Primum Non Nocere

Authors


Corresponding author: Goran B. Klintmalm, gb.klintmalm@baylorhealth.edu

Abstract

It is time for the transplant community to develop a consensus on when the risk to the living donor is justified and when it is not, in relationship to the potential benefits to the recipient.

‘First do no harm’. The quote is ascribed to Galen (129AD–216AD), the famed physician from Pergamum in present-day Turkey. The undertaking of the first successful kidney transplant in 1954 by Murray and his colleagues (1) was a bold move based on the insight obtained by René Küss after the allograft kidney transplant he performed in 1951 (2). Yet, this by definition violated the principle of ‘First do no harm’. By using a homozygous twin the allogeneic immune response could be avoided. Later, the use of family donors was a prerequisite to obtain results necessary to allow the budding specialty to develop. The fundamental principal was that while removal of a kidney from a healthy donor ‘did harm’, it was inherently safe. A unilateral nephrectomy was the standard surgical treatment for any number of diagnoses and well understood. The surgical risk was extremely small and most importantly, the survival was dismal for patients with renal failure even when hemodialysis was available.

Liver transplantation was developed with deceased donors as the only source of liver grafts. When calcineurin inhibitors suddenly made the survival after liver transplantation likely (3), patients began to seek liver transplantation as the only realistic treatment for liver failure. With that the need for deceased donors rapidly grew surpassing the supply. The use of living donors for liver transplantation first came to the forefront when Silano Raia performed a partial hepatectomy on a live donor and transplanted the removed piece of liver in a pediatric patient in San Paulo 1988 (4). This procedure has become widely accepted, not only because the left lateral segmentectomy is a relatively small operation and quite safe, but also because of the scarcity of donors for small children.

The situation for adult liver recipients is quite different. First, a regular right or left hepatectomy is a large undertaking made even more daunting with the additional requirement placed on the surgeon to produce a piece of liver with intact vascular and biliary pedicals as well as liver mass sufficient to maintain life. It was presented at the Consensus Conference in Vancouver in September 2005 that the known worldwide mortality was 0.4% for right lobe donors and 0.1% for left lobe donors with a total of 14 deaths. In addition, two donors had undergone lifesaving liver transplants and one was in a persistent vegetative state (5). At the meeting in June 2007 of the International Liver Transplantation Society, Dr. Burchkhart Ringe reported that there were 12 known and an additional 16 possible cases worldwide (6). To this must be added the morbidity experienced in 38% of the donors, as reported by the A2ALL Study (7). Other unintended social consequences including prolonged absence from work, insurance denial and psychological issues are poorly understood with 12% of donors taking psychiatric medication and 17% having no medical coverage as reported by Genyk at the American Transplant Congress in May 2005 (8). Thus, the situation is much different in living donor liver transplantation when compared to living donor kidney transplantation and violating the principle of ‘do no harm’ is less justifiable.

Clearly, one must hold the urgency for a living donor to at least the same standards as a deceased donor. In 2005, the Scientific Registry of Transplant Recipients (SRTR) reported that the likelihood of recipient death from transplant-related complications was substantially higher if the recipient had a MELD score of 14 or less than if not receiving a transplant (MELD 6–11, HR 3.64 and MELD 12–14, HR 2.35). Once the recipient's MELD score was 15 or more, a liver transplant improved the likelihood for the patient to live 1 year or more (9). Consequently, since 2006, UNOS rules have mandated that livers be offered to all patients with MELD scores of 15 or more across the region before allowing livers to be used for local recipients with a MELD score of 14 or less. In spite of this, while attending scientific sessions on living donor liver transplantation during national and international meetings, we are informed that the recipients’ MELDs were 13, 12 or even 6 (10,11) or that the recipients had tumors well outside accepted criteria believed to justify the use of a deceased donor (12).

With the SRTR data on transplant benefits in mind, how can anyone justify exposing living donors to the risks of morbidity and mortality when recipients have a MELD of less than 15? The only exception would be for hepatic tumors and then only to recipients with an acceptable long-term outcome such as those within Milan (13), or at least San Francisco or Dallas criteria (14,15). That the patient has advanced liver disease is not enough to subject the donor to the risks. The death of a donor can never be considered the same as losing a patient on the waiting list. The patient suffers from a lethal disease, while the donor does not. Not 20, 30 or even 50 patients dying on the waiting list for a transplant can justify the death of a single healthy donor.

Circumstances may be different in countries where deceased donors are less or not available. However, regardless of geography, it is imperative to balance the risk to the healthy living donor versus the recipients’ risk of dying from disease. It is time for the transplant community to develop a consensus on when, during the recipients’ disease progression, the risk to the donor is justified and conversely, when the risk to the donor is not justified. Even in antiquity the physicians understood that the guiding principle for medical care is Primum Non Nocere.

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