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ILTS 2012 Report – Experts discuss balancing the risks with the benefits in liver transplantation
by Thomas R. Collins – With a scarcity of livers available for transplantation, there is a tremendous pressure on the medical community to make the best use of the organs that are transplanted. The last thing a transplant specialist wants to be accused of doing is wasting an organ.
At the same time, there is pressure to explore the frontiers of transplantation, to expand the bounds of what’s possible.
The question is how to balance the risk versus the potential benefits, which is a question explored in depth in a daylong symposium sponsored by Astellas Pharma held here at the 18th International Congress of the International Liver Transplant Society.
The symposium explored an array of topics, from when a prospective transplantation can be considered futile to the risks associated with transplantation in Hepatitis C patients to whether giving preference to the sickest patients is, ethically, the best approach to liver distribution.
Andrew Cameron, MD, PhD, Director of Liver Transplantation at the Johns Hopkins University School of Medicine, talked about the idea of futility — that even with a transplant, some patients still will fare poorly.
He emphasized that the MELD score measuring how sick a patient is doesn’t measure how well they’ll do following a transplant. He drew attention to the Survival Outcomes Following Liver Transplantation (SOFT) score, developed by a group of researchers at Columbia University. They examined 25,000 liver transplant cases to determine what was correlated with dying in the three months after transplant. They found that older age, having a previous transplant, and being on life support were among the things associated with poor results.1
“I think intuitively we all want to transplant — we all believe in the power of transplantation,” Dr Cameron said. “It may not be careful enough to tell a patient or their family, ‘They’re too sick for transplant, the MELD is too high. We’re not going to do it.’”
The key is to predict when transplants are likely to be unsuccessful, he said. Ways of coming up with numbers to measure this are evolving, but the expertise of individual centres and individual doctors will ultimately play a big role in tough decisions as well, Dr Cameron said.
“That’s the question: Can we identify when liver transplant is less successful and how can we quantify it?” he said. “I think when we talk about maximizing transplant benefit, you then are getting to a very good understanding of minimizing futility.”
Marina Berenguer, MD, of the Digestive Medicine Service at the Hospital Universitario i Polytecnico La Fe in Valencia, Spain, talked about whether it’s worthwhile to perform re-transplantation in Hepatitis C patients.
“I think it’s a good indication in appropriately selected candidates,” she said.
The largest transplant registries show five-year survival rates among HCV re-transplant recipients barely reaching 50 percent, Dr Berenguer said. That touches off debates over whether the use of scarce organs in these patients, for transplantations over and over again, is acceptable.
“The decision to re-transplant in HCV-affected patients in the current era of organ shortage is not only a controversial position,” she said, “it’s also an emotional decision.”
Dr Berenguer said that while it’s true that HCV patients getting re-transplanted have poor survival rates, the same is true for HCV negative patients.
She said that models that have been developed to assess risk, including the “Rosen score” and the donor risk index, can be useful in getting better results for HCV patients needing re-transplants. If donors at the lower end of the risk spectrum are involved, survival rates can be similar to non-HCV patients, at about 70 percent, she said.
“If we apply this model, we can improve our results,” she said.
As for the fear the Hepatitis C will simply recur after the transplant, that concern can be addressed as well, she said.
“We have learned over the years that this natural history of Hepatitis C can be modified, particularly by anti-viral therapy,” she said.
Mitra Nadim, MD, Associate Professor of Clinical Medicine at the University of Southern California Los Angeles, bemoaned the lack of good data in the United Network of Organ Sharing system for determining which patients should be considered for a simultaneous liver kidney (SLK) transplant.
There is a sore need for a sophisticated trial to try to develop a “usable algorithm” for these decisions, she said.
“The UNOS data does not capture any of the data to be able to move forward to make any kind of decision on policy,” she said.
A recent summit of experts on SLK, which Dr Nadim helped organize, said such a trial should collect data prospectively and try to answer questions such as what is the most effective, cost-effective tool to measure kidney disease and renal function, minimum glomerular filtration rates for SLK, and whether the aetiology of pre-transplant acute kidney injury affects post-transplant outcomes.
Sung-Gyu Lee, MD, PhD, Professor of Surgery and Director of Organ Transplantation at the Asan Medical Center in Seoul, Korea, said that ABO-incompatibility between donors and prospective liver transplant recipients should not be ruled out as an option.
“ABO incompatibility should not be regarded as a contraindiciation for adult LDLT,” he said in his presentation. “But, careful patient selection is needed to achieve acceptable outcomes.”
Since the most common complication in these cases is infection, more individualized immunosuppression protocols are needed for widespread use of this approach to transplantation, he said. That said, intrahepatic biliary stricture remains a complication without a remedy, and more research is needed to determine the factors that bring about this problem, so that it can be avoided.
He said, though, that living-donor exchanges show superior patient outcomes by overcoming the immunological hurdles.
“(The) propagation of exchange living-donor programme is limited by the sacrifice of emotional motivation between the donor and the recipient,” he said. Indeed, in Korea, just 1 percent of adult living donor liver transplant cases have been matched for exchanged paired donation. He said the approach is “feasible” nonetheless.
Neil Wenger, MD MPH, Professor in the Division of General Internal Medicine at the University of California Los Angeles and who does ethics consults there, said an allocation system in which the sickest patients rank highest might not be the best system.
“It’s really important to notice that there are many patients in the sicker age groups who have survival benefits that are below those of less sick patients,” Dr Wenger said. “This means very explicitly that if one is to use a MELD-only-based mechanism to allocate organs, you will unequivocally not use organs maximally to achieve years of life gained.”
Part of the reason for adhering to a sickest-first philosophy is the avoidance of regret, he said — if the sickest get transplanted, those less sick will still be alive and at least have a chance at a transplant.
“Never do we need to make the decision under those circumstances… that care is futile — or, even harder, it’s not futile, but the benefit achieved is not high enough so that that organ should be kept away from someone who might benefit more,” Dr Wenger said. “A very difficult decision to be made, but perhaps the societally correct one.”
An even more important consideration involved with the ethics of allocation is the continued, high-cost care of patients for whom there is almost no hope of a transplant, he said.
“It may be that this inefficacious use of society’s resources is actually far more important than the misallocation of organs by simply focusing on the sickest,” he said.
Allocation choices involve two principles set out by a group of U.S. and European internists in the “Medical Professionalism in the New Millennium” project — the primacy of the welfare of the patient in front of the doctor at any given time; and the principle of social justice, including fair distribution of healthcare resources.2
In the end, letting the public know the details of allocation decisions is critical, he said.
“In order to maximize the miracle of liver transplantation, at least from my perspective, we have a social responsibility both because we’re the ones who get to choose how the organs get allocated and also from a professional perspective,” Dr Wenger said. “And that requires transparency in building the best possible organ allocation mechanism. This means transparency concerning every organ, transparency concerning every patient, including those patients not on the list. And in that way we can maximize benefit to society.”
References:
- Rana A et al. Am J Transplant 2008 Dec; 8(12): 2537-46
- Meakins JL. J Am Coll Surg 2003; 196: 115-8
