mTOR inhibitor reduces nontumour-related death in liver transplantation for hepatocellular carcinoma

Abstract

Sirolimus is a regularly applied immunosuppressant for patients undergoing liver transplantation (LT) for hepatocellular carcinoma (HCC). Sirolimus not only significantly inhibits HCC recurrence but also protects renal function. However, the improvement effect of sirolimus on nontumour-related death in patients is still unknown. The aim of our study was to investigate the therapeutic effect of sirolimus on nontumour-related deaths. In this study, we retrospectively enrolled 403 LT patients with HCC from January 1, 2015, to December 31, 2018. The median follow-up time was 47.1 months. The patients were divided into the sirolimus group (N = 184) and the sirolimus-free group (N = 219). There were no significant differences between the sirolimus group and the sirolimus-free group in survival (P = 0.054). In transplant patients who exceeded the Milan or Hangzhou criteria, the sirolimus group achieved higher survival than the sirolimus-free group (P = 0.005; P = 0.02). Moreover, multivariate analysis showed that sirolimus strongly reduced the hazard ratio (HR) for nontumour-related death in LT patients who exceeded the Milan (HR: 0.42; 95% CI: 0.18-1; P = 0.05) or Hangzhou criteria (HR: 0.26; 95% CI: 0.08-0.89; P = 0.032). HCC recurrence increased the risk of nontumour-related death. In conclusion, sirolimus-based immunosuppression can significantly reduce nontumour-related death in LT patients who exceed the criteria for transplantation. In addition, this finding will further promote the application of sirolimus after liver transplantation for hepatocellular carcinoma.

Keywords: Hepatocellular carcinoma; Liver transplantation; Nontumour-related death; Sirolimus.

Fig. 1

Flowchart for screening patients

Fig. 2

Comparison of survival between the sirolimus group (N = 184) and sirolimus-free group (N = 219) among all patients (P = 0.054)

Fig. 3

Comparison of survival between the sirolimus group (N = 96) and sirolimus-free group (N = 109) among patients fulfilling the Milan criteria (P = 0.78) (a). Comparison of survival between the sirolimus group (N = 88) and sirolimus-free group (N = 110) among patients exceeding the Milan criteria (P = 0.005) (b). The distribution of causes of death in patients exceeding the Milan criteria was distinguished by sirolimus administration (c)

Fig. 4

Comparison of survival between the sirolimus group (N = 141) and sirolimus-free group (N = 166) among patients fulfilling the Hangzhou criteria (P = 0.3) (a). Comparison of survival between the sirolimus group (N = 43) and sirolimus-free group (N = 53) among patients exceeding the Hangzhou criteria (P = 0.02) (b). The distribution of causes of death in patients exceeding the Hangzhou criteria was distinguished by sirolimus administration (c)

Fig. 5

Comparison of survival between patients with (N = 130) and without hepatocellular carcinoma recurrence (N = 273) (P < 0.0001) (a). Distribution of causes of death, recurrence vs. nonrecurrence group (b)