Tohru Iwahori

Increased sensitivities of peripheral blood mononuclear cells to immunosuppressive drugs in cirrhosis patients awaiting liver transplantation.

Successful immunosuppressive therapy is critical for liver transplantation. However, a considerable number of patients show clinical resistance to the therapy and experience rejection episodes, or alternatively exhibits serious adverse effects of drugs. We examined the in vitro response of peripheral blood mononuclear cells (PBMCs) to immunosuppressive drugs in cirrhosis patients awaiting liver transplantation. We evaluated the suppressive efficacy of prednisolone, methylprednisolone, cyclosporine, and tacrolimus on the in vitro blastogenesis of PBMCs obtained from 22 cirrhosis patients and 31 healthy subjects. In vitro drug concentrations giving 50% inhibition of PBMC blastogenesis (IC50s) were calculated. Two out of these 22 patients received liver transplantation from living donors, and their clinical courses were surveyed until 5 weeks after operation. The median IC50 values for prednisolone, cyclosporine, and tacrolimus against blastogenesis of PBMCs from cirrhosis patients were significantly lower than those of PBMCs from healthy subjects (p < 0.01). However, large individual differences were observed in the IC50 values of the immunosuppressive drugs examined, especially in the cirrhosis patients. One recipient exhibiting high PBMC sensitivity to tacrolimus (IC50 = 0.001 ng/ml) showed good clinical course without rejection until 5 weeks after liver transplantation. The other recipient exhibiting relatively low PBMC sensitivity to taclolimus (IC50 = 0.30) showed allograft rejection at 1 week after operation. We concluded from these observations that PBMCs of cirrhosis patients are vulnerable to the immunosuppressive effects of prednisolone and calcineurin inhibitors. However, large individual variations in the IC50 values suggest that patients exhibiting relatively lower sensitivity to these drugs may have risks of rejection, whereas highly sensitive patients are possibly able to reduce the dose of immunosuppressive drugs to avoid serious drug-adverse effects, after liver transplantation.

How Can We Increase Living Related Donor Renal Transplantations

BACKGROUND In Japan, living donor renal transplantation has gained momentum due to an increased number of patients with end-stage renal disease. Living donation not only provides better outcomes, but also the recipients usually need less medications, thereby increasing the quality of life and reducing the potential side effects of immunosuppression. MATERIALS AND METHODS For the past 25 years, our center had performed 140 open donor nephrectomy (OPNx) renal transplantations. Since July 2003, we changed our procurement operation to living hand-assisted laparoscopic donor nephrectomy (HALNx) in 49 cases. Our operative technique consisted of two 12-mm ports placed in the midaxillary line at the superior and inferior levels of the umbilicus. Next, a 5-cm incision was made in the midline periumbilicus and the hand port system fitted through a midline abdominal incision. RESULTS In 49 cases, HALNx was completed successfully; no patient required conversion to laparotomy. The estimated blood loss was 33.0 +/- 43.4 g and no patient required blood transfusion. In comparison, in OPNx the blood loss was 426.5 +/- 247.6 g (P < .001). The mean operative times were 167.4 +/- 39.7 minutes for HALNx and 228.4 +/- 35.7 minutes for OPNx (P < .001). The postoperative hospital stays were 9.1 +/- 3.8 days for HALNx and 13.0 +/- 1.9 days for OPNx (P < .001). For 3 years prior to introduction of HALNx, we had performed only 10 living donor renal transplantations. Since the introduction of HALNx in 2003, the number of living donors has tripled during the following 3 years. CONCLUSIONS Herein we have reported that HALNx was superior in terms of less operative time and blood loss, postoperative pain and recovery, and shorter hospital stay. Overall donor patient satisfaction was also better in the HALNx group. HALNx is a safe procedure that makes kidney donation more appealing to potential live donors and has increased the living donor pool at our center.

Long-term follow-up ABO-incompatible adult living donor liver transplantation in cirrhotic patients.

Abstract:  ABO‐incompatible liver transplantation is usually contraindicated. The presence in the recipient of preformed anti‐A/B antibodies located on endothelial cells raises the risk of antibody‐mediated humoral rejection of the graft. We describe four successful cases of steroid withdrawal in adult patients who had living‐donor liver transplantation from ABO‐incompatible donors. Antirejection therapy included multiple perioperative plasmapheresis, splenectomy, and a triple immunosuppressive regimen with tacrolimus, methylprednisolone (MPSL), and cyclophosphamide or mycophenolate mofetil (MMF). The maintenance dose of immunosuppression did not differ from that of ABO‐identical cases. After transplantation, intrahepatic arterial infusion therapy with prostaglandin E1 (PG E1) was used. As a result, all four patients were able to achieve long‐term graft survival without steroid use. They all have good liver function and are leading normal lifestyles. Our experience with these four patients suggests the feasibility of controlling humoral rejection and other complications in adult ABO‐incompatible living donor liver transplantations with intrahepatic arterial infusion of PGE1, splenectomy, and plasmapheresis with a regular base of immunosuppression protocol to prevent antibody‐mediated humoral rejection.