Drug trial to improve early liver function in transplantation Royal Free & UCL Partners Liver Transplant Programme, & UCL Medical School (Barry Fuller)

A little bit of Biology and Chemistry Oxygen is ‘the Life Force’ It helped us evolve. It’s the Energy which makes all parts of our bodies function well. The Energy available from Oxygen is amazing (But there is a trade-off – no free lunch!)

Liver One of the largest organs in the human body It constitutes only 2-3% of the body mass, but it accounts for 20-30% of the total oxygen consumption (similar oxygen use to Brain – which tells us something about how active our livers are to keep us healthy!)

The Trade-Off with oxygen Our liver cells use large amounts of oxygen energy to keep the complex functions working To get the energy out of Oxygen, our liver cells have to push Chemistry to the Limit, strip out the Energy and make water, and keep it all Under Control ‘Almost’ like splitting the atom Liver has its’ own mini Power Plant in every cell – mitochondria – (the dark dots)

There’s no Free Lunch with Oxygen Our livers get the energy they need But - in the process, some oxygen gets changed to an Uncontrolled form – Free Radicals – which interfere with body processes Normally our liver cells, (and in fact all our body organs) mop up the Free Radicals with Antioxidants – so we stay Healthy – Young and Old alike

In Transplantation, the new Liver needs to Kick-Start its’ control of Oxygen Energy straight-away, and Antioxidants may be important to help. But it takes time to digest many of the natural antioxidants, so this is too slow There are some fast-acting antioxidants based on sulphur, which can be dissolved in water and delivered as a drug, and we have access now to a new one (Bucillamine – shown on the right) which is more than twice as effective as the previous ones. Bucillamine has been used in Japan for many years for rheumatoid arthiritis, but not in transplants

The Liver Transplant Bucillamine Trial Currently, the plans are being looked at by the Medical Research Council and the Medicines & Health Regulatory Agency to ensure they are happy with the plan. Two UK Centres, Royal Free and Leeds Explain to patients and ask Consent before they join the trial Randomised and hidden (‘blinded’) from assessors A dose of Bucillamine introduced into the blood supply of the new liver as soon as it is transplanted A lower dose given with the Intra Venous fluids which are part of the normal transplant operation, continued for the first 3 hours and then stopped. Information to be analysed by top Clinical Trials Units in UCL and Leeds

We hope that Bucillamine will help to speed early recovery in Liver Transplantation, (And if so, may be useful for other types of liver disease, and even in other transplants such as kidney transplant) Do you have any questions?