-on-chronic liver failure

Patients undergoing diagnostic or therapeutic abdominal paracentesis

Patients with acute or chronic liver disease of any aetiology undergoing clinically-indicated paracentesis for ascites

Patients undergoing broncho-alveolar lavage

1. Intubated patients with liver disease in intensive care 2. Undergoing a bronchoscopy or a non-directed broncho-alveolar lavage as part of their routine clinical care

Patients with acute or chronic liver disease undergoing liver biopsy

Patients with undergoing transjugular intrahepatic shunt (TIPSS) placement

Patients with acute or chronic liver disease undergoing orthoptic liver transplantation

Patients undergoing surgical liver resection or hepatectomy for liver-related diseases

Patients with ascites without chronic liver disease

1. Absence of cirrhosis based on clinical, radiological or histopathological features, including patients with non-cirrhotic portal hypertension, cardiac ascites (ascites due to heart failure) or patients with chronic kidney disease undergoing continuous ambulatory peritoneal dialysis (CAPD) 2. Presence of clinically significant ascites 3. Undergoing diagnostic or therapeutic paracentesis

Patients with sepsis without acute or chronic liver disease

Patients with haemochromatosis who undergo regular venesection

Healthy subjects

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Primary population is patients with acute or chronic liver disease admitted to hospital (including intensive care unit) or out-patient setting. Control subjects includes patients with sepsis, patients without liver disease but on continuous ambulatory peritoneal dialysis for renal replacement therapy (ascites control) and healthy subjects.

You may qualify if:

• A) Patients with acute or chronic liver disease:
• Presence of chronic liver disease, or cirrhosis due to any aetiology (latter based upon a histopathological diagnosis or compatible laboratory data and radiological findings)
• Acute alcoholic hepatitis (definition as per Crabb et al, 2016)35
• Acute liver failure due to any aetiology
• Acute-on-chronic liver failure (defined as per EASL-CLIF definition)17
• B) Patients undergoing diagnostic or therapeutic abdominal paracentesis Patients with acute or chronic liver disease of any aetiology undergoing clinically-indicated paracentesis for ascites
• C) Patients undergoing broncho-alveolar lavage
• Intubated patients with liver disease in intensive care
• Undergoing a bronchoscopy or a non-directed broncho-alveolar lavage as part of their routine clinical care
• D) Patients with acute or chronic liver disease undergoing liver biopsy (percutaneous or transjugular) as routine part of their clinical care
• E) Patients with portal hypertension (cirrhotic or non-cirrhotic) undergoing transjugular intrahepatic shunt (TIPSS) placement as part of their routine care
• F) Patients with acute or chronic liver disease undergoing orthoptic liver transplantation
• G) Patients undergoing surgical liver resection or hepatectomy for liver-related diseases
• Control groups:
• A) Patients with ascites without chronic liver disease:

Sponsors & Collaborators

• St George's, University of London: lead
• King's College Hospital NHS Trust: collaborator

Study Sites (1)

Arjuna Singanayagam

Wandsworth, London, SW17 0RE, United Kingdom

RECRUITING

Biospecimen

Retention: SAMPLES WITH DNA

Whole blood including derives peripheral blood mononuclear cells, plasma and serum Ascites and ascitic cells Faecal material Urine Broncho-alveolar lavage fluid Liver tissue

MeSH Terms

Conditions

Liver Cirrhosis; Acute-On-Chronic Liver Failure; Infections; Fibrosis

Condition Hierarchy (Ancestors)

Liver Diseases; Digestive System Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Liver Failure, Acute; Liver Failure; Hepatic Insufficiency

Study Officials

• Arjuna Singanayagam, MBBS; PhD

  St George's, University of London

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Arjuna Singanayagam, MBBS; PhD

CONTACT

02086729944; asingana@sgul.ac.uk

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 8, 2021
• First Posted: March 31, 2023
• Study Start: September 28, 2021
• Primary Completion: September 1, 2023
• Study Completion: September 1, 2024
• Last Updated: March 31, 2023

Record last verified: 2023-03

Data Sharing

• IPD Sharing: Will not share

Locations

GB (1)