Calcineurin inhibitors, including both tacrolimus and cyclosporine, have been associated with a dose-dependent increase in the posttransplant risk of HCC recurrence.6 Conversely, sirolimus has shown anticancer properties in in vitro and animal models, both alone or in combination with doxorubicin or sorafenib.7–12 Sirolimus find more can

prevent angiogenesis by interfering with vascular endothelium growth factor (VEGF)-mediated pathways in endothelial cells, thus limiting the growth of tumors,7 and also impacts established tumors, by inducing extensive microthrombi and so inhibiting tumor growth.9, 13 Although these animal data are clear, clinical studies are less convincing. We have demonstrated good outcomes with the use of sirolimus in a noncontrolled trial, and more recently the groups at the University of Colorado in Denver and Fudan University in Shanghai demonstrated better survivals in patients on sirolimus compared to control liver recipients.4, 14–16 Although all show similar trends, these retrospective studies included limited numbers of patients, and possible confounding variables could not be taken into account buy LGK-974 due to the limited sample size. The present study is based on a large registry transplant population and evaluates the impact of immunosuppression on survival in an attempt to define the best posttransplant

treatment combination for HCC patients. AFP, alpha fetoprotein, HCC, hepatocellular carcinoma; HBV, hepatitis B virus;

HCV, hepatitis C virus; HR, hazard ratio; Astemizole HRSA, Health Resources and Services Administration; MELD, Model for End-Stage Liver Disease; OPTN, Organ Procurement and Transplantation Network; SRTR, Scientific Registry of Transplant Recipients; TTV, total tumor volume; UNOS, United Network for Organ Sharing. This study analyzed data from the Scientific Registry of Transplant Recipients (SRTR). The SRTR data system includes data on all donors, wait-listed candidates, and transplant recipients in the United States, submitted by the members of the Organ Procurement and Transplantation Network (OPTN), and has been described elsewhere.17 The Health Resources and Services Administration (HRSA), US Department of Health and Human Services, provides oversight to the activities of the OPTN and SRTR contractors. The study was reviewed and approved by the Health Research Ethics Board at the University of Alberta. The study population included all adult (≥16 years) patients who received an isolated liver transplantation from March 2002 to March 2009. In order to ensure that all subjects had a significant exposure to the drugs, only individuals kept on the same maintenance immunosuppression protocol for at least 6 months posttransplant (or until death) were further selected. Overall, 25,201 out of 39,859 patients receiving a liver transplant during the study period were excluded.