Association between Everolimus Combination Therapy and Cancer Risk after Liver Transplantation: A Nationwide Population-based Quasi-Cohort Study.

Abstract

The potential of everolimus in reducing hepatocellular carcinoma (HCC) among recipients following liver transplantation has been reported. This nationwide population-based quasi-cohort study investigated whether combining everolimus with calcineurin inhibitor therapy affects the risk of HCC and extrahepatic cancers compared to a time-duration-matched cohort of recipients not receiving everolimus. Using data covering the entire population from Korea, liver transplant recipients who had initiated immunosuppressants between June 2015 and February 2020 were collected and divided into two groups: the everolimus combination and non-combination groups. We calculated adjusted hazard ratios (aHRs) and absolute risk reduction (ARR) for the risk of HCC and extrahepatic cancer with everolimus combination therapy using a Cox regression model. A time-duration-matched retrospective cohort of 932 recipients in both of the groups was identified. The everolimus combination group showed a lower risk of HCC (aHR, 0.53; 95% confidence interval [CI] 0.30-0.94) and extrahepatic cancers (aHR, 0.30; 95% CI 0.14-0.63) compared to the non-combination group. The ARR was 0.004 for HCC and 0.012 for extrahepatic cancer. The findings suggest that adding everolimus to calcineurin inhibitor therapy reduces cancer risk in liver transplant recipients, highlighting the importance of considering cancer risk when choosing immunosuppressive therapies.