There are many challenges associated with the success of liver transplantation procedures, including the potential for organ injuries.
In two ground-breaking studies, researchers have shed light on innovative approaches to enhance liver transplant success and address issues surrounding organ shortages.
The first study, conducted by researchers at UCLA, delves into the role of the CEACAM1 protein in safeguarding the liver during transplantation.
CEACAM1, a protein previously not well understood in the context of transplantation, has emerged as a critical player in protecting the liver from harm during transplantation.
The researchers focused on addressing ischaemic reperfusion injury, a common issue when restoring blood supply during transplantation, and found that CEACAM1’s protective potential is vital.
Lead author Kenneth Dery and his team underscored that the events surrounding transplantation could activate the recipient’s immune response, negatively impacting transplant outcomes.
Understanding and addressing factors contributing to organ shortages is crucial for expanding the donor pool.
The study highlighted a specific version of CEACAM1, labelled CEACAM1-S, which significantly limits cellular injury and enhances mouse liver function.
It also found a connection between CEACAM1-S and a regulator of oxygen consumption called Hypoxia Inducible Factor 1 (HIF-1a).
This association predicts improved outcomes in human transplantation and immune functioning.
The researchers further revealed a novel gene expression pathway, alternative splicing, which becomes active in response to oxygen stress and ischaemia.
This pathway allows cells to diversify their protein production during times of danger, inflammation and injury.
The study’s findings are particularly promising for potential therapeutic applications. By stabilising HIF-1a under normal oxygen conditions, researchers effectively increased the protective version of CEACAM1-S.
This intervention demonstrates a proof-of-concept that could lead to future therapeutic strategies.
The co-authors from various institutions, including UCLA, UT Health, Kyoto University, and the University of South Carolina, have highlighted the potential of CEACAM1-S as a marker of liver quality, offering therapeutic benefits for transplantation and acute liver injury cases.
The second study, led by a liver transplant team at London’s Royal Free Hospital (RFH) and the University of Oxford, addresses another critical issue in liver transplantation – the suitability of fatty livers for successful transplantation.
Approximately one-third of donated livers are discarded due to non-alcoholic fatty liver disease (NAFLD).
Fatty livers are often deemed unsuitable for transplantation due to their susceptibility to damage during storage and transport in cold conditions.
Professor Peter Friend and his team at the University of Oxford are pioneering the DeFat study, which explores the feasibility of a ‘defatting’ strategy to improve the viability of fatty livers for transplantation.
The study employs an innovative approach involving normothermic machine perfusion (NMP) – a technique that preserves livers on a machine under conditions similar to the human body. Specific drugs release fat from liver cells, filtered out of the perfusion machine, effectively reducing the liver’s fat content and enhancing its functionality.
The trial involves 60 livers from donors with a high risk of fatty liver disease, divided into two groups – one undergoing NMP alone and the other subjected to both NMP and the fat removal treatment.
The study’s primary goal is to establish the safety of this approach, potentially paving the way for more extensive studies exploring how fat removal can increase the number of successful transplants.
Notably, the preservation and defatting process conducted on the machine is expected to have no adverse effects or risks, as all defatting agents are thoroughly flushed from the liver before transplantation.
Professor Joerg-Matthias Pollok and Mr David Nasralla, leading the trial at RFH, expressed optimism about the study’s potential to expand the pool of viable livers for transplantation. With the rising rates of obesity contributing to the prevalence of NAFLD in the donor pool, innovative strategies like the DeFat study could revolutionise liver transplantation procedures, ultimately improving the outcomes and quality of life for individuals in need.
These two studies represent significant advancements in the field of liver transplantation.
Photo Caption - DeFat liver recruitment team pictured L-R: Mr Satheesh Iype, consultant surgeon, Mr Hussain Abbas, surgical research fellow, (Oxford University), Professor Joerg-Matthias Pollok, Mr David Nasralla, consultant surgeon, Mr Carlo Ceresa, locum consultant surgeon and Mr Navneet Tiwari, senior clinical fellow.
