Maintenance immunosuppressive therapy in liver transplantation: results from CESIT study, an Italian retrospective cohort study

Abstract Introduction Post-liver transplantation immunosuppressive therapy typically involves the combination of various drugs: calcineurin inhibitors (tacrolimus-TAC or cyclosporine-CsA), with the potential addition of mycophenolate-MMF or mTOR inhibitors with/without corticosteroids. This study aimed to investigate the use of immunosuppressive treatments and compare their risk-benefit profiles in clinical practice. Methods This retrospective multicenter cohort study integrated data from the national transplant information system and administrative claims data from 4 Italian regions. All adult patients who underwent incident liver transplantation between 2009 and 2019 were identified and categorized into two groups: cirrhosis or hepatocellular carcinoma-HCC. The trend of immunosuppressive treatment over the years was analyzed, and their effectiveness/safety profiles were compared using multivariate Cox models (HR;95%CI). Results The study comprised 785 subjects in the cirrhosis cohort and 1,196 in the HCC cohort. Over the study years, there was a decline in the use of CsA, while combination therapy involving TAC with other drugs increased compared to monotherapy. Overall, TAC-monotherapy use was slightly over 40% in both groups, followed by TAC+MMF (39.5%-cirrhosis; 30.6%-HCC) and TAC+mTORi (8.5%-cirrhosis; 13.3%-HCC). No significant differences emerged in risk-benefit profile of different TAC-based therapies, except for a higher risk of mortality in cirrhosis subjects under TAC-monotherapy compared to TAC+MMF (HR: 2.07;1.17-3.65). Conclusions The study highlights a shift over time in post-liver transplant therapeutic patterns, favoring the use of TAC in combination with MMF or mTORi, rather than monotherapy. Moreover, a potential association between TAC-monotherapy and increased mortality in the cirrhosis cohort was identified. Further research is warranted to optimize treatment strategies for liver transplant recipients.