Liver / Hepatocyte

This study machine-perfuses livers that are unsuitable for transplantation using blood at normal body temperature.

It focuses on DCD (donation after circulatory death) livers, which are typically associated with a long period without blood circulation before they are transplanted.

This study can transplant the livers it receives.

• Full Title: Development of pre-transplant normothermic perfusion reconditioning for human livers donated after circulatory death
• Start Date: 1st August 2014
• Sponsor Organisation: University of Cambridge
• ODT Study Number: 21

This study removes the cells from the livers it receives in a process called decellularisation. What’s left is a 3D scaffold, which can be populated with new liver cells.

The long-term goal is that a person with end-stage liver disease could have a replacement liver created for them, using their own cells, so that there’s no need to take immunosuppressant medication after transplant.

• Full title: Organ regeneration and disease modelling using 3D biological scaffold
• Start date: 3^rd March 2014
• Sponsor organisation: University College London (UCL)
• ODT study number: 50

One potential strategy to improve the quality of livers that are donated for transplantation is to perfuse them on a machine outside of the body, with cold preservation solution or warm blood, both with added oxygen.

This study tests out these techniques to check that they are safe and that they improve the liver’s quality, with the hope of being able to transplant these.

• Full title: Establishing ex-vivo normothermic and hypothermic perfusion of livers for transplantation
• Start date: 6^th October 2015
• Sponsor organisation: Newcastle University
• ODT study number: 52
• Study Website: Blood and Transplant Research Unit in ODT

Livers that go to this study are perfused on a machine at body temperature to assess their function. Cells called hepatic progenitors are isolated and cultured to increase their numbers.

This study then assesses whether these cells can stimulate repair in a damaged liver model.

• Full title: Human Hepatic Progenitor Cells as a Source of Liver Regeneration
• Start date: 27^th July 2015
• Sponsor organisation: University of Edinburgh
• ODT study number: 56

This study uses a perfusion machine, which circulates blood at normal body temperature through the research liver. Whilst on the machine, the liver can be assessed and be given treatments to improve its function.

This study will optimise the conditions of the perfusion machine so that livers can stay on it for longer. It will also assess whether the immune cells in the liver can be activated to repair disease.

• Full title: Normothermic Liver Perfusion Study (The development of NMLP for improvement of marginal human donor liver quality)
• Start date: 1^st January 2014
• Sponsor organisation: University of Birmingham
• ODT study number: 35

When the liver is mildly or moderately injured or diseased, it can repair itself using ‘stem cells’. These cells are also known as hepatic progenitor cells. This study separates these cells from the liver and transplants them into mice who have major liver disease. If the cells start to repair the mice livers, then there is the potential to use these cells to treat humans with liver failure.

This would be the start of developing a transplant programme where only an injection of cells is given rather than the whole liver being replaced.

• Full title: Hepatocyte Transplantation Project: Studies on isolated hepatocytes
• Start date: 20^th March 2017
• Sponsor organisation: King’s College London
• ODT study number: 68
• Study website

The symptoms of end-stage liver disease (no matter what the initial cause) are linked by liver inflammation. Understanding this inflammation, how it’s triggered and what the consequences will help to prevent end-stage liver disease and the need for a liver transplant.

• Full title: Investigating how inflammation determines the development and outcome of inflammatory liver diseases, and whether new targets for drug therapies can be identified
• Start date: 8^th May 2019
• Sponsor organisation: University of Birmingham
• ODT study number: 84

A third of donated livers cannot be used for transplants due to the presence of fat within the liver cells (known as non-alcoholic fatty liver disease, NAFLD).

Transplanting a fatty liver carries a greater risk to the patient compared to a normal liver as these livers do not tolerate conventional ice-box storage before transplantation.

Our preliminary experiments point to an innovative defatting strategy for treatment of fatty human livers that were declined for transplantation. These livers were preserved on a machine in very similar conditions to those in the body (termed normothermic preservation).

We added a combination of currently available drugs to release fat from liver cells, and we then removed the fat using a filter. This reduced the amount of fat in the liver and improved its function.

However, evidence suggests that other key pathways may further enhance the success of these defatting strategies, in particular, pathways associated with oxygen sensing that are regulated by hypoxia inducible factors (HIFs). HIFs are activated in low oxygen environments and have both a protective and deleterious effect in the progression of NAFLD.

Evidence from pre-clinical experiments suggests that HIF expression can be selectively modulated using pharmacological agents thereby providing therapeutic targets for NAFLD.

We will initially investigate the effect of the defatting strategies on HIF expression within the liver using samples from our preliminary study. This will inform the basis our main study where we anticipate that the selective pharmacological modulation of HIF pathway during normothermic liver preservation will improve functional outcomes.    

• Full title: High-risk steatotic donor livers in the era of normothermic machine perfusion: Application of novel therapies to achieve transplantability criteria
• Start date: 28th July 2020
• Sponsor organisation: University of Oxford
• ODT study number: 102

During chronic liver injury, scarring or fibrosis gradually accumulates and replaces functional liver tissue.

The liver becomes hard and nodular (also termed ‘cirrhotic’), causing alterations in normal blood flow to the liver and other organs.

Loss of functional liver mass also results in significant compromise in key hepatic functions such as protein synthesis, detoxification ability and nutrient handling.

All of these can lead to eventual liver failure, damage to other organs and either death or requirement for transplantation.

There is currently no approved medicinal therapy to treat liver fibrosis and every year over 4000 patients in the UK die from liver cirrhosis as a result of end stage disease and fibrosis.

The study team wishes to gain as much information as possible from the samples they receive to ensure that they can design tools to diagnose, stage and treat not only liver and gut fibrosis, but also possibly fibrosis in other organs that may arise through shared molecular mechanisms.

• Full title: Understanding the mechanisms that drive development and resolution of liver and bowel fibrosis. Identification of new drug targets.
• Start date: 7th September 2020
• Sponsor organisation: University of Birmingham
• ODT study number: 86