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Green Templeton College | Oxford

Nasralla

David Nasralla, DPhil student in Surgical Sciences at Green Templeton College, recently had his research published in the journal Nature. His work, 'A randomized trial of normothermic preservation in liver transplantation', which he co-wrote with Professor Peter Friend, has now also been cited by outlets such as BBC News and The Times. The story was also featured on the cover of the May edition of Nature. David had the following to say about his research:

As part of my surgical career I elected to read for a DPhil under the supervision of Professor Peter Friend at Green Templeton College; this has proven to be one of the best decisions I ever made and has resulted in opportunities and accolades I never expected when embarking on this endeavour back in November 2013. Prior to this I worked for 10 years as a doctor in the NHS; a system designed for service provision rather than recognising individual contributions. Research proved a welcome alternative to this unrelenting pace; there were many times where it seemed just as tough and thankless, although I always had the option of retreating to the GTC library.

My research has been concerned with the mechanisms that underlie the efficacy of normothermic machine perfusion (NMP) in liver transplantation, the bulk of which involved setting up and conducting a multinational randomised controlled trial. The current standard method of liver preservation is in an ice box; here the liver is flushed with a cold preservation solution before being packed in ice (static cold storage; SCS) where it remains for the duration of its preservation until the surgeon is ready to transplant it. In recent years there has been a substantial increase in the number of organ donors, but most of these additional donors are considered high risk; either elderly with multiple co-morbidities or have diseased livers. Standard storage in an ice box is often inadequate for these organs as they tolerate preservation at these temperatures poorly and there is no way to assess the organ's quality.

During NMP the liver is perfused with oxygenated blood, medications and nutrients at normal body temperature and so is preserved in a functioning physiological state. This helps to repair some of the cellular injury that occurs during the retrieval process and also enables an objective assessment of the functioning organ to be made during its preservation. The trial I conducted aimed to establish whether the use of NMP was beneficial for the transplant recipient when compared with SCS, using early release of liver enzymes as a validated surrogate for longer term graft and patient survival. It took almost two years to transplant all of the 220 patients required to power the study, with the pace of recruitment increasing exponentially as transplant units gained experience and confidence in the technology. I was on call continuously throughout the recruitment period, attending most of the NMP liver retrievals and transplants and overseeing the technicians who attended the SCS livers. I had returned to clinical practice by the time 1 year follow up was complete, and the results were compelling.

The study demonstrated that livers preserved using NMP showed better early function despite being preserved for substantially longer durations and with fewer of the livers being discarded after retrieval. Shortly after the completion of recruitment to the trial I presented the preliminary results at a Nuffield Department of Surgery event. I was subsequently approached by a Nature editor enquiring as to whether we would consider submitting our manuscript to them. This was something that I had not previously considered; Nature is not usually associated with clinical publications. But once this opportunity presented itself we pursued it strongly, never really sure whether it would lead to something tangible. After four rounds of intensive edits, the manuscript was provisionally accepted. This, however, was followed by two further rounds of extensive formatting, something for which Nature is renowed. Eventually, having completed this work, we also received the incredible news that it was to feature on the Nature cover, eventually being published on 3rd May.

For me, research has proven to be a better opportunity than I ever expected - my work has been widely presented, won several international prizes and opened up countless doors that were previously firmly shut. Had you asked me 10 years ago whether I was interested in doing a DPhil the answer would have been a resounding no. But to look back now over the past 5 years I couldn't envisage a path that could have been more enjoyable, satisfying and beneficial in an area of surgery that I love. My aim now is to remain actively involved with clinical research, hopefully through an enduring link with the University, for the foreseeable part of my surgical career.

The full manuscript can be found here. Special thanks to Prof Peter Friend, the members of the Consortium for Organ Preservation in Europe, the clinicians at all the transplant centres involved and, of course, the donors and their families.

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