S. Uemoto

Living related liver transplantation from heterozygote genetic carriers to children with Wilson's disease.

Abstract: We reviewed the outcome of children undergoing living related liver transplantation (LRLT) for Wilson’s disease (WD), and specifically addressed the potential risk associated with the use of donors who were heterozygous for the Wilson genetic defect. LRLTs were carried out in 11 children with WD, nine of whom presented with fulminant hepatic failure and two with end‐stage hepatic insufficiency. The age of the patients ranged from 6 to 16 yr. Eight patients had hepatic encephalopathy and were plasmapheresed preoperatively. The donors (all parents: six fathers and five mothers) were all one‐haplotype matched with their respective recipients, and were all therefore heterozygote carriers of the WD genetic defect. The serum ceruloplasmin levels were within normal limits in all donors (mean: 20.0 ± 2.85 mg/dL). All recipients but one had low serum ceruloplasmin levels with a mean value of 11.6 ± 7.36 mg/dL before transplantation. The serum ceruloplasmin levels had increased to an average of 21. 0 ± 3.76 mg/dL after LRLT at the latest evaluation, which ranged between 7 and 75 months after transplantation. A marked reduction in urinary copper excretion was observed in all recipients after transplantation. Of eight recipients presenting preoperatively with Kayser‐Fleischer (K‐F) rings, this abnormality resolved completely after LRLT in five patients and partially in three. All recipients are alive and remain well, and none have developed signs of recurrent WD after a mean follow‐up period of 31 months (range 7–75 months). In conclusion, LRLT is an excellent choice for effective treatment of WD, and grafts chosen from heterozygote carriers of the condition do not appear to confer any risk of recurrence in the recipients.

Hepatic venous outflow obstruction in pediatric living donor liver transplantation using left‐sided lobe grafts: Kyoto university experience

The goals of this study were to evaluate the incidence of hepatic venous outflow obstruction (HVOO) in pediatric patients after living donor liver transplantation (LDLT) using left‐sided lobe grafts and to assess the therapeutic modalities used for the treatment of this complication at a single center. Four hundred thirteen primary LDLT procedures were performed with left‐sided lobe grafts between 1996 and 2006. All transplants identified with HVOO from a cohort of 380 grafts with survival greater than 90 days were evaluated with respect to the patient demographics, therapeutic intervention, recurrence, and outcome. Seventeen cases (4.5%) were identified with HVOO. Eight patients experienced recurrence after the initial balloon venoplasty. Two patients finally required stent placement after they experienced recurrence shortly after the initial balloon venoplasty. A univariate analysis revealed that a smaller recipient‐to‐donor body weight ratio and the use of reduced grafts were statistically significant risk factors. The cases with grafts with multiple hepatic veins had a higher incidence of HVOO. In conclusion, the necessity of repeated balloon venoplasty and stent placement was related to poor graft survival. Therefore, the prevention of HVOO should be a high priority in LDLT. When grafts with multiple hepatic veins and/or significant donor‐recipient size mismatching are encountered, the use of a patch graft is recommended. Stent placement should be carefully considered because of the absence of data on the long‐term patency of stents and stent‐related complications. New stenting devices, such as drug‐eluting and biodegradable stents, may be promising for the management of HVOO. Liver Transpl 16:1207–1214, 2010.

Decreased ADAMTS13 Levels in Patients after Living Donor Liver Transplantation

INTRODUCTION Thrombotic microangiopathy (TMA) is a complication occurring after liver transplantation (LT), and an unusually large multimer (ULM) of Von Willebrand factor (VWF) and ADAMTS13 may play an important role in the onset of TMA during LT. MATERIAL AND METHODS Eight-one patients underwent living donor LT (LDLT). Seventeen of those patients had both severe thrombocytopenia and hemolytic anemia with fragmented red cells and were diagnosed as TMA- like syndrome (TMALS). RESULTS AND CONCLUSIONS A significant reduction of ADAMTS13 and an increase of VWF were observed in the patients with TMALS. The ADAMTS13 activity in patients after LDLT was significantly reduced from day 1 to day 21, and it was significantly low in those with TMALS at day 14 and 28. The VWF levels in patients with LDLT were significantly high, and the VWF/ADAMTS13 ratio was significantly increased in patients at 7, 14 and 28 days after LDLT, especially in patients with TMALS at day 14 and 28 after LDLT. High molecular weight multimers of VWF were observed to have increased in patients with LDLT, and the high molecular weight multimers of VWF were further increased in those with mild TMALS but they decreased in those with severe TMA. These findings suggest that ULM- VWF and ADAMTS13 might be associated with the onset of TMA after LT.

Selective portal blood flow diversion in auxiliary partial orthotopic liver transplantation to induce regeneration of the graft

Experience with auxiliary partial orthotopic liver transplantation (APOLT) is still very limited and many questions remain to be solved. In this article, we present the case of a 5-year-old girl with ornithine transcarbamylase deficiency who initially did well after APOLT. During a severe rejection episode 16 months after transplantation, she developed encephalopathy and hyperammonemia. Despite a good clinical and histopathological response to antirejection therapy, the graft had become smaller and the native liver had undergone compensatory hypertrophy. After we surgically ligated the right portal branch, the graft recovered and the patient was able to stop her medication 1 month after surgery. We have estimated that the minimum volume of normal liver required to correct the metabolic defect in ornithine transcarbamylase deficiency is 8 cm3/kg. The ligation of the right portal branch was a safe and effective method of inducing a gradual and progressive involution of the hypertrophic native liver and regeneration of the atrophic graft.

Significance of semiquantitative assessment of preformed donor-specific antibody using luminex single bead assay in living related liver transplantation.

Aim. To analyze the risks of preoperatively produced donor-specific antibody (DSA) in liver transplantation. Methods. DSA was assessed using direct complement-dependent cytotoxicity (CDC) and anti-human globulin- (AHG-) CDC tests, as well as the Luminex Single Antigen assay. Among 616 patients undergoing blood type identical or compatible living donor liver transplantation (LDLT), 21 patients were positive for CDC or AHG-CDC tests, and the preserved serum from 18 patients was examined to determine targeted Class I and II antigens. The relationships between the mean fluorescence intensity (MFI) of DSA and the clinical outcomes were analyzed. Results. Patients were divided into 3 groups according to the MFI of anti-Class I DSA: high (11 patients with MFI > 10,000), low (2 patients with MFI < 10,000), and negative (5 patients) MFI groups. Six of 11 patients with high Class-I DSA showed positive Class-II DSA. Hospital death occurred in 7 patients of the high MFI group. High MFI was a significant risk factor for mortality (P = 0.0155). Univariate analysis showed a significant correlation between MFI strength and C4d deposition (P = 0.0498). Conclusions. HLA Class I DSA with MFI > 10,000 had a significant negative effect on the clinical outcome of patients with preformed DSA in LDLT.

Small bowel transplantation using grafts from living-related donors. Two case reports

Abstract A living‐related small bowel transplantation (SBT) was performed in two pediatric patients with short bowel syndrome. In both cases, the donor was the patients mother. The distal ileum (100 cm, 120 cm) was harvested and the ileocolic vessels, ileocecal valve, and terminal ileum were left intact. The two donors were discharged from the hospital on postoperative days 15 and 6, respectively. Recipient 1 was a 2 year 6 month‐old boy with short bowel syndrome who underwent SBT due to loss of venous access. The graft vein was anastomosed to the recipients infrarenal inferior vena cava. Despite triple immunosuppression (tacrolimus, steroid, and azathioprine), there were four episodes of rejection. The patient had been on total parenteral nutrition for almost his entire post‐transplant course. He died from Pneumocystis carinii pneumonia 16 months after the transplantation. Recipient 2 was a 4 year 5 month‐old girl with short bowel syndrome who underwent an isolated small bowel transplantation because of recurrent line sepsis. Her pretransplant bilirubin was 8.0 mg/dl and a biopsy showed severe fibrosis. The graft vein was anastomosed to the recipients inferior mesenteric vein. After transplantation, her bilirubin level became normal within 10 days. Triple immunosuppression (tacrolimus, steroid, and cyclophosphamide) together with a 3‐day course of OKT‐3 made her post‐transplant course feasible. After overcoming a single episode of rejection she left the hospital 4 months after SBT. The patient is currently (10 months after transplantation) hospitalized due to rejection, which is being successfully controlled, and she is off total parenteral nutrition. From our experience, harvesting of the distal ileum for use as a bowel graft can be safely performed. The advantages of living‐related grafts, optimal graft length, and choice of vascular reconstruction in SBT are yet to be explored.

Extension of the indication for living related liver transplantation from children to adults based on resolution of graft size mismatch in relation to tissue oxygenation and metabolic load: a case report

Abstract  We extended the indication for living related partial liver transplantation from pediatric to adult cases. Our first case was a 49‐year‐old woman with primary biliary cirrhosis. Her sisters left lobe, weighing 280 g, was employed as a graft, and the graft weight/recipients body weight ratio was calculated as 0.59 %. To decrease the metabolic load to the relatively small graft, the total bilirubin was decreased from a maximum value of 75.0 mg/dl to the most recent preop‐erative value of 36.2 mg/dl by plasma exchange. Intraoperative recovery of tissue oxygenation and its heterogeneity were satisfactory due to a relatively high blood supply. A postoperative decrease in bilirubin and increase in cholesterol esterifi‐cation were facilitated, concomitant with regeneration of the graft, which weighed 280 g, to 860 c at 3 weeks. Linear regression analysis with respect to tissue oxygenation and metabolic capacity obtained in pediatric cases were applied to this adult case.

The effectiveness of measuring for fragmented red cells using an automated hematology analyzer in patients with thrombotic microangiopathy.

Thrombotic microangiopathy (TMA) or thrombotic thrombocytopenic purpura (TTP) is a life-threatening syndrome characterized by increased number of fragmented red cells (FRCs) and thrombocytopenia. FRCs can be measured using the recently developed automated hematology analyzer XE-2100. The normal range for FRCs is 0% to 0.205%, as determined by the automated hematology analyzer XE-2100. The FRC count is significantly elevated in patients with TMA associated with liver transplantation, bone marrow transplantation, or TTP. In patients with TMA after liver transplantation, the FRC count is significantly higher than in those without TMA. In receiver operating characteristic analysis for the diagnosis of TMA, the area under the curve is 0.986, suggesting that FRC is a useful marker for the diagnosis of TMA. When the cutoff value of FRC for TMA is 1.2%, the sensitivity is 90% and the specificity is 96%, indicating that FRC is the most useful screening test for the diagnosis of TMA.

Incidence and risk factors for herpes zoster in patients undergoing liver transplantation

Herpes zoster (HZ) is the most common manifestation of latent varicella zoster virus reactivation, which occurs naturally as a result of aging or in immunocompromised patients. Solid organ transplant recipients are at increased risk for HZ owing to their chronic immunosuppression. Although several reports investigated risk factors for the development of HZ in heart or renal transplantation, data in liver transplantation (LT) are limited.

Establishment of practical recellularized liver graft for blood perfusion using primary rat hepatocytes and liver sinusoidal endothelial cells

Tissue decellularization produces a three‐dimensional scaffold that can be used to fabricate functional liver grafts following recellularization. Inappropriate cell distribution and clotting during blood perfusion hinder the practical use of recellularized livers. Here we aimed to establish a seeding method for the optimal distribution of parenchymal and endothelial cells, and to evaluate the effect of liver sinusoidal endothelial cells (LSECs) in the decellularized liver. Primary rat hepatocytes and LSECs were seeded into decellularized whole‐liver scaffolds via the biliary duct and portal vein, respectively. Biliary duct seeding provided appropriate hepatocyte distribution into the parenchymal space, and portal vein–seeded LSECs simultaneously lined the portal lumen, thereby maintaining function and morphology. Hepatocytes co‐seeded with LSECs retained their function compared with those seeded alone. Platelet deposition was significantly decreased and hepatocyte viability was maintained in the co‐seeded group after extracorporeal blood perfusion. In conclusion, our seeding method provided optimal cell distribution into the parenchyma and vasculature according to the three‐dimensional structure of the decellularized liver. LSECs maintained hepatic function, and supported hepatocyte viability under blood perfusion in the engineered liver graft owing to their antithrombogenicity. This recellularization procedure could help produce practical liver grafts with blood perfusion.