Liver transplantation in those of advancing age: The case for transplantation

Longevity in the developed world continues to increase. In the United States from 1950 to 2005, those 65 to 75 yr of age increased twice as much as the overall annual growth rate of the population while those >75 yr increased 2.9 times as much.1 Projections indicate that the rate of growth by 2050 for older age groups will continue to increase more than twice as rapidly as the total population (Fig. 1). It is expected that older patients will continue to seek advanced medical treatments as they age. How will this effect liver transplantation (LT)?

Figure 1. Growth in population of older Americans: The population of people in the United States 65 yr and older will continue to increase in the first half of this century. It is estimated that by 2050, 9% of the population will be 65-74 yr while 11.6% will be 75 yr and older.1

Abbreviations

LT, liver transplantation; MELD, Model for End-Stage Liver Disease.

As longevity has increased, so has the burden of liver disease in those of advancing age.2 As of October 27, 2006, there were 2,075 patients 65 yr or older on the United Network for Organ Sharing waiting list.3 Similarly, the numbers of aged liver recipients has also increased. In 1988, 29 patients of age 65 or older underwent LT in the United States; in 2005, this number was 628, a 2100% increase (Fig. 2).3

Figure 2. Liver transplant recipients greater than 65 yr in the United States. The number of both waitlist patients and liver transplant recipients greater than 65 yr of age continues to increase at a steady pace. In 2005, 628 patients who were older than 65 years received a liver transplant.3

In this issue of Liver Transplantation, Cross et al. describe a series of patients from the King's College Hospital in London who underwent LT in the 7th decade of life. In a retrospective study from a prospectively maintained database, the authors compared the outcome of recipients aged 60 to 64 yr with those ≥65 yr at the time of transplantation. Results were further compared with a time-matched group of adult patients 18 to 59 yr old. Outcomes demonstrated no significant difference in survival for all 3 groups at 30-days, 1-yr, and 5-yr after LT; graft survival was similar to patient survival. However, the mean Model for End-Stage Liver Disease (MELD) score for those ≥65 yr was less than the other 2 cohorts. In addition, the indications for transplantation were different in the groups: the oldest cohort had significantly fewer recipients with hepatitis C and significantly more with primary biliary cirrhosis than the groups 60 to 64 yr and 18 to 59 yr. It is well-known that survival rates for patients transplanted for primary biliary cirrhosis are better than for other indications.4 This, along with lower MELD scores, may have, in part, led to improved graft and patient survival in the older cohorts.

The issue of LT in patients >60 has been addressed in multiple reports from other centers.5–13 Survival at 3-yr posttransplantation has ranged from as low as 35%6 to as high as 83%.9 At the University of California, Los Angeles (UCLA), we found no statistically significant difference in survival after LT for a group of 62 patients over 70 yr of age when compared to a younger cohort of recipients of age 50 to 59 yr old (in press). These reports of transplantation in the elderly are important in an era of increasing donor shortage particularly when the balance between justice and utility for organ allocation continues to be actively debated.14 It is the philosophy of most centers that organs should be given to patients with the most years of life to gain, and, when asked, the public tends to agree.15 However, it is not unrealistic for a 65-yr-old adult with minimal comorbidities living in a developed country to expect to live an additional 20 yr. At the present time, there is no established chronological age limit for organ transplantation, and individual centers set their own rules based on the concept of “physiologic age,” which is not completely defined.

In the United States, 10% of all adults die on the liver transplant waiting list.16 The situation is expected to worsen throughout this decade as more patients with hepatitis C, hepatocellular carcinoma, and decompensated cirrhosis,17 in addition to greater numbers of those over 60 yr are added. This, in part, will lead to longer waiting times and delays from listing to time of transplantation, ultimately translating into deaths of intended recipients unless the number of donor organs increases. Undoubtedly, this will lead to further debates and revisions in policies regarding the optimal allocation policies.18, 19

The current report breaks new ground with the emphasis on extensive screening, particularly for cardiovascular disease. All patients ≥60 yr underwent electrocardiographic evaluation, echocardiography, and coronary arteriography. As cardiovascular complications represent a significant cause for mortality in aged transplant recipients, the prognosis is considered to be highly dependent on programs for screening and modification of these risk factors. This extensive cardiovascular screening for patients over 60 and 65 yr likely selected out the better-risk older recipients from those more likely to do poorly postoperatively. This is reflected in the lower unmodified MELD scores of the group 65 yr and older (mean 12.2) compared to the other groups (15.8 in patients 60 to 64 yr, 16.5 in patients 18 to 59 yr). With such screening procedures in place, the authors found that the most common cause of death in the group older than 65 yr was malignancy, while cardiovascular disease was the most common cause of death in those under 65 yr. Such extensive cardiovascular screening is important and stratifying patients based on cardiovascular risk is appropriate. However, according to accepted guidelines for preoperative testing, clinical evaluation and noninvasive stress testing is sufficient to identify patients at high-risk for cardiovascular disease.20 Performing angiography in all liver transplant recipients over 65 yr may be overkill. Thus, the cost-effectiveness of the strategy outlined by the authors needs to be questioned.

Equally important is extensive psychosocial screening of potential elderly recipients. It is essential that a social support network be present for elderly recipients of liver transplants. It is expected that older adults will need greater support than those of younger age groups.

Finally, the authors demonstrated a lower incidence of acute rejection episodes in the 2 older cohorts. A similar phenomenon has been found in kidney transplantation.21, 22 Causes of graft failure with advancing age tend to be less likely related to acute rejection,23 with more elderly patients likely to die with a functioning allograft.

Although this study by Cross et al. strengthens the argument for transplantation of elderly liver recipients who have been appropriately screened and have a strong psychosocial network, however, it does not address quality of life issues of these patients after LT. Other analyses do demonstrate improvement in posttransplantation physical health and health-related quality of life in liver transplant recipients in general.24 However, this has not been extensively examined in older liver transplant recipients. These multiple reports demonstrate that older patients can successfully undergo LT, and now it is time to have a formal assessment of health-related quality of life in assessing the overall health status of these patients. Such sophisticated measures will determine their quality of life and the quality-adjusted life-years gained for these patients; such calculations can be used to assess the relative value of LT relative to other health care procedures25 in terms of cost/benefit.

In summary, this study demonstrates that those older than 60 yr can successfully undergo LT with patient and graft survival similar to younger adult patients. This data will add important information to the debate on who can and should undergo LT. As the waiting list continues to grow, unless there is growth in the number of donor livers, there will continue to be debate about rationing and donor/recipient matching for this limited resource. A purely utilitarian policy is unlikely to be accepted but issues regarding transplantation of the aged are likely to be examined with greater scrutiny. While this study provides important data that support the concept that age should not be a sole criterion for transplant candidacy, new and more sophisticated measures are required at this time if we are to continue to perform transplantation in elderly adults with this limited resource.