S100A8/A9 and Innate Immunity in Liver Disease

NCT ID: NCT05793983

Last Updated: 2023-03-31

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Total Enrollment

100 participants

Study Classification

OBSERVATIONAL

Study Start Date

2021-09-28

Study Completion Date

2024-09-01

Brief Summary

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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.

Detailed Description

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A paradox exists in chronic liver disease whereby there is a general recognition that chronic inflammation is part of the pathophysiology, heightened when there is an acute deterioration and organ failure (acute-on-chronic liver failure), yet there is an increased susceptibility to infection due to a dysfunctional immune system, which is often the trigger for organ failure and the reason for death in these patients.

A danger signal reported in other inflammatory conditions called S100A8/A9 (calprotectin) is known to activate the immune system by production of pro-inflammatory cytokines but has also been observed to promote the development immunosuppressive signals (e.g. IL-10 and MDSCs).

In an attempt to explain this paradox in liver disease, this study proposes to identify at the cellular and molecular level, the triggers for S100A8/A9 production, how it varies with time in stable patients and those that have acute deteriorations including the development of organ failure, and its interaction with innate immune cells in the circulation and at tissue level.

By studying this, the Investigators hope to be able to identify immunotherapeutic targets and understand whether potential immunotherapy could be applied locally or systemically. The Investigators' observations in this study could provide the basis for the future development of clinical immunomodulating agents, which may ameliorate immunopathology, reduce susceptibility to infection and could reduce mortality in critically ill patients with liver disease. Findings in this study may also have more generalizable impact especially with the recent recognition in the COVID-19 pandemic that immunomodulatory therapies may improve the clinical outcomes of inflammatory phenotypes in virus-induced severe sepsis.

Conditions

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

Keywords

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cirrhosis acute-on-chronic liver failure immune paralysis

Study Design

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Observational Model Type

COHORT

Study Time Perspective

PROSPECTIVE

Study Groups

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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

No interventions assigned to this group

Patients undergoing diagnostic or therapeutic abdominal paracentesis

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

No interventions assigned to this group

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

No interventions assigned to this group

Patients with acute or chronic liver disease undergoing liver biopsy

No interventions assigned to this group

Patients with undergoing transjugular intrahepatic shunt (TIPSS) placement

No interventions assigned to this group

Patients with acute or chronic liver disease undergoing orthoptic liver transplantation

No interventions assigned to this group

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

No interventions assigned to this group

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

No interventions assigned to this group

Patients with sepsis without acute or chronic liver disease

No interventions assigned to this group

Patients with haemochromatosis who undergo regular venesection

No interventions assigned to this group

Healthy subjects

No interventions assigned to this group

Eligibility Criteria

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Inclusion Criteria

A) 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 (definition as per Crabb et al, 2016)35
3. Acute liver failure due to any aetiology
4. 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

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

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:

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

B) Patients with sepsis without acute or chronic liver disease

C) Patients with haemochromatosis without liver disease or end-organ damage who undergo regular venesection

D) Healthy subjects
Minimum Eligible Age

18 Years

Maximum Eligible Age

80 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

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King's College Hospital NHS Trust

OTHER

Sponsor Role collaborator

St George's, University of London

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Arjuna Singanayagam, MBBS; PhD

Role: PRINCIPAL_INVESTIGATOR

St George's, University of London

Locations

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Arjuna Singanayagam

Wandsworth, London, United Kingdom

Site Status RECRUITING

Countries

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United Kingdom

Central Contacts

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Arjuna Singanayagam, MBBS; PhD

Role: CONTACT

Phone: 02086729944

Email: [email protected]

Facility Contacts

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Arjuna Singanayagam, MBBS; PhD

Role: primary

Other Identifiers

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285573

Identifier Type: OTHER

Identifier Source: secondary_id

2021.0073

Identifier Type: -

Identifier Source: org_study_id