Withdrawal of Immunosuppression in Liver Transplantation Seoul, Korea. Among them, we selected five patients (4.8%) who had a very low tacrolimus trough level (< 1 ng/mL by Liquid Chromatography-Mass Spectrome- try/MS). Four of them had frequently refused to take the immunosuppressive drug; they were interviewed to confirm the noncompliance. Finally, four patients weaned due to noncompliance and one patient weaned due to life threatening posttransplant lymphoproliferative disorder (PTLD) were enrolled. The median age at transplantation was three years (range, 8 months to 9 years). The primary diseases were biliary atresia (n = 2), neonatal hepatitis of unknown cause (n = 1) and hepatocellular carcinoma (n = 2). Four patients received living-related liver transplan- tation from their parent and one patient received a cadaver transplant. All five patients underwent immunosuppression induced with a steroid and tacrolimus regimen during the early stage of liver transplantation and were maintained on tacrolimus-based immunosuppression. Monitoring of graft function was followed by blood tests to assess liver function. In cases of abnormal findings in the blood tests, suspicion of rejection, a liver biopsy was performed. We reviewed the medical records and analyzed the clinical characteristics of the patients who discontinued immunosuppression, and retrospectively evaluated the immunologic relationship with their donor (blood type), immunologic status of a specific virus at pre-transplan- tation [Ebstein-Barr Virus (EBV), cytomegalovirus (CMV)], time between transplantation and immunosup- pressant withdrawal, follow-up period after immunosup- pressant withdrawal, episodes of rejection, and graft function. In addition, we attempted to confirm their histological graft status by performing a liver biopsy in two of the patients 64 and 32 months after withdrawal of immunosuppression. RESULTS Four patients received the liver transplantation from a parent donor and one patient from a cadaver donor. The immu- nosuppression regimen was steroid and tacrolimus treatment for a median of six months (range, 2 months to 9 months) after transplantation, followed by maintenance with tacrolimus for a median of 38 months (range, 4 months to 53 months) (Fig. 1). During the maintenance period, all patients had stable liver function. Three patients were treated with pulse steroid therapy and dose up tacroli- mus therapy when there was suspicion of acute rejection; two patients were confirmed to have acute rejection by liver biopsy within a month after transplantation. None of the five patients had rejection episodes for over 1 year (range, 14 months to 82 months) after withdrawal of the immunosuppression. Among the five cases, there were ABO blood type-iden- tical grafts in three cases and compatible grafts in two. Three patients were EBV high-risk (EBV seronegative recipients from EBV seropositive donor); one of them developed life threatening gastrointestinal PTLD and was weaned off immunosuppression 14 months post-trans- plantation. All five patients were CMV IgG positive pre- transplantation; there were no complications associated with CMV infection throughout the follow-up after trans- plantation (Table 1). A trial of withdrawal of immunosuppressant was started a median of 45 months after transplantation (range, 14 Fig. 1. Immunosuppressant regimens and withdrawal process. Table 1. Characteristics of the Subjects Case Age at Diagnosis Sex No. transplantation 1 Biliary atresia F 2 yrs 2 Neonatal hepatitis M 8 months 3 Biliary atresia M 3 yrs 4 HCC (HBV) M 9 yrs 5 HCC (HBV) M 8 yrs Donor Father Mother Father Father Cadaver Blood type (R/D) O+ / O+ (identical) B+ / O+ (compatable) A+ / O+ (compatable) B+ / B+ (identical) O+ / O+ (identical) EBV risk group High High Low High Low Pre LT CMV status (IgG / IgM) (± / -) (+ / -) (+ / -) (+ / -) (+ / -) HCC, hepatocellular carcinoma; R, recipient; D, donor, EBV, Ebstein-Barr Virus; CMV, cytomegalovirus. EBV high-risk group: EBV-seronegative patients receiving allograft from EBV-seropositive donors. EBV low-risk group: EBV- seropositive recipient or EBV-seronegative patients receiving allograft from EBV-seronegative donors. Yonsei Med J http://www.eymj.org Volume 50 Number 6 December 2009 785