Akinari Fukuda

B‐cell surface marker analysis for improvement of rituximab prophylaxis in ABO‐incompatible adult living donor liver transplantation

Although the effectiveness of rituximab has been reported in ABO blood group (ABO)‐incompatible (ABO‐I) organ transplantation, the protocol is not yet established. We studied the impact of the timing of rituximab prophylaxis and the humoral immune response of patients undergoing ABO‐I living donor liver transplantation (LDLT), focusing on clinicopathological findings and the B‐cell subset. From July 2003 to December 2005, 30 adult patients were treated with hepatic artery infusion (HAI) protocol without splenectomy for ABO‐I LDLT. A total of 17 patients were treated only with HAI (no prophylaxis), and the other 13 were treated with rituximab prophylaxis at various times prior to transplantation. For B‐cell study of the spleen, another 4 patients undergoing ABO‐I LDLT both with HAI after prophylaxis and eventual splenectomy, and 3 patients with ABO‐compatible LDLT with splenectomy were enrolled. The mortality of the 30 patients with HAI, without splenectomy, and with/without rituximab prophylaxis was 33% and the main cause of death was sepsis. Peripheral blood B cells were completely depleted, anti‐donor blood‐type antibody titer was lower, and clinical and pathological antibody‐mediated rejection was not observed in patients with prophylaxis earlier than 7 days before transplantation (early prophylaxis). Early rituximab prophylaxis significantly depleted B cells and memory B cells in the spleen but not in lymph nodes. On the other hand, B cells and memory B cells increased and memory B cells became dominant during antibody‐mediated rejection. In conclusion, early prophylaxis with rituximab depletes B cells, including memory B cells, in the spleen and is associated with a trend toward lower humoral rejection rates and lower peak immunoglobulin (Ig)G titers in ABO‐I LDLT patients. Liver Transpl 13:579–588, 2007.

Living donor liver transplantation with hyperreduced left lateral segments.

Liver transplantation is now an established technique to treat children with end-stage liver disease. Implantation of left lateral segment grafts (Couidauds segments II and III) can be a problem in small infants because of a large-for-size graft. Reduced left lateral segmental liver transplantation has been recently introduced for small infants to mitigate the problem of large-for-size graft. Further reduction of the left lateral segment graft increases the possibility of supplying an adequate hyperreduced left lateral segment graft as an alternative surgical technique. We report 3 cases of our experience of transplantation using hyperreduced left lateral segment grafts from living donors.

Efficacy of living donor liver transplantation for patients with methylmalonic acidemia

Application of liver transplantation to methylmalonic acidemia (MMAemia) is controversial because MMAemia is caused by a systemic defect of methylmalonyl‐CoA mutase. The clinical courses of seven pediatric patients with MMAemia undergoing living donor liver transplantation (LDLT) were reviewed. Serum and urinary methylmalonic acid (MMA) levels were found to be significantly decreased after LDLT, whereas serum and urinary MMA levels did not return to normal in any patient. One patient died of sepsis 44 days after LDLT. The other six patients are currently doing well. All patients had preoperative history of acute metabolic decompensation and/or metabolic stroke. However, no episode of acute metabolic decompensation or metabolic stroke was observed postoperatively in any surviving patients. In the preoperative period, all patients showed lethargy and cognitive deficit, both of which were eradicated after LDLT in all surviving patients. Preoperatively, all patients were subjected to dietary protein intake restriction and tube feeding, and were administered several metabolism‐correcting medications. The metabolism‐correcting medications being administered remained mostly unchanged after LDLT, whereas protein restriction was liberalized and tube feeding became unnecessary in all surviving patients. In addition, physical and neurodevelopmental growth delay remained in all surviving patients during the observation period, which ranged from 4 to 21 months with a median of 10.5 months.

Biliary reconstruction in pediatric live donor liver transplantation: Duct-to-duct or Roux-en-Y hepaticojejunostomy

BACKGROUND Duct-to-duct biliary reconstruction (DD) is currently a standard procedure in adult live donor liver transplantation (LDLT). Its pediatric feasibility, however, has rarely been reported. The goal of this study is to assess the incidence and treatment of biliary complication after pediatric LDLT with DD or Roux-en-Y hepaticojejunostomy (RY). METHOD Sixty children received LDLT between November 2005 and June 2008, and their database was reviewed. RESULTS Biliary reconstruction was achieved with DD in 14 patients and with RY in 46 patients with mean follow-up period of 26.0 and 22.3 months, respectively. The incidence of biliary leakage in the DD and RY groups was 7.1% and 8.7%, respectively, and that of stricture was 28.6% and 10.9%, respectively; but the differences were not statistically significant. Biliary stricture in the DD group tended to require revision surgery with RY and longer treatment with percutaneous transhepatic cholangiodrainage compared with that in the RY group. CONCLUSION Theoretical advantages of DD over RY were not confirmed in this study. Duct-to-duct biliary reconstruction tended to encounter more biliary complications, especially stricture, with more difficulty in treating it than RY. Roux-en-Y hepaticojejunostomy seems preferable to DD in the setting of pediatric LDLT, but DD must be considered when making new Roux-en-Y limb seems impossible or troublesome owing to abdominal dense adhesion or short bowel syndrome.

Reducing the thickness of left lateral segment grafts in neonatal living donor liver transplantation

Liver transplantation is now an established treatment for children with end‐stage liver disease. Left lateral segment (LLS) grafts are most commonly used in split and living donor liver transplantation in children. In very small children, LLS grafts can be too large, and further nonanatomical reduction has recently been introduced to mitigate the problem of large‐for‐size grafts. However, the implantation of LLS grafts can be a problem in infants and very small children because of the thickness of the grafts, and these techniques do not address problems related to thickness. We herein describe a technique for reducing the thickness of living donor left lateral grafts and successful transplantation in a 2.8‐kg infant with acute liver failure. Liver Transpl 19:226–228, 2013.

Living donor liver transplantation for glycogen storage disease type Ib

Glycogen storage disease type 1b (GSD‐1b) is due to an autosomal recessive inborn error of carbohydrate metabolism caused by defects in glucose‐6‐phosphatase translocase. Patients with GSD‐1b have severe hypoglycemia with several clinical manifestations of hepatomegaly, obesity, a doll‐like face, and neutropenia. Liver transplantation has been indicated for severe glucose intolerance. This study retrospectively reviewed 4 children with a diagnosis of GSD‐1b who underwent living‐donor liver transplantation (LDLT). Between November 2005 and June 2008, 96 children underwent LDLT with overall patient and graft survival of 92.3%. Of these, 4 (4.2%) were indicated for GSD‐1b. All patients are doing well with an excellent quality of life because of the stabilization of glucose intolerance, decreased hospital admission, and normalized neutrophil count. LDLT appears to be a feasible option and is associated with a better quality of life for patients with GSD‐1b. Long‐term observation may be necessary to collect sufficient data to confirm the efficacy of this treatment modality. Liver Transpl 15:1867–1871, 2009.

The classification based on intrahepatic portal system for congenital portosystemic shunts

BACKGROUND/PURPOSE Liver transplantation was previously indicated as a curative operation for congenital absence of portal vein. Recent advances in radiological interventional techniques can precisely visualize the architecture of the intrahepatic portal system (IHPS). Therefore, the therapeutic approach for congenital portosystemic shunt (CPS) needs to be reevaluated from a viewpoint of radiological appearances. The aim of this study was to propose the IHPS classification which could explain the pathophysiological characteristics and play a complementary role of a therapeutic approach and management for CPS. METHODS Nineteen patients with CPS were retrospectively reviewed. The median age at diagnosis was 6.8 years old. Eighteen of these patients underwent angiography with a shunt occlusion test and were classified based of the severity of the hypoplasia of IHPS. RESULTS The eighteen cases who could undergo the shunt occlusion test were classified into mild (n=7), moderate (n=6) and severe types (n=5) according to the IHPS classification. The IHPS classification correlated with the portal venous pressure under shunt occlusion, the histopathological findings, postoperative portal venous flow and liver regeneration. Shunt closure resulted in dramatic improvement in the laboratory data and subclinical encephalopathy. Two patients with the severe type suffered from sepsis associated with portal hypertension after treatment, and from the portal flow steal phenomenon because of the development of unexpected collateral vessels. The patients with the severe type had a high risk of postoperative complications after shunt closure in one step, even if the PVP was relatively low during the shunt occlusion test. CONCLUSION The IHPS could be visualized by the shunt occlusion test. The IHPS classification reflected the clinicopathological features of CPS, and was useful to determine the therapeutic approach and management for CPS.

Impact of Rewarming Preservation by Continuous Machine Perfusion: Improved Post-Transplant Recovery in Pigs

BACKGROUND Utilization of grafts from donors after cardiac death (DCD) greatly expands the organ pool. However, implementation of such a strategy requires the development of novel preservation methods to achieve recovery from changes owing to warm ischemia. METHODS To assess potential methods, porcine livers harvested after 60 minutes of warm ischemic time (WIT) were perfused and preserved under the following conditions: Group 1 (n = 3), 2-hour simple cold storage and 2-hour machine perfusion (MP) at 8°C; group 2 (n = 3), 2 hours at 25°C and MP at 25°C and group 3 (n = 3), 2-hour simple cold storage and gradual rewarming to 25°C by MP. The preserved liver grafts were transplanted orthotopically into recipients. RESULTS The aspartate aminotransferase (AST), lactate dehydrogenase (LDH), and hyaluronic acid (HA) levels in recipient blood at 2 hours after reperfusion were significantly lower among group 3: AST, 789 ± 258.8, 1203 ± 217.0, and 421 ± 55.8 IU/L; LDH, 1417 ± 671.2, 2132 ± 483.9, and 634 ± 263.9 IU/L; and HA, 1660 ± 556.5, 1463 ± 332.3, and 575 ± 239.0 ng/mL for groups 1, 2 and 3, respectively. Histologically, necrosis and swelling of hepatocytes were less severe among group 3 than groups 1 and 2. Group 3 animals showed better vital responses and started spontaneous breathing within 2 hours after reperfusion; 1 recipient survived for >24 hours, although all animals in groups 1 and 2 died within 2 to 3 hours after reperfusion. CONCLUSION Rewarming by MP preservation may facilitate recovery and resuscitation of DCD liver grafts.

Living‐donor liver transplantation for propionic acidemia

Kasahara M, Sakamoto S, Kanazawa H, Karaki C, Kakiuchi T, Shigeta T, Fukuda A, Kosaki R, Nakazawa A, Ishige M, Nagao M, Shigematsu Y, Yorifuji T, Naiki Y, Horikawa R. Living‐donor liver transplantation for propionic acidemia.

Technical considerations of living donor hepatectomy of segment 2 grafts for infants

BACKGROUND The selection of an adequate graft to mitigate the problems associated with a large-for-size graft is essential to ensure the success of liver transplantation for smaller children. Reduced left lateral segment (LLS) grafts have been introduced to overcome this issue. METHODS Five infants underwent living donor liver transplantation (LDLT) with segment 2 grafts. In the preoperative assessment, the graft-to-recipient weight ratio (GRWR) and the ratio of the thickness of the donor LLS were used as a reference index for graft size matching, and a 3-dimensional (3D) computer-generated model of the donor liver was used for the analysis of the intrahepatic vasculature. During the donor operation, the relevant portal vein branches feeding to the reduced part of segment 3 were first exposed and divided, and then the parenchymal transection was performed. RESULTS Segment 2 grafts were selected in 3 cases and reduced segment 2 grafts were selected in the other 2 cases. The graft reduction was achieved with 46.6 ± 8.2% of the actual LLS, and thus the GRWR was reduced from 5.33 ± 2.09% to 2.70 ± 0.82%. The actual graft thickness was reduced by approximately half after the graft reduction. Primary abdominal closure was performed in all of the recipients. No surgical complications occurred in any of the donors or recipients. CONCLUSION A segment 2 graft could be a valuable option for graft type selection in LDLT for smaller children. Precise planning using a 3D computer-generated model of the donor liver and meticulous operative procedures are necessary to obtain a viable graft.