A Risky Business

By John Lake, MD

Professor of Medicine and Surgery, Departments of Medicine and Surgery, Director, Liver Transplantation Program, University of Minnesota Medical Center, University of Minnesota Medical School, Minneapolis

In the U.S., there are currently more solid organ transplants performed using live donors than deceased donors (1). This trend represents the rapid growth in live-donor kidney transplantation. The reason for this growth in live-donor kidney transplantation is that the outcomes are substantially better using kidneys from live versus deceased donors and currently wait-times for a kidney in the country can be more than five years. Importantly in this regard, survival after kidney transplantation is substantially better than survival on dialysis.

Thus, a very compelling argument can be made to aggressively pursue live-donor kidney transplantation. Quite frankly, if I needed a kidney transplant, there is little doubt that I would aggressively pursue potential live donors.

However, it is difficult to make a similar compelling argument for live-donor liver transplantation. Heretofore, the results of live donor liver transplantation have not yielded superior graft survival rates as compared to deceased donor transplantation (2). This is particularly true when accounting for the fact that live donors are younger, there is virtually no cold ischemia time and the recipients tend to be healthier.

In the U.S., while the number of kidney transplants using live donors has continued to rise, the number of live-donor liver transplants that are performed annually has remained relatively flat (1). This is in spite of the fact that the total number of liver transplants performed has recently begun to increase again. The reasons why the live-donor liver transplants have remained relatively flat reflect three things.

First, donor morbidity is substantial and mortality is not inconsequential, particularly when compared to live-donor kidney transplantation.

Second, the need for live-donor liver transplantation is uncertain.

Finally, the number of recipients for whom a live donor ultimately comes forward and is judged acceptable is relatively limited (3).

In terms of morbidity and mortality — make no mistake about it — the risks are substantial. It is likely that as many as 10, or even more, donors have died as a result of liver donation worldwide (4). A recent study from the Adult-to-Adult Living-Donor Liver Transplantation (A2ALL) study group (5) examined complications following live-donor liver transplantation.

In a cohort of more than 400 patients, 13 experienced either an aborted donation or a situation where the graft was removed but not transplanted because of recipient complication on the operating room table. In the group of aborted transplants, there were a number of important complications, including one case of intra-operative hypotension and a bile leak in another case leading to bacteremia and an intra-abdominal abscess.

More than 10 percent of the patients required re-hospitalization following donation, including 14 who required two or more re-hospitalizations.

A total of 38 percent of the patients experienced complications specifically related to donation, including 17 percent who experienced two or more complications. These included 49 donors, or 12.5 percent of the cohort who experienced infection, largely bacterial; four experiencing inter-operative injury; and six other inter-operative complications.

The most common complication was a bile leak, which occurred in approximately 10 percent of donors. Twenty-two, or 5.6 percent, of the donors experienced an incisional hernia; 2.3 percent developed an intra-abdominal abscess; 3.3 percent experienced either prolonged ileus or bowel obstruction; and bleeding was reported in 1.5 percent of donors. Twenty-seven, or 7 percent, of live donors experienced a cardiopulmonary complication, 16, or 4 percent, developed hypoxia. four percent had psychological complications, three patients developed ascites, two developed portal vein thromboses and one an IVC thrombosis.

In terms of severity of these complications by the Clavien severity grading system, a total of 11, or 2.8 percent, experienced either grade 3 or 4 complications. Overall, more than a third of adult live donors experienced complications after donation. Many of them required significant intervention, and some could have resulted in disability or been regarded as representing a life-threatening condition.

Moreover, this is only a partial picture, as the long-term morbidity is unknown. The one thing we know for sure is that, while liver regeneration is rapid and impressive after live donation, it is often incomplete and some patients can have on-going thrombocytopenia.

It also is clear that live-donor liver transplantation is not appropriate for all potential liver transplant recipients (6). Experience has shown us that the most critically ill patients, such as those with fulminant hepatic failure, those transplanted from the ICU, or those with high MELD scores (i.e >25) do not do well with live-donor transplantation.

In addition, a recent study from the Scientific Registry of Transplant Recipients showed that patients do not attain the survival benefit in the first year following their liver transplantation until their MELD score is greater than 18 (7).

Thus, the “window of opportunity” for live-donor liver transplantation is relatively small, i.e MELD scores 15-25, if one is going to focus live- donor liver transplantation on those who are most likely to benefit from a survival perspective.

Finally, the major argument against live-donor transplantation is the lack of growth of live-donor liver transplantation in the U.S. Indeed, there has been no increase (and, in fact, a decrease) in live-donor liver transplant volume since the year 2001 (1), with still only 323 live-donor liver transplants performed in 2005 (contrasted with 6,120 deceased-donor transplants).

Indeed, only ~5 programs in the country do more than 20 live-donor liver transplants per year. This is important, as a recent report from the A2ALL group has shown that there is a learning curve for live-donor liver transplantation, such that the results of live-donor transplants are not comparable to deceased-donor transplantation until more than 20 cases are performed

By comparison, there are 17,469 patients on a waiting list and almost 6,000 deceased-donor liver transplants performed each year. Moreover, it is estimated that perhaps as many as 1,000 organs suitable for liver transplantation are wasted because no so-called “suitable recipient” or accepting program is available.

These data raise a serious question as to whether there is indeed a need for live-donor liver transplantation in this country and perhaps we should focus our efforts on maximally using the deceased donors we have available. By the numbers, this approach could more than make up for the number of organs that are obtained from live donation.

In summary, live-donor liver transplantation is a risky business. It is associated with a high rate of potential complications, with generally worse results and clearly contributes little to alleviating the “perceived” donor shortage. Moreover, it is quite clear that if we maximally utilized every potential organ in this country, we could generate more than three times the number of grafts that come from live donors.

Finally, it is important to emphasize that live donation is probably the only situation in which someone undergoing surgery does not directly benefit from the surgical procedure. To not violate the principal of “physician do no harm” requires extraordinary proof that such a procedure is required. At this point in time, it is difficult to say that this principle has indeed been met.