Older Age Alone Found No Bar to Liver Transplantation

LONDON, Oct. 3 -- Five-year survival rates for liver transplant patients 60 and older matched rates for younger patients and the older patients had fewer rejection episodes, researchers here found.

Patients age 60 or older had one-year and five-year survival rates following liver transplantation that were not statistically different from those of younger patients and they experienced fewer rejection episodes (P = 0.0016), Michael A Heneghan, M.D., of King's College Hospital here, and colleagues reported in the October issue of Liver Transplantation.

An increasing number of patients are undergoing assessment for liver transplantation, but the number of available organs has not increased, so patient selection criteria are being reevaluated, the researchers said.

Older patients have long been considered high-risk recipients because they may have comorbidities and an increased risk of death related to both hepatic and nonhepatic causes. On the other hand, the researchers said, immune senescence may be a potential advantage for these patients, making rejection less likely.

To examine transplantation for patients in their seventh decade, the researchers undertook a retrospective study from a prospectively maintained database, comparing outcomes for a series of patients given a transplant at King's College Hospital from 1988 to 2003.

All patients were given cadaver grafts. Recipients received immunosuppression according to the protocol of the time, with earlier recipients receiving cyclosporin-based triple therapy, and later recipients given tacrolimus (Prograf)-based dual therapy.

The researchers compared the outcome of 77 patients older than 65 (mean age 67) with that of 137 recipients 60 to 64 (mean age 62), and 202 time-matched control patients with chronic liver disease, ages 18 to 59 (mean age 42).

Survival at 30-days for all three groups was not significantly different: 99%, 94%, and 94%, respectively (P not significant).

Survival at one year in the three groups was 82%, 86%, and 83%, respectively (P not significant). At five years, survival was still comparable at 73%, 80%, and 78%, respectively (P not significant).

More rejection episodes occurred in the younger patients, the researchers reported.

Episodes of acute cellular rejection were fewer in both older cohorts (43% and 45% versus 61% respectively, P = 0.0016), although there was no significant difference in the number of patients in each group who experienced acute cellular rejection (P = 0.16).

A similar but nonsignificant trend was found for rates of chronic rejection among the groups, the researchers reported.

These data suggest that survival of patients in their 60s after liver transplant is satisfactory, at least in the first five post-procedure years. In addition, older patients experienced less rejection, with those over 65 experiencing the least, and had good graft survival, Dr. Heneghan and his colleagues said.

The researchers theorized that the older recipients are more rigorously assessed for comorbidities that could affect the outcome. Additionally, their better survival may reflect the greater proportion of patients with primary biliary cirrhosis, well recognized as a successful cohort for transplant.

A further explanation could be that patients older than 65 had a lower MELD score (model for End-Stage Liver Disease), a predictor of post-transplant survival.

The researchers noted, however, that currently, the MELD score is not used for organ acceptance in Britain. Instead, the Child-Turcotte-Pugh scores were used, and outcome scores were not statistically different among the groups.

Among patients who did not survive, cardiovascular causes were most common for patients younger than 65, while malignancy and infection were the major causes for older patients.

The study was limited, the researchers noted, by the absence of serial or protocol liver biopsies, so that the prevalence of mild cellular rejection may have been underestimated.

The patients also came from only one medical center and were not etiology matched. Also, it was not possible to determine the prevalence of disease recurrence in this cohort, nor could different immunosuppressive regimens be compared, they said.

As a result of these findings, the researchers wrote, a liver transplant should not be denied to older patients on the basis of age alone, following a comprehensive screen for comorbidity.

Because of their lower rejection rates and excellent graft survival, older recipients might benefit from strategies geared toward immunosuppression withdrawal and tolerance induction. However, long-term follow-up of these patients is warranted, they said.

In an accompanying editorial, Ronald W. Busuttil, M.D., Ph.D., and Gerald S. Lipshutz, M.D., of the University of California, Los Angeles, wrote that in the U.S. alone, 10% of all adults die on the liver-transplant waiting list.

The situation is likely to worsen, they said, as the number of patients with hepatitis C, hepatocellular carcinoma, and decompensated cirrhosis increases and the population ages.

The current study, they said, adds important information to the debate about who should be given a liver transplant. For example, they said, at UCLA they found no statistically significant differences in survival after transplant for 62 patients older than 70 compared with recipients 50 to 59 years old.

At the present time, they said, there is no established chronological age limits for organ transplantation, and individual centers set their own rules.

While age should not be a sole criterion, "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," they concluded.

They pointed out that all patients 60 and older in this study 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 years likely selected out the better risk older recipients from those more likely to do poorly postoperatively," they wrote.