The VITTAL Clinical Trial

VITTAL is a major research study that investigated the effectiveness of an exciting new technique called Liver Perfusion.

The Birmingham-based research team wanted to test Liver Perfusion as an innovative way of checking and improving the function of donated livers in the laboratory, so that they can then be considered for use in transplantation. 

The aim of the VITTAL clinical trial was to find out if Liver Perfusion could increase the numbers of livers available for use in life-saving transplantation operations in the future. Liver Perfusion is done using a technology called Normothermic Machine Perfusion (or NMP for short).

The results showed that this new technique could save up to 7 in 10 donor livers that would otherwise be rejected.

Why more livers are needed for transplantation

  • 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.

How Liver Perfusion works

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 aims of the VITTAL Study

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). 

 How the VITTAL research was done

  • 31 donated livers that had been rejected by the NHS were each put into an NMP machine for 4-6 hours of perfusion treatment in the laboratory. How well they were functioning was closely monitored throughout.
  • 22 livers successfully met the strict study rules for being good enough to use. The 22 livers were then transplanted into 22 volunteer patients with their fully informed prior consent.
  • The participants’ health and wellbeing was then carefully checked and followed-up by our specialist medical team at the Queen Elizabeth Hospital in Birmingham over two years.

The results of the VITTAL Study

Liver Perfusion could save 7 in 10 rejected donor livers

  • We found that of the 31 perfused livers, 22 of them (71%) could be safely transplanted into patients. All of these livers would previously have been considered too risky to use.
  •  The first 90 days after transplant is the critical period for a new liver to settle in. We found that all 22 (100%) of the VITTAL patients transplanted were well and their new livers were fully working at Day 90. At 12 months after surgery all 22 patients (100%) remained well, and 21 of the 22 new livers (96%) were working fully.

Funded by the Wellcome Trust, the VITTAL team of experts from the University of Birmingham’s Centre for Liver and Gastrointestinal Research, University Hospitals Birmingham NHS Foundation Trust and the NIHR Birmingham Biomedical Research Centre found that just 4-6 hours of Liver Perfusion enabled 70 per cent of currently discarded livers to recover enough to allow successful transplantation into a recipient.

This could significantly increase the supply of livers available for NHS transplant and reduce waiting list times for patients. Further larger studies are now needed to confirm the results and develop the use of this new technology in clinical care. 

Publications from the VITTAL Study

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 ( 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 (VITTAL study ID number: NCT02740608). Read more information about VITTAL 

Special thanks to our research participants and the public

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.