【Objective】We investigated the efficacy and safety of mizoribine (MZR) for treatment-resistant rejection after a living-donor liver transplantation (LDLT) under an immunosuppressive regimen of tacrolimus (Tac) and low-dose steroids.
【Methods】Thirty patients who suffered acute cellular rejection (group M: moderate rejection, n=11; group S: severe rejection, n=7; and group R: treatment-resistant rejection, n=12) were treated additionally with MZR at 2―3 mg/kg/day. Blood cell counts and blood chemistry were followed after the start of MZR.
【Results】In all groups, the levels of transaminases and biliary enzymes tended to decrease at 3, 6 and 12 months after the start of MZR treatment; group S also showed a significant decrease in the total bilirubin (TB) level (9.2 mg to 0.9 mg). Moreover, the dosages of steroids and the concentrations of Tac were significantly decreased in all groups, though the dosages of MZR rarely changed throughout the same period. The proportion of patients in each group whose alanine aminotransferase (ALT) and TB levels were within 1.5 times the facility-specific standard increased to 50%, from 0% for ALT, and to 75―100%, from 14.3―66.7% for TB. Adverse effects of MZR treatment were observed in 12 patients (40%), including 5 for whom withdrawal of MZR became necessary because of its adverse effects.
【Conclusion】MZR is a drug that can be used for patients with severe and treatment-resistant rejection, accompanied by steroid-and Tac-sparing effects. Its adverse effects are relatively mild.

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【Objective】There may be a discrepancy in the results between the complement-dependent cytotoxic crossmatch test (CDC-XM) and the flow cytometry crossmatch test (FCXM) for the detection of HLA antibodies (HLA-Abs). We investigated the cause of this discrepancy using the solid-phase assay method with the LABScreen single antigen (LABScreen) and the LABScreen single C1q (C1qScreen).
【Methods】Twenty-one candidates for renal transplantation who visited our outpatient clinic in 2011 were HLA-Abs positive by FlowPRA. Their serums underwent the LABScreen test and the C1qScreen test. The specificity of the Abs in these serums was determined using LABScreen and lymphocyte cells (LCCs) of a third party that had the same antigen as the specified Abs that were selected. Then these LCCs underwent FCXM and CDC-XM. The results of the tests were compared with each other. Moreover, we studied the clinical outcomes of 9 recipients that had tested positive by FCXM and negative by CDC-XM preoperatively. We also studied 3 cases as references of poor graft that had tested negative by FCXM and CDC-XM and developed rejection.
【Results】HLA-Abs that were positive by FCXM using LCCs exhibited 26 kinds of classⅠ and Ⅱ antibodies, and the results of C1qScreen and CDC-XM showed significant correlation with them（p＜0.001）. Those of C1qScreen and LABScreen, however, showed no significant correlation. In 12 recipients who were all CDC-XM negative before transplantation, 9 became LABScreen positive; postoperatively, 4 recipients became C1qScreen positive. Graft loss and C1qScreen of chronic-AMR cases were all positive after transplantation.
【Conclusion】C1qScreen was not always positive, even when FCXM was positive and LABScreen detected a high quantity of HLA-Abs, but C1qScreen was almost always positive when CDC-XM was. That indicates that discrepancy in the results of CDC-XM and FCXM was caused to some extent by the dependency of HLA-Abs on complement. Furthermore, C1qScreen showed positive results in all chronic AMR and graft loss cases, suggesting that complement-dependent donor specific antibodies were partially involved in chronic-AMR and graft loss.

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【Objective】The purpose of this study was to evaluate pharmacokinetic (Pk) profile of newly developed modified release tacrolimus (MR-TAC) in pediatric kidney transplant recipients.
【Methods】According to our current immunosuppressive protocol, tacrolimus (TAC) was initially given and converted to MR-TAC in 13 pediatric patients who received kidney transplantation from April 2010 to April 2011. The switch dose ratio was 1:1, and the 24hour full Pk study was assessed before and after the conversion from TAC to MR-TAC.
【Results】The mean total daily dose at baseline upon enrollment was 5.4±3.3 mg. There was no significant correlation between the oral dose and the trough concentration (C0) of TAC/MR-TAC. The consecutive Pk studies revealed no significant difference in the mean time to maximum concentration (Tmax) / maximum concentration (Cmax) and the area under the time-concentration curve (AUC_0-24) of both reagents; the mean C0 of MR-TAC was 18% lower than those of TAC. A better correlation between AUC_0-24 and C0 was observed in MR-TAC compared to that in TAC (r²＝0.912, for MR-TAC; r²＞0.555, for TAC).
【Conclusion】In the conversion from TAC to MR-TAC, AUC_0-24 was equivalent despite the 18% reduction of C0, even in the pediatric kidney transplant recipients. The trough concentration might be an excellent predictor in the therapeutic drug monitoring of MR-TAC because of its better correlation of C0 and AUC_0-24.

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An indocyanine green (ICG) test is a reliable and convenient examination that has been generally used for evaluating the liver function for hepatectomy, especially in patients with hepatic cirrhosis. We routinely perform an ICG test a preoperative examination for the donor of the living donor liver transplantation (LDLT). Here we report a rare case of living donor with Gilbert's syndrome and a constitutional ICG excretory defect.A 32-year-old woman became a donor candidate of LDLT for her 7-month-old nephew with fulminant hepatic failure. Preoperative examination tests showed no abnormal values except a marked delay of ICG retention rate at 15 minutes (69.2%) and hyperbilirubinemia; total bilirubin was 2.5 mg/dl, and indirect bilirubin was 2.3 mg/dl. The patient was diagnosed as Gilbert's syndrome with constitutional ICG excretory defect but was still entitled as an appropriate living donor. Left lateral segmentectomy was performed for the donor, and there were neither perioperative nor postoperative complications. Laboratory tests of the donor showed no remarkable change during a two-year course after surgery. The recipient was discharged 87 days after the transplantation without severe complications.This case report showed that left lateral segmentectomy could safely be performed on the living donor with Gilbert's syndrome and constitutional ICG excretory defect. However, more data collections and deliberations are required to decide whether a volume extraction of grafts, i.e., right or left lobe, is applicable to this donor.

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A 43-year-old Japanese male developed type I acute aortic dissection and hepatic failure seven months after cadaveric renal transplant. After an urgent hemi-arch replacement, a cerebral infarction, hepatic failure, and left hemiplegia occurred. Because of the sepsis and hepatic failure, all immunosuppressive agents except for the steroids needed to be withdrawn. One month later, as his physical condition improved, his urine output gradually increased, and a renal graft biopsy was performed to evaluate the graft viability. The pathological findings showed no severe rejection, but there was acute tubular necrosis (ATN), mainly a result of renal circulation insufficiency. Low-dose immunosuppressant treatment was resumed, thus resulting in preservation of the renal graft function.

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