Chemoembolization decreases drop-off risk of hepatocellular carcinoma patients on the liver transplant list

Abstract

Introduction: The drop-off risk for patients awaiting liver transplantation for hepatocellular carcinoma (HCC) is 22%. Transplant liver availability is expected to worsen, resulting in longer waiting times and increased drop-off rates. Our aim was to determine whether chemoembolization can decrease this risk.

Patients and methods: Eighty-seven consecutive HCC patients listed for liver transplant (Milan criteria) underwent statistical comparability adjustments using the propensity score (Wilcoxon, Fisher's, and chi-square tests). Forty-three nonchemoembolization patients and 22 chemoembolization patients were comparable for Child-Pugh and Model for End-Stage Liver Disease scores, tumor size and number, alpha fetoprotein (AFP) levels, and cause of cirrhosis. We calculated the risk of dropping off the transplant list by assigning a transplant time to those who dropped off (equal probability with patients who were on the list longer than the patient in question). The significance level was obtained by calculating the simulation distribution of the difference compared with the permutations of chemoembolization versus nonchemoembolization assignment of the patients. Kaplan-Meier estimators (log-rank test) were used to determine survival rates.

Results: Median follow-up was 187 ± 110 weeks (range 38 to 435, date of diagnosis). The chemoembolization group had an 80% drop-off risk decrease (15% nonchemoembolization versus 3% chemoembolization, p = 0.04). Although survival was better for the chemoembolization group, it did not reach statistical significance. Two-year survival for the nonchemoembolization and chemoembolization group was 57.3% ± 7.1% and 76.0% ± 7.9%, respectively (p = 0.078).

Conclusions: Chemoembolization appears to result in a significant decrease in the risk of dropping off liver transplant list for patients with HCC and results in a tendency toward longer survival.

Fig. 1

DoTx or drop off for all patients in our study with HCC fulfilling Milan criteria. Among the 52 who were not treated with chemoembolization (top graph), 7 (13.5%) dropped off the transplant list (dark lines) at various times. In the subgroup that was treated with chemoembolization, (bottom graph), there was only 1 patient (3%) who dropped off the transplant list

Fig. 2

Kaplan–Meier survival curves (time in months). There was no statistically significant survival difference between the nonchemoembolization (dashed) and chemoembolization (solid) groups. Survivals are from date of listing. Two-year survival for the nonchemoembolization group was 57.3% ± 7.1% and for the chemoembolization group was 76.0% ± 7.9% (p = 0.078 from DoL). Although the median survival has not been reached yet, it appears to be >5 years. Vertical bars are 95% confidence intervals

Fig. 3

Percent risk of dropping off the liver transplant list for patients with list time longer than (t) versus time spent on the transplant list (t). When all comparable patients from both groups were considered (t = 0, n = 65), the drop-off risk for the chemoembolization group was 3% compared with 15% for the nonchemoembolization group. The difference is statistically significant (p = 0.04). As waiting time gets longer, fewer patients are included in the risk calculation, and risk differences become statistically nonsignificant, i.e., p continuously increases

Fig. 4

Non-drop-off probability as estimated by the Kaplan–Meier method, for the treated and untreated groups. The number of patients at risk for drop off are indicated on the curves. The log-rank test was used for comparison (p = 0.159)