Tissue Models for Liver Disease

NCT05255042 | Completed

• 1 other identifier: 0814
• Study Type: observational
• Target: 36
• Locations: 1 country
• Sites: 1

Brief Summary

The human immune response to bacterial and viral local and systemic infection are fairly well understood, but we lack details on the earliest phases. Better knowledge of these events would be important for the prevention and treatment of severe bacterial or viral disease. From models of infection, we have data showing that bacteria replicate in a specific type of cells in the liver from where the bacteria then seed to the blood to cause blood stream infection. In order to gain more relevant data for humans, we have developed a spleen and liver perfusion model using pig organs. This model confirms our previous work and most importantly will now allow us to study these events in human organs. Primary Objectives: The primary objective of the study is to identify therapies acting on the initial events during invasive bacterial and viral infection. Secondary Objectives: The secondary objective of this study is to provide novel in vitro and ex vivo models of human liver macrophages to study the impact of therapies for invasive infection. The Primary Endpoint of the study is to increase the resistance of liver macrophages to infection at least tenfold after treatment. The Primary Outcome Measure of the study is the reduction of bacterial or viral load at pre-determined time-points.

Conditions

Liver Diseases

Outcome Measures

Primary Outcomes (1)

• Reduction of the load and replication of infectious agents by host directed interventions

  Reduction of the number of infectious agents per gram of tissue by therapies acting on the initial events during invasive infection.

  3.5 Years

Secondary Outcomes (1)

• Protocol for seven-day survival of tissue slices and primary macrophage cell cultures

  3.5 Years

Study Arms (1)

Trial Participants

Overall Description of Trial Participants: The liver organ samples included in this project will be from patients undergoing elective surgery for a lesion in the liver in the HPB Unit of the Leicester General Hospital. No change in the surgical procedure or recruiting results from this study and the use of the samples. Inclusion Criteria: The samples included in this project will be from patients undergoing elective liver surgery in the HPB Unit of the Leicester General Hospital. The criteria for inclusion of liver segment samples from radical surgery are adult age and presence of hepatic tissue in the discarded material after hepato-pancreato-biliary surgery. Exclusion Criteria: The main exclusion criterion is acute invasive infection, but these patients are automatically excluded from major surgery. Vulnerable groups will not be recruited.

Other: organ and tissue sample collection only

Interventions

organ and tissue sample collection only OTHER

Collection of liver segments removed by radical surgery of hepatic lobes, but not submitted to pathology

Trial Participants

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

The liver segment samples included in this project will be from patients undergoing elective surgery for a lesion in the liver in the HPB Unit of the Leicester General Hospital. No change in the surgical procedure or recruiting results from this study and the use of the samples.

You may qualify if:

• The samples included in this project will be from patients undergoing elective surgery in the HPB Unit of the Leicester General Hospital.
• Liver segment samples from radical surgery are adult age (18-80 years)
• Presence of liver segment tissue in the discarded material after hepatopancreato-biliary surgery.

You may not qualify if:

• Samples from patients treated with antibiotics prior to explant or surgery will not be excluded, but samples will have to be tested for residual antibiotic activity.

Sponsors & Collaborators

• University of Leicester: lead
• University Hospitals, Leicester: collaborator

Study Sites (1)

UHL NHS Trust - Leicester General Hospital

Leicester, LE5 4PW, United Kingdom

Location

Related Publications (2)

• Wanford JJ, Hames RG, Carreno D, Jasiunaite Z, Chung WY, Arena F, Di Pilato V, Straatman K, West K, Farzand R, Pizza M, Martinez-Pomares L, Andrew PW, Moxon ER, Dennison AR, Rossolini GM, Oggioni MR. Interaction of Klebsiella pneumoniae with tissue macrophages in a mouse infection model and ex-vivo pig organ perfusions: an exploratory investigation. Lancet Microbe. 2021 Dec;2(12):e695-e703. doi: 10.1016/S2666-5247(21)00195-6.

  PMID: 34901898 BACKGROUND

• Carreno D, Wanford JJ, Jasiunaite Z, Hames RG, Chung WY, Dennison AR, Straatman K, Martinez-Pomares L, Pareek M, Orihuela CJ, Restrepo MI, Lim WS, Andrew PW, Moxon ER, Oggioni MR. Splenic macrophages as the source of bacteraemia during pneumococcal pneumonia. EBioMedicine. 2021 Oct;72:103601. doi: 10.1016/j.ebiom.2021.103601. Epub 2021 Oct 4.

  PMID: 34619637 BACKGROUND

Biospecimen

Retention: SAMPLES WITH DNA

Experiments include ex vivo liver segment perfusion and infection with bacteria. The trial aimed at recruitment of 96 participants. During the trial 36 patients were randomised and 20 liver segments perfused. Biopsies of the perfused liver segments are processed for in vitro tissue culture or stored frozen for immunomicroscopy.

MeSH Terms

Conditions

Liver Diseases

Condition Hierarchy (Ancestors)

Digestive System Diseases

Study Officials

• Marco R Oggioni, MD

  University of Leicester

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: January 6, 2022
• First Posted: February 24, 2022
• Study Start: September 8, 2021
• Primary Completion: June 25, 2025
• Study Completion: June 25, 2025
• Last Updated: May 11, 2026

Record last verified: 2023-10

Data Sharing

• IPD Sharing: Will not share

Locations

GB (1)