Posttransplant Outcomes in Older Patients With Hepatocellular Carcinoma Are Driven by Non-Hepatocellular Carcinoma Factors

Abstract

The incidence of hepatocellular carcinoma (HCC) is growing in the United States, especially among the elderly. Older patients are increasingly receiving transplants as a result of HCC, but the impact of advancing age on long-term posttransplant outcomes is not clear. To study this, we used data from the US Multicenter HCC Transplant Consortium of 4980 patients. We divided the patients into 4 groups by age at transplantation: 18 to 64 years (n = 4001), 65 to 69 years (n = 683), 70 to 74 years (n = 252), and ≥75 years (n = 44). There were no differences in HCC tumor stage, type of bridging locoregional therapy, or explant residual tumor between the groups. Older age was confirmed to be an independent and significant predictor of overall survival even after adjusting for demographic, etiologic, and cancer-related factors on multivariable analysis. A dose-response effect of age on survival was observed, with every 5-year increase in age older than 50 years resulting in an absolute increase of 8.3% in the mortality rate. Competing risk analysis revealed that older patients experienced higher rates of non-HCC-related mortality (P = 0.004), and not HCC-related death (P = 0.24). To delineate the precise cause of death, we further analyzed a single-center cohort of patients who received a transplant as a result of HCC (n = 302). Patients older than 65 years had a higher incidence of de novo cancer (18.1% versus 7.6%; P = 0.006) after transplantation and higher overall cancer-related mortality (14.3% versus 6.6%; P = 0.03). Even carefully selected elderly patients with HCC have significantly worse posttransplant survival rates, which are mostly driven by non-HCC-related causes. Minimizing immunosuppression and closer surveillance for de novo cancers can potentially improve the outcomes in elderly patients who received a transplant as a result of HCC.

Figure 1. Demographic and clinical features of elderly patients transplanted for HCC

a. Histogram showing age distribution at the time of transplantation in patients with HCC. b. Proportional distribution of patients stratified by 5-year increments over age 65 years. c. Median age (± 95% CI) at transplantation stratified by UNOS regions. d. Changes in sex distribution with increasing age in patients with HCC e. Changes in etiologic factors for HCC with increasing age. ALD = alcoholic liver disease, HCC = hepatocellular carcinoma, NASH = non-alcoholic steatohepatitis, UNOS = United Network for Organ Sharing

Figure 2. Tumor-specific Attributes in Elderly Patients Transplanted for HCC

a. Changes in Milan staging with increasing age in patients with HCC. b. LRT distribution comparison in older patients with HCC. c. Changes in pathologic T staging with increasing age in patients with HCC. HCC = hepatocellular carcinoma, LRT = Locoregional Therapy

Figure 3:. Long-term post-transplant clinical outcomes in patients transplanted for HCC

a. Overall survival stratified by age groups in patients transplanted for HCC. b. Time to Recurrence stratified by age groups in patients transplanted for HCC HCC = hepatocellular carcinoma, OS = overall survival, RFS = recurrence-free survival

Figure 4. Competing Risk Analysis for the Impact of Age on HCC-Related and Non-HCC-Related Death

CI = confidence interval, CIF = cumulative incidence function, HCC = hepatocellular carcinoma