Jee Hyun Lee, et al. Table 2. Outcome after Weaning of Immunosuppression Time between Cause of IS Maintenance Case No. LT and withdrawal IS weaning 1 Noncompliance Tacrolimus 60 months 2 PTLD Tacrolimus 14 months 3 Noncompliance Tacrolimus 60 months 4 Noncompliance Tacrolimus 45 months 5 Noncompliance Tacrolimus 41 months Follow-up after IS withdrawal 64 months 82 months 32 months 14 months 29 months Rejection* (n) 0 1 1 0 0 The last AST / ALT / GGT (U/L) 28 / 25 / 10 33 / 26 / 32 23 / 14 / 24 28 / 17 / 12 21 / 12 / 16 IS, immunosuppressant; AST, aspartate aminotransferase; ALT, alanine aminotransferase; GGT, gamma glutamyl transferase. *Rejection before weaning of immunosuppression. Table 3. Comparison of Favorable Clinical Markers for Withdrawal of Immunosuppression Suggested factors for withdrawal in the previous studies Subjects included in this study Author Favorable markers Case1 Case2 Case3 Case4 Case5 > 5 years post-LT O X O X X Devlin, et al. Non-immune mediated liver disorders O O O O O Incidence of early rejection (n) 0 1 1 0 0 > 2 years post-LT O X O O O Long-term normal graft function O O O O O Takatsuki, et al. > 1 year without rejection after withdrawal O O O O O LDLT O O O O X Pediatric case O O O O O % 40 100 - 80 100 100 80 100 LDLT, living-donor liver transplantation. months to 60 months), and the period of follow up after weaning from the immunosuppressant was a median of 32 months (range, 14 months to 82 months). None of the five patients had rejection episodes after withdrawal of immu- nosuppression; four of them maintained normal graft function for longer than 3 years (median, 38 months; range, 4 to 53 months) (Table 2). There was no case of an immune-mediated primary liver disease. Two of the four noncompliant patients (patient 1 and 3) were intentionally weaned from their medication. The main reason for weaning off the immunosuppression was parents’ anxiety about the complications from immunosuppression therapy. The other two noncompliant patients (patient 4 and 5) had taken the medication irregularly. These two older children refused to take the life-long medication. We compared these five patients with previous reports to determine the favorable clinical markers and selection criteria for discontinuation of immunosuppression (Table 3). Devlin, et al.2 and Takatsuki, et al.3 reported on the withdrawal of immunosuppression, including pediatric liver transplant recipients, and analyzed the favorable markers for successful withdrawal of immunosuppression and the selection criteria for elective weaning. The five patients reported here had non-immune mediated liver disease, long-term maintenance of normal graft function without rejection and were all pediatric recipients. Exclud- Fig. 2. Liver histologic finding in one patient at 32 months after withdrawal of the immunosuppressant. Hepatic lobular architecture is well preserved showing focal balooning degeneration. Portal space displays intact bile ducts with no inflammatory infiltrate. Mild periportal fibrosis is found (original magnification × 200, Masson Trichrome). ing the one patient with PTLD, four patients attempted to wean the immunosuppressant treatment two years post- transplantation. We performed a liver biopsy in two of our patients at 64 months and 32 months after withdrawal of the immu- nosuppressant to rule out chronic rejection in spite of their normal liver function. The histological findings of their grafts showed normal hepatic architecture without any evidence of acute cellular or chronic rejection (Fig. 2). DISCUSSION Tolerance is defined as the clinical situation when a graft 786 Yonsei Med J http://www.eymj.org Volume 50 Number 6 December 2009