Balancing the Risks of the Elderly Donor With Recipient Benefits in LDLT

[Clark]

http://onlinelibrary.wiley.com/doi/10.1111/ajt.13019/full

Balancing the Risks of the Elderly Donor With Recipient Benefits in LDLT
C.-L. Chen*
Article first published online: 20 OCT 2014
DOI: 10.1111/ajt.13019
American Journal of Transplantation

The high priority accorded to donor safety in living donor liver transplantation (LDLT) leads to exclusion of many potential donors. Age is a surrogate marker for health, and potential donors above 60 years are often excluded because of the perceived higher risk of donor complications and suboptimal recipient outcomes. As the donor pool is chronically insufficient, and because the aging population in many countries has resulted in increased number of elderly donors, many transplant centers now evaluate potential donors of up to 65 years of age [1]. Kim et al [2] present a case report of an LDLT in this issue of the journal, where both the donor and recipient are septuagenarians. The implications of extending the limits for donor age in LDLT are significant, and need to be examined carefully.

There are no widely accepted age criteria for donor exclusion in LDLT, mainly because the chronologic age of the liver does not accurately reflect its physiological function. A 97-year-old donor liver has been reported to be utilized in deceased donor liver transplantation (DDLT) with good long-term follow up. But this is an exception rather than the rule, and numerous studies have shown that donor age is the most significant donor variable affecting recipient outcomes in DDLT [3]. The D-MELD score, a well-regarded predictive scoring system in DDLT, is obtained by multiplying the recipient Model for End-Stage Liver Disease (MELD) score and donor age. Old age grafts have been associated with increased graft complications and decreased recipient survival. This is attributed to the effect of age on numerous signalling pathways and progenitor cells in the liver, which adversely affects protein synthesis, bile excretion, and liver regeneration [4]. These grafts are also more susceptible to injury caused by prolonged ischemic time followed by reperfusion.

Unlike in DDLT, risk factors such as ischemic times and graft steatosis can be better modulated in LDLT, and these should ensure better recipient outcomes. Still, grafts from elderly donors may affect short-term regeneration in recipients and long-term regeneration in donors [5]. Shin et al [6] showed that the larger the gradient between age of elderly donor and younger recipient, the poorer were the graft survival and recipient outcomes. On the other hand, many studies have shown that with proper selection, it is feasible to have excellent recipient outcomes with grafts from elderly donors of up to 65 years of age. Studies conducted on donors aged less than 70 years have found similar complication rates to younger donors, but the rate and severity of donor complications seem higher when the remnant liver is less than 35% of total liver volume [7].

Should the septuagenarian recipient receive liver transplantation at all? Older recipients with hepatocellular carcinoma are likely to have lower survival rates compared to younger patients, and this may be worth considering when considering organ allocation in DDLT patients. However, the liver graft is a gift intended for a particular recipient in LDLT, and the septuagenarian recipient may be excluded on the basis of poor performance status, comorbidites and high MELD score, not on the basis of age alone [8].

What issues need to be addressed, to ensure optimal outcomes with old age donors in LDLT? Selecting the elderly donor for LDLT requires accurate judgment of the physiological tolerance for a major hepatectomy. The potential addition in life expectancy of the recipient should be balanced against the donor risks before proceeding ahead. Thorough evaluation of these donors is required, especially for cardiovascular and cerebrovascular risk factors and occult malignancy. Extensive involvement of the donor and recipient in the decision-making process should be ensured. The institution may consider a separate review system for such extreme cases to ensure balanced decision making. Nowadays, there is broad agreement that in LDLT, graft volume to recipient standard liver volume ratio should be at least 35%, and remnant liver should be at least 30% of total liver volume of donor. These margins of safety may need to be higher in the elderly, to compensate for the diminished regenerative capacity of the liver. The indication for transplant and recipient disease severity may need to be evaluated keeping the chronologic age of the graft in mind. For example, procuring a graft from an elderly donor for a stable young recipient may not have the best outcomes for either of them, but an elderly donor for a critically ill old recipient may be justified. Furthermore, transplant centers need to be prepared for the likelihood of higher incidence of donor complications and even mortality due to the inherent risks associated with this age group.

The authors of the case report in this issue of the journal have made it clear that choosing a septuagenarian as the donor was the last resort. Donor safety should not be compromised for better recipient outcomes in LDLT. It is important to identify and mitigate the risks of the elderly donor who may undergo major hepatectomy for LDLT. However, it is possible that similar situations shall arise with increasing frequency, in view of increasing life expectancy and decreasing birth rates around the world. This example should not be emulated without considering in-depth the consequences to the donor, recipient and the field of LDLT.