On a more serious note, Organ Allocation in America: An Outsider’s View

Organ Allocation in America: An Outsider’s View

Vinay Kumaran, MBBS, MS, M Ch

Liver Transplant Surgeon, Mumbai, India

I did my fellowship in Transplant Surgery at the Thomas Starzl Transplantation Institute of the University of Pittsburgh Medical Center at a time when liver transplantation was in its infancy in India. I returned to India after my fellowship to become part of the first generation of liver transplant surgeons in India. Unlike the US, most liver transplants in India are living donor liver transplants, similar to the situation in Japan and Korea. The ethical issues are different and perhaps lets us look at the organ allocation system in the US with a fresh perspective.

I was in Chicago, attending the American Transplant Congress. I have in interest in liver transplantation for liver cancer. I wrote the Indian guidelines for liver transplantation for cancer a few years ago (1) (2). I was listening to Dr Ryutaro Hirose from UCSF describe the evolution of liver allocation for liver cancer in the US.

To summarize it briefly, in the early years of liver transplantation, patients with liver cancer were attractive candidates for liver transplant. They were not as sick as patients dying of liver failure but they were, just as surely, destined to die of their disease if they were not transplanted. They were more likely to survive the operation because they were not yet as sick as the liver failure patients. Unfortunately, it turned out that they had very high rates of recurrence of cancer in other parts of the body after transplant and rarely survived long term. Liver cancer became a relative contraindication for transplant. After all, it was better to perform a transplant on a patient who would survive for many years than to give the liver to someone who would be dead of recurrent disease in under a year. It was against this background that the liver transplant of baseball legend Mickey Mantle was seen as controversial. He seemed to have been given a chance which would not have been given to a less well known patient. As it happened, he had an early recurrence of cancer and the transplant did him no good, vitiating his last days with a massive operation and depriving another patient of the liver he received. In 1996, a paper from a liver transplant group in Milan (3), headed by Dr Vincenzo Mazzaferro, who also spoke in the same session at the American Transplant Congress, reported that if patients with liver cancer are carefully selected for transplant, they have excellent long-term survival. The selection was on the basis of the size and number of tumours seen on imaging (CT scan or MRI) done before transplant. The patient could have a single tumour up to 5 cm in diameter or up to 3 tumours, none of which were more than 3 cm in diameter. If these criteria, now known as the Milan Criteria, were adhered to then patients undergoing liver transplants for liver cancer would have a long term survival as good as patients undergoing liver transplants for cirrhosis without cancer. The problem now was that patients who met the criteria when they were listed for a liver transplant may not necessarily meet them at the time of transplant. If the wait for a liver was long, the tumours would grow and the patient would have to be taken off the list. The solution was to give them more points on the score used to allocate organs (the MELD score) so that they did not have to wait too long for the organs.

Dr Hirose’s presentation was about measures to make sure that patients with liver cancer do not have a disproportionate advantage over patients with liver failure, who may also die or become too sick to transplant while waiting for a liver. Measures such as tests for tumour behaviour (like AFP, a tumour marker measured in blood) and the possibility of making patients wait for 6 months before giving them extra points were discussed. The rationale was that patients who had aggressive tumours would have the tumours progress during these 6 months and they would no longer be eligible for transplant. Those who still remained within the criteria had well behaved, indolent tumours and would do well after transplant. A solution rather reminiscent of the Hunger Games. A Darwinian survival of the fittest.

A gentleman with a European accent stood up at the end of the presentation and pointed out that “what you are proposing is to do what is best for the liver, not what is best for the patient.” Dr Ryutaro did not quite seem to understand the point and segued into explaining that we have to make sure that organs are optimally utilized.

If we look at an outsider’s overview of liver transplantation in the US, the field comprises predominantly deceased donor liver transplants (livers donated by brain dead donors). This is a finite resource and the number of liver transplants being done has plateaued. Many patients waiting for a liver transplant die on the waiting list. Many more are removed from the waiting list when they become too sick to transplant. These also die soon but they do not show up on the ‘waiting list mortality’ statistic.

Very few centers offer living donor liver transplantation. This is partly because it is a technically more complex operation and there are very few surgeons in the US with the technical expertise and the experience to do these safely. This results in a vicious circle where the next generation of transplant surgeons is even less likely to get the training they require to perform this more demanding operation. The other reason, of course, is the fear of the consequences of a complication or mortality in a donor in a highly litigious society.

The best treatment for a patient with a liver cancer which is beyond the Milan criteria is still a liver transplant. A transplant still gives the patient a 50% chance of cure. No other treatment modality gives the patient more than a minuscule chance of surviving for 5 years. Similarly, watching a patient with liver cancer for 6 months to see which ones will have biologically indolent cancers will improve the results of transplantation but among those whose tumours progress will be some who could have been saved if they had a transplant immediately instead of waiting to see if the tumours would spread. Again what is best for the patient conflicts with what is best for the liver or for the transplant center.

What is the solution? Ideally the solution is the protocol used in India. If the cancer is low risk, the patient is offered both options, deceased donor liver transplant and living donor liver transplant (a family member volunteering to donate part of their liver to the patient). If the cancer is higher risk (beyond the Milan criteria, for instance), then deceased donor liver transplant is not offered but living donor liver transplantation remains on the table with an informed discussion with the patient and the donor about the risk of recurrence and the risk of death or complications for the donor. I do not believe I am ethically justified in refusing a living donor liver transplant to a patient who has a 50% chance of being cured by the operation as long as the donor understands the 50% risk of death due to recurrence or other reasons.

References

1. Role of liver transplantation for hepatocellular carcinoma. V, Kumaran. Suppl 3, 2014, J Clin Exp Hepatol, Vol. 4, pp. S97-S103.

2. The Indian National Association for Study of the Liver (INASL) Consensus on Prevention, Diagnosis and Management of Hepatocellular Carcinoma in India: The Puri Recommendations. Kumar A, Acharya SK, Singh SP, Saraswat VA, Arora A, Duseja A, Goenka MK, Jain D, Kar P, Kumar M, Kumaran V0, Mohandas KM, Panda D, Paul SB, Ramachandran J, Ramesh H, Rao PN, Shah SR, Sharma H, Thandassery RB and Task-Fo, (The INASL. Suppl 3, 2014, J Clin Exp Hepatol, Vol. 4, pp. S3-S26.

3. Liver transplantation for the treatment of small hepatocellular carcinomas in patients with cirrhosis. Mazzaferro V, Regalia E, Doci R, Andreola S, Pulvirenti A, Bozzetti F, Montalto F, Ammatuna M, Morabito A, Gennari L. 11, 1996, N Engl J Med, Vol. 334, pp. 693-9.