Interview conducted by April Cashin-Garbutt, BA Hons (Cantab)
Please can you give a brief introduction to liver transplantation?
Liver transplantation is a surgical procedure in which a liver (or part of a liver) is removed from a donor and placed into a recipient. Although some transplants use a portion of the liver of living donors, the vast majority of donors are deceased.
Liver transplant is life saving and is the only treatment option for many patients with liver failure, liver cancer, and a variety of other ailments. More than 70% of patients remain alive 5 years after their transplant. In 2012, more than 5,000 liver transplants were performed in the US.
How does organ availability place constraints on the transplant community?
More than 1,000 patients die on the transplant list each year waiting for a liver; the supply of donor livers is the limiting factor in the number of procedures that can be performed. We rely mostly on livers from deceased donors (as opposed to living relatives or friends), so it is essential that we maximize the number of deceased organ donors.
To this end, the transplant community has tried to expand the donor pool by using more “extended criteria donors”. This group includes older donors, donors with fatty livers, and donation after cardiac death (DCD) donors. DCD donors are those who undergo organ procurement shortly after the breathing machine and blood pressure medications are stopped and after the heart stops beating. This is in contrast to standard donation after brain death (DBD), in which the donor is declared brain dead, and the lungs and heart continue to get supported during the organ procurement process.
What features does a high quality donor liver have?
The issue of donor quality is an important one, because we know that donor factors can impact the outcomes for recipients after transplant. Many studies have been performed looking at this question, and there are many factors that can be considered markers of a “high quality” donor. After transplant, patients do better if the liver donor was young and had brain death following trauma. Other issues are important as well.
Fatty liver, which is strongly associated with diabetes, obesity, and metabolic syndrome, is becoming increasingly common, and studies suggest that up to 1/3 of adults in the US have fatty livers. Donor livers with more fat in them tend to do worse after transplant, so these livers are typically judged to be low quality.
Another big issue is that livers from DCD donors also don’t do as well after transplant. This may be because the surgeons have to wait a few minutes after the heart stops beating before procuring organs, so the liver is not receiving blood flow for a period of time prior to procurement. This is not an issue for brain dead donors, because the heart and lungs are supported during the procurement.
What are the main reasons why a donor liver may be unused?
We all want the absolute best outcomes for our patients, so when an organ is judged to be of poor quality, transplant centers can refuse to use the liver to avoid a bad outcome and complications after the transplant. So there are many factors that are weighed in the decision to use or not use a liver, and many have to do with the quality of the donor.
Our study, using US national transplant data, looked at the characteristics of organ donors whose livers were not used, and not surprisingly, increasing donor age, diabetes, obesity, and DCD were all associated with non-use. The data do not reliably record fatty liver, but we surmise that diabetes and obesity were markers of fatty liver. Interestingly, from 2004 to 2010, non-use of DCD donor livers increased four-fold. This probably reflects the accumulating experience that DCD livers are in fact worse than standard DBD livers.
How has the availability of high quality donor livers changed over recent years?
The diabetes and obesity epidemics are impacting the public health in many ways, and organ donation and transplantation is yet another example. Fatty liver is becoming a leading cause of severe liver disease and cirrhosis and is accounting for more and more of the patients who need a transplant.
On the donor side, fatty liver is also becoming more common. We found in our study that the number of organ donors with diabetes and obesity is increasing and that organ donors are, on average, getting older. So more of our donors have “low quality” livers.
We also found that the number of donors who are DCD has increased, while the number of standard DBD donors has actually decreased. How, or even if, these two trends are related is not really known.
How does this compare to the availability of other donor organs?
There is a shortage of all solid organs, and demand is not being met for any group. Kidneys may be the best comparison group. Although the above factors also affect the quality of donor kidneys, the impact of some of these factors may not be as great. For instance, DCD kidneys may not be as good as standard kidneys, but they probably do better than DCD livers, so DCD is not as big of a deal for the kidney transplant community.
What do you think is the reason for the downward trend in the availability of high quality donor livers?
The aging population and the obesity and diabetes epidemics are clearly responsible for much of the trend in quality and liver availability. The other big emerging issue is DCD. We found that between 1995 and 2010, the percentage of donors who were DCD increased from 1% to 11%. When we combined that with the increasing reluctance to use DCD, we found that DCD accounted for more than a quarter of liver non-use in 2010.
If DCD was simply being used to expand the existing donor pool, this wouldn’t matter. The problem is that standard DBD is decreasing. We don’t know why this is happening. Some have suggested that doctors are getting better at neurological management, so we are avoiding brain death in more patients. Others have hinted that donors who are not yet brain dead are being taken off of life support and used as DCD donors before they have had time to progress to brain death. But the truth is that we really don’t know.
What impact has this trend had?
The total number of liver transplants performed in the US has been declining since 2006. Lower donation rates are responsible for some, but not all, of the decline. Increasing non-use of donated livers is contributing to the declining numbers of transplants as well. This may become more problematic as demand for livers continues to increase.
How can the donor pool be increased and are there any plans in place to achieve this?
Many of the strategies to increase the donor pool have focused on increasing extended criteria donation and DCD. These strategies may be helpful for the kidney transplant community, but unfortunately, these are the very livers that are likely to go unused and therefore may not improve our capacity to perform more liver transplants. Currently, work is under way to try to improve outcomes for these lower quality livers, for instance through better organ preservation techniques after liver procurement. Of course the best way to increase the donor pool is simply to get more people to agree to become organ donors.
Are there any dangers of using more inferior organs?
The stakes can be high for liver transplant recipients. Patients who receive low quality donor livers are more likely to develop complications with their bile ducts, which are the tubes that drain bile from the liver into the intestines. Such complications can lead to infections and liver graft damage. Studies have shown that these patients are more likely to develop graft failure. Patients who receive such livers may also incur longer hospital stays and increased costs.
How far do you think we are from being able to transplant bionic organs?
There is a lot of research being conducted looking at xenotransplantation, which is the transplantation of organs from one species to another. For instance, a promising approach would be transplanting a pig liver into a human. Given the ongoing shortage of donor livers, this would be a boon to the liver transplant community. Unfortunately, many barriers to this type of treatment exist and much more research needs to be done before this will become a reality.
Where can readers find more information?
Our recent study and the accompanying editorial can be found here: http://onlinelibrary.wiley.com/doi/10.1002/lt.v19.1/issuetoc
More information on organ transplantation and donation can be found here: http://www.unos.org
Would you like to make any further comments?
The decision about whether or not to use a particular donor liver can be a difficult one, and both donor and recipient factors and individual preferences play important roles. Our work is a simplification of some of these issues, but the overall trends in donor quality are concerning, particularly given the on-going declines in transplant volume.
About Dr Eric Orman
Eric S. Orman, MD, is a board-certified gastroenterologist and fellow in Transplant Hepatology in the Division of Gastroenterology & Hepatology at the University of North Carolina, Chapel Hill. He is currently enrolled in a Master’s program in Clinical Research at the UNC Gillings School of Global Public Health, which is funded by an NIH-sponsored training grant. His clinical and research interests are in the care and complications of patients with cirrhosis and end-stage liver disease.