Introduction: This retrospective study was done to assess our experience of Everolimus rescue therapy for steroid resistant rejection after liver transplantation.

Materials and Methods: Among 218 patients who underwent liver transplantation at Ulsan University Hospital during the period between April 2007 and October 2020, 44 patients received Everolimus as one of the post-transplant immunosuppressants. The indications for Everolimus was for renal protection in 23, immunologic causes in 13 and others in 8. Among the 13 patients who received Everolimus to control their suspected immunologic events, 7 patients were confirmed to experience steroid-resistant rejection. The effectiveness of Everolimus to rescue the steroid resistant rejection in these 7 patients was evaluated by the biochemical response, that is normalization of AST and ALT. The time point after liver transplantation when AST/ALT elevation drew medical attention and the value of AST/ALT at the time, implementation of liver biopsy and the result especially expressed as rejection activity index, use of steroid pulse therapy (SPT), time elapsed from liver biopsy to SPT, SPT to use of Everolimus, use of Eveolimus to normalization of AST and ALT, respectively were investigated.

Results: The time point after liver transplantation when AST/ALT elevation drew medical attention vary widely from 15 days to 46 months after the liver transplantation and the mean value of AST and ALT at the time was 145 IU/L and 254 IU/L, respectively. Liver biopsy was performed in all patients and mean rejection activity index was 4.6. Steroid pulse therapy (500 mg/day, fixed dose for 3 days consecutively) was given to all the patients, two times in one patient. Everolimus was given because AST/ALT levels were not stabilized from 3 days to 51 days (median, 8 days) after the end of SPT. The mean values of AST/ALT were 146/310 IU/L and were higher than the values before SPT. It took a mean of 127 days (range, 31 ~ 360 days) for AST stabilization and 175 days (range, 51 ~ 390 days) for ALT stabilization. All the 7 events of SRR were amenable to Everolimus rescue therapy at a median of 91 days when evaluated by AST and ALT normalization.

Conclusion: Steroid-resistant rejection after liver transplantation was amenable to Everolimus treatment. Everolimus was induced at a median of 8 days after steroid pulse therapy. It took a median of 91 days for AST and ALT normalization for Everolimus rescue therapy. For generalization of the results of this study, a randomized controlled study in a large cohort is needed.