Transcriptional Analysis of Mechanisms in Liver Failure and Sepsis

NCT07131969 | Not Yet Recruiting

• 1 other identifier: A097365
• Study Type: observational
• Target: 100
• Locations: 1 country
• Sites: 7

Brief Summary

Context Acute liver failure (ALF) is a life-threatening condition that occurs on the background of a healthy liver. The most common cause of acute liver failure in the UK is paracetamol overdose. Acute liver failure results from liver damage and activation of the body's inflammatory defences with subsequent damage to other organs including kidneys, lungs and heart. This often requires life support in an intensive care unit before liver transplantation (LT), the only currently available and effective rescue treatment for acute liver failure. Challenge Patient factors and organ availability limit who can benefit from liver transplant. At present there are no effective alternative therapies for patients who do not get a liver transplant, and survival rates in these situations are poor. The underlying mechanisms of inflammation are poorly understood, thus therapies are limited. Aim The investigators research aims to understand the mechanisms that underpin the inflammation seen in acute liver failure by studying the inflammatory cells in the blood and examining their cellular programmes. This will allow the investigators to identify pathways that are activated and understand how the liver and blood interact to spread inflammation around the body. The investigators aim to identify targets for disease-modifying therapies to avert the need for liver transplant. Importance Understanding how the body responds to acute liver failure, and whether there are different patterns of inflammatory response, will enable trials of immune-modulating drugs to prevent the need for liver transplantation or prolong the time a patient can wait for an organ. This has the potential to help improve organ availability for other patients and save lives in acute liver failure.

Conditions

Acute Liver Failure; Sepsis

Keywords

acute liver failure; sepsis; transcriptional analysis; predictors; paracetamol overdose; acetaminophen overdose

Outcome Measures

Primary Outcomes (1)

• Mortality

  From enrolment until at least 1-year

Secondary Outcomes (3)

• Transplant free survival

  From enrolment to at least one year

• Length of stay - ICU and hospital

  From enrolment

• Transplant free mortality

  From enrolment until death (at least until 1year)

Study Arms (1)

Patients with acute liver failure or sepsis

Other: blood draw

Interventions

blood draw OTHER

Venous blood sampling into Tempus tube for RNA-sequencing

Patients with acute liver failure or sepsis

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Patients with acute liver failure due to acetaminophen overdose OR sepsis who are admitted to ICU

You may qualify if:

• acute liver failure due to acetaminophen (paracetamol) overdose admitted to ICU
• all cause sepsis admitted to ICU

You may not qualify if:

• age \<16y

Sponsors & Collaborators

• University of Cambridge: lead
• European Society of Intensive Care Medicine: collaborator

Study Sites (7)

University Hospitals Birmingham

Birmingham, United Kingdom

Location

Addenbrooke's Hospital

Cambridge, United Kingdom

Location

Royal Infirmary of Edinburgh

Edinburgh, United Kingdom

Location

Leeds General Infirmary

Leeds, United Kingdom

Location

Kings College Hospital

London, United Kingdom

Location

Royal Free Hospital

London, United Kingdom

Location

Freeman Hospital

Newcastle, United Kingdom

Location

Biospecimen

Retention: SAMPLES WITHOUT DNA

Whole blood collected in Tempus tubes for RNA-sequencing

MeSH Terms

Conditions

Liver Failure, Acute; Sepsis

Interventions

Blood Specimen Collection

Condition Hierarchy (Ancestors)

Liver Failure; Hepatic Insufficiency; Liver Diseases; Digestive System Diseases; Infections; Systemic Inflammatory Response Syndrome; Inflammation; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Specimen Handling; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Punctures; Surgical Procedures, Operative; Investigative Techniques

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal investigator

Study Record Dates

• First Submitted: August 12, 2025
• First Posted: August 20, 2025
• Study Start: September 1, 2025
• Primary Completion (Estimated): September 1, 2027
• Study Completion (Estimated): September 1, 2028
• Last Updated: August 26, 2025

Record last verified: 2025-08

Locations

GB (7)