Association between everolimus combination therapy and cancer risk after liver transplantation: A nationwide population-based quasi-cohort study

The potential of everolimus (EVR) in reducing hepatocellular carcinoma (HCC) among recipients following liver transplantation has been reported. This nationwide population-based quasi-cohort study investigated whether combining EVR with calcineurin inhibitor therapy affects the risk of HCC and extrahepatic cancers compared to a time duration–matched cohort of recipients not receiving EVR. Using data covering the entire population from Korea, liver transplant recipients who had initiated immunosuppressants between June 2015 and February 2020 were included, and divided into 2 groups: the EVR combination and noncombination groups. We calculated adjusted hazard ratios (aHRs) and absolute risk reduction for the risk of HCC and extrahepatic cancer with EVR combination therapy using a Cox regression model. A time duration–matched retrospective cohort of 932 recipients in both of the groups was identified. The EVR combination group showed a lower risk of HCC (aHR, 0.53; 95% confidence interval, 0.30-0.94) and extrahepatic cancers (aHR, 0.30; 95% confidence interval, 0.14-0.63) compared to the noncombination group. The absolute risk reduction was 0.004 for HCC and 0.012 for extrahepatic cancer. The findings suggest that adding EVR to calcineurin inhibitor therapy reduces cancer risk in liver transplant recipients, highlighting the importance of considering cancer risk when choosing immunosuppressive therapies.