Biomarkers in Liver Failure

Identification of Outcome Biomarkers in Patients With Liver Failure.

Acute liver injury (ALI) and acute liver failure (ALF) are rare clinical conditions, the latter often associated with a poor outcome. To improve outcomes for these patients, clinicians need to develop a clearer understanding of the pathophysiology of this condition. Biomarkers and novel imaging techniques are vital to investigating and understanding the pathophysiology of ALI. Patients with ALI or ALF aged over 16 and due to any cause will be eligible to take part in the study. The study will involve collection of biological samples (blood, urine, stool and breath) from included patients once daily for up to 7 days. For patients undergoing liver transplantation, a small sample of explanted (removed) liver tissue will be obtained. A small subgroup of patients with paracetamol induced acute liver failure will be eligible to be included in a pilot MRI (magnetic resonance imaging) study, which will involve two MRI scans during the first 7 days of their admission. All patients will be recruited from the Royal Infirmary of Edinburgh.

Study Overview

• Status: Not yet recruiting
• Conditions: Acute on Chronic Hepatic Failure; Acute Liver Failure; Acute Liver Injury
• Intervention / Treatment: Radiation: Non-contrast magnetic resonance imaging; Other: Biological sampling

Detailed Description

For inpatients, the investigators wish to collect biological samples from each patient once daily for the first seven days of their admission. 25mls of blood will be taken daily for research purposes, at the same time at routine clinical samples to reduce discomfort from additional venepuncture. One urine sample will be taken daily (which can be taken from a catheter if the patient has a catheter in place), and a sample of stool if the patient moves their bowels. The investigators wish to collect breath for analysis, at one point during the first seven days of admission. Breath analysis requires the patients to be fasted for four hours (with the exception of water) prior to the test. If the patient undergoes liver transplantation during their admission, a small sample of explanted liver tissue will be obtained for later analysis.

For outpatients (acute liver injury, stable cirrhotics, non-cirrhotic liver disease), the investigators will ask them to attend the ward or the outpatient department for collection of biological samples. The investigators will take 25 mls of blood as above, along with a urine and stool sample if they are able to provide this at their first attendance. Breath analysis will also be undertaken during this visit to the hospital, after a 4 hour fast (with the exception of water). Outpatients will then be asked to return one month later, when further blood (25mls), urine and stool samples will be collected.

As a pilot study, the investigators wish to perform MRI scanning on a subset of 10 patients with paracetamol induced acute liver failure. Paracetamol induced acute liver failure is associated with a particularly rapid course, characterised by hepatic encephalopathy and renal impairment. In view of the potential for renal impairment, intravenous contrast will not be used for these scans, but alternative techniques employed such as artertial spin labelling.

The participant does not need to consent to each individual part of the study to be able to take part.

• Study Type: Observational
• Enrollment (Anticipated): 200

Contacts and Locations

• Study Contact: Name: Kenneth Simpson, MD, PhD; Phone Number: 0044 131 242 1621; Email: k.simpson@ed.ac.uk

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 80 years (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

1. Acute liver failure
2. Acute liver injury
3. Acute on chronic hepatic failure
4. Stable cirrhotics
5. Non-cirrhotic liver disease

Description

Inclusion Criteria:

• acute liver injury (newly deranged liver function tests (LFTs) and coagulopathy with International Normalized Ratio (INR) >1.5 in absence of chronic liver disease)
• acute liver failure ( as above, plus hepatic encephalopathy)
• acute on chronic liver failure (worsening of LFTS and development of at least 1 organ failure in patient with cirrhosis)
• stable cirrhosis
• non-cirrhotic liver disease

Exclusion Criteria:

• refusal of consent
• withdrawal of consent

Study Plan

How is the study designed?

Number of groups / cohorts

5

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Acute Liver Failure; biological sampling; MRI scanning for patients with paracetamol induced acute liver failure	Radiation: Non-contrast magnetic resonance imaging; Other: Biological sampling; Blood, urine, stool and breath sampling and analysis
Acute Liver Injury; - biological sampling	Other: Biological sampling; Blood, urine, stool and breath sampling and analysis
Acute on Chronic Hepatic Injury; - biological sampling	Other: Biological sampling; Blood, urine, stool and breath sampling and analysis
Stable Cirrhotics; - biological sampling	Other: Biological sampling; Blood, urine, stool and breath sampling and analysis
Non-cirrhotic liver disease; - biological sampling	Other: Biological sampling; Blood, urine, stool and breath sampling and analysis

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Identification of biomarkers and radiological markers predictive of development of complications and outcomes in acute liver injury and acute liver failure.	10 years

Secondary Outcome Measures

Outcome Measure	Time Frame
Identification of proteins involved in the pathogenesis of acute liver injury and acute liver failure	10 years

Collaborators and Investigators

• Sponsor: University of Edinburgh
• Collaborators: NHS Lothian

Study record dates

Study Major Dates

• Study Start: October 1, 2016
• Primary Completion (Anticipated): October 1, 2026
• Study Completion (Anticipated): November 1, 2026

Study Registration Dates

• First Submitted: July 11, 2016
• First Submitted That Met QC Criteria: July 11, 2016
• First Posted (Estimate): July 14, 2016

Study Record Updates

• Last Update Posted (Estimate): August 30, 2016
• Last Update Submitted That Met QC Criteria: August 29, 2016
• Last Verified: July 1, 2016

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Liver Diseases; Liver Failure; Hepatic Insufficiency; Liver Failure, Acute
• Other Study ID Numbers: AC16086

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED