The VITTAL Clinical Trial

• Over 8,500 people die each year from chronic liver disease in the UK.
• The NHS rejects 1 out of 5 livers that are donated because they are not considered to be of good enough quality to be used.
• The VITTAL study wanted to help with this problem by using Liver Perfusion to see if more livers can be made available for patients.

Chronic liver disease in the UK is rising every year, a result of obesity and increasing alcohol misuse. For patients who have end-stage liver disease (liver failure), a transplant is the only hope for survival, but demand for donated livers suitable for transplantation far outstrips supply.

According to NHS Blood and Transplant after a year on the NHS list for a liver transplant, 8% of patients had died while still waiting for a chance to have this life-saving operation.

A growing proportion of donated livers are coming from donors with a history of alcohol misuse, obesity or elderly people who also have other health conditions. These types of livers tend to be of lower quality and most of them cannot be used for transplantation.

In Liver Perfusion, the donated liver is placed in a machine containing a special warm temperature bath (called 'normothermic' conditions). The liver's blood vessels are washed through continuously with donated blood containing fresh oxygen, medications and nutrients.

The idea is to simulate the normal warm environment of a liver working in the body as closely as possible while connected to the perfusion device, and to see if with this treatment the liver can go on to be transplanted into a patient.

The UK research team based in Birmingham used a special machine called a Normothermic Machine Perfusion (NMP) device to objectively assess 31 NHS-rejected ‘marginal’ quality livers, to find out which of them were functioning well enough to be safely be used for transplantation in volunteer study participants.

Full study name: Viability Testing and Transplantation of Marginal Livers (called VITTAL for short). IRAS study identifier number: 206074 for the official review and approval of clinical trials research.

Chief Investigator: Professor Darius Mirza (Consultant Transplant Surgeon at the University Hospitals Birmingham NHS Foundation Trust and Honorary Professor at the University of Birmingham).

Principal Investigator: Mr Hynek Mergental (Consultant Surgeon at the University Hospitals Birmingham NHS Foundation Trust Liver Unit and Honorary Senior Lecturer at the University of Birmingham). 

Follow up : 5 year follow up on the initial study results: 

Discarded livers tested by normothermic machine perfusion in the VITTAL trial: Secondary end points and 5-year outcomes. Liver Transplantation30 (1):p 30-45, January 2024. | DOI: 10.1097/LVT.0000000000000270. https://pubmed.ncbi.nlm.nih.gov/38109282/ Mergental, Hynek; Laing, Richard ; Kirkham, Amanda ; Clarke, George; Boteon, Yuri L.; Barton, Darren; Neil, Desley A.H.; Isaac, John R.; Roberts, Keith J.; Abradelo, Manuel; Schlegel, Andrea; Dasari, Bobby V.M.; Ferguson, James W.; Cilliers, Hentie; Morris, Chris; Friend, Peter J; Yap, Christina; Afford, Simon C.; Perera, M. Thamara P.R.; Mirza, Darius F   

The main results publication of the VITTAL study can be read online and accessed for free in the leading international journal Nature Communications. Read the main VITTAL results article Publication title: Transplantation of discarded livers following viability testing with normothermic machine perfusion. Published 16 June 2020, lead author Mr H Mergental.

Summary Abstract of this Nature Communications article (publisher: Springer Nature; copyright © 2020 the Authors):

• There is a limited access to liver transplantation, however, many organs are discarded based on subjective assessment only. Here we report the VITTAL clinical trial (ClinicalTrials.gov number NCT02740608) outcomes, using normothermic machine perfusion (NMP) to objectively assess livers discarded by all UK centres meeting specific high-risk criteria.
• Thirty-one livers were enroled and assessed by viability criteria based on the lactate clearance to levels ≤2.5 mmol/L within 4 h. The viability was achieved by 22 (71%) organs, that were transplanted after a median preservation time of 18 h, with 100% 90-day survival. During the median follow up of 542 days, 4 (18%) patients developed biliary strictures requiring re-transplantation.
• This trial demonstrates that viability testing with NMP is feasible and in this study enabled successful transplantation of 71% of discarded livers, with 100% 90-day patient and graft survival; it does not seem to prevent non-anastomotic biliary strictures in livers donated after circulatory death with prolonged warm ischaemia.

Further information about the VITTAL study and its results is available for free on the government's online registry ClinicalTrials.gov (VITTAL study ID number: NCT02740608). Read more information about VITTAL 

We are extremely grateful to the patients who volunteered to participate in the VITTAL study. Without them stepping forward to volunteer, this ground-breaking research could not have been done.

We also wish to thank the following for their invaluable advice and assistance in the co-production of the VITTAL trial documents, summary of results and dissemination plan:

• Patient contributors from the Liver & GI Patient and Public Involvement Group (supported by the NIHR Birmingham Biomedical Research Centre) and
• Laura Chapman, Patient & Public Involvement and Engagement Manager for the NIHR Birmingham Biomedical Research Centre.