Introduction: Concerns about the side effects of steroid use in liver transplantation have led to the development of steroid-free regimens. At our hospital, the standard immunosuppressive therapy for blood group compatible liver transplantation is a combination of two drugs, calcineurin inhibitor (CNI) and steroids, or three drugs with mycophenolate mofetil (MMF) added to reduce the nephrotoxicity of CNI. However, due to concerns that perioperative administration of steroids for viral diseases may cause a flare-up of the underlying disease after liver transplantation, we introduced steroid-free immunosuppressive regimen in 2001, and have reported on its efficacy. In this study, we report the short- and long-term results of steroid-free immunosuppressive regimen.
Subjects and methods: The subjects were liver transplant recipients who underwent liver transplantation at Osaka university hospital in Japan from 1999 to 2023, excluding ABO-incompatible liver transplants. The steroid-free (Fr) group received 20 mg of basiliximab on the day of liver transplantation and on the fourth postoperative day in addition to CNI and MMF, and no postoperative steroids were administered. Eight patients who received 1 gram of methylprednisolone only intraoperatively and one patient who received daclizumab instead of basiliximab and did not use steroids were also included in the Fr group. The steroid use (St) group included the administration of steroids in addition to CNI and MMF.
Results: This study included 165 patients, age 50±12 years, 84 males (50.9%), 136 living donor liver transplant recipients (82.4%), and 29 deceased donor liver transplant recipients (17.6%). There were 40 patients (24.2%) in the Fr group and 125 (75.8%) in the St group. Primary disease was viral 100% in the Fr group vs. 39.2% in the St group (p<0.01); Patients in the Fr group were older at transplant (55.7 vs. 48.1 years, p<0.01) and had lower MELD scores (16.0 vs. 22.5, p<0.01); CMV antigenemia was lower in the Fr group (13 patients (32.5%) vs 66 (52.8%), p=0.062). The frequency of acute cellular rejection (ACR) (6 (15.0%) vs. 14 (28.6%), p=0.204), 10-year survival (77.0% vs. 70.0%, p=0.10), and de novo malignancies (9 (22.5%) vs. 17 (13.6%), p=0.273) were not significantly different between the two groups.
Conclusion: Steroid-free immunosuppressive therapy was able to maintain induction of immune tolerance without increasing postoperative acute rejection and de novo malignancies.