岡田 憲樹

Background Hepatic artery complications (HAC) are a serious complication in pediatric liver transplant recipients because its incidence is high and it can occasionally lead to graft liver failure. We herein present a retrospective analysis of our 10-year experience with pediatric living donor liver transplantation (LDLT) focusing on the risk factors and treatments for HAC. Methods Between May 2001 and November 2011, 209 LDLTs were performed for 203 pediatric recipients. We performed the multivariate analyses to identify the factors associated with HAC and showed the therapeutic strategy and outcome for HAC. Results The overall incidence of HAC was 7.2%, and the graft survival of recipients with HAC was 73.3%. The multivariate analysis showed that the pediatric end-stage liver disease score (20), post-transplant laparotomy except for HAC treatment and extra-anatomical hepatic artery reconstruction were independent risk factors for HAC (P = 0.020, P = 0.015 and P = 0.002, respectively). Eleven surgical interventions and 13 endovascular interventions were performed for 15 recipients with HAC. The serum aspartate aminotransferase levels pre- and post-treatment for HAC were significantly higher in the surgical group than in the endovascular group (P = 0.016 and P = 0.022, respectively). Conclusions It is important for recipients with risk factors to maintain strict post-transplant management to help prevent HAC and detect it in earlier stages. Endovascular intervention can be a less invasive method for treating HAC than surgical intervention, and can be performed as an early treatment.

AIM: To assessed the clinical significance of protocol liver biopsy (PLB) in pediatric liver transplantation (LT). METHODS: Between July 2008 and August 2012, 89 and 55 PLBs were performed in pediatric patients at two and five years after LT, respectively. We assessed the histopathological findings using the Metavir scoring system, including activity (A) and fibrosis (F), and we identified factors associated with scores of >= A1 and >= F1. Our results clarified the timing and effectiveness of PLB. RESULTS: The incidences of scores of >= A1 and >= F1 were 24.7% and 24.7%, respectively, at two years after LT and 42.3% and 34.5%, respectively, at five years. Independent risk factors in a multivariate analysis of a score of >= A1 at two years included >= 2 h of cold ischemic time, no acute cellular rejection and an alanine amino transaminase (ALT) level of >= 20 IU/L (P = 0.028, P = 0.033 and P = 0.012, respectively); however, no risk factors were identified for a score of >= F1. Furthermore, no independent risk factors associated with scores of >= A1 and >= F1 at five years were identified using multivariate analysis. A ROC curve analysis of ALT at two years for a score of >= A1 demonstrated the recommended cutoff value for diagnosing >= A1 histology to be 20 IU/L. The incidence of scores of >= A2 or >= F2 at two years after LT was 3.4% (three cases), and all patients had an absolute score of >= A2. In contrast to that observed for PLBs at five years after LT, the incidence of scores of >= A2 or >= F2 was 20.0% (11 cases), and all patients had an absolute score of >= F2. In all cases, the dose of immunosuppressants was increased after the PLB, and all ten patients who underwent a follow-up liver biopsy improved to scores of <= A1 or F1. CONCLUSION: PLB at two years after LT is an unnecessary examination, because the serum ALT level reflects portal inflammation. In addition, immunosuppressive therapy should be modulated to maintain the ALT concentration at a level less than 20 IU/L. PLB at five years is an excellent examination for the detection of early reversible graft fibrosis because no serum markers reflect this finding. (C) 2014 Baishideng Publishing Group Inc. All rights reserved.

Some studies have found that gender mismatch between donors and recipients are related to poor graft prognosis after liver transplantation. However, few studies have investigated the impact of gender mismatch on acute cellular rejection (ACR) in pediatric living donor liver transplantation (LDLT). This retrospective study investigated the clinical significance of these factors in ACR after pediatric LDLT. Between November 2001 and February 2012, 114 LDLTs were performed for recipients with biliary atresia (BA) using parental grafts. We performed univariate and multivariate analyses to identify the factors associated with ACR. The donor-recipient classifications included mother donor to daughter recipient (MD; n=43), mother to son (n=18), father to daughter (FD; n=33), and father to son (n=20) groups. The overall incidence rate of ACR in the recipients was 36.8%. Multivariate analysis showed that gender mismatch alone was an independent risk factor for ACR (P=0.012). The FD group had a higher incidence of ACR than the MD group (P=0.002). In LDLT, paternal grafts with gender mismatch were associated with a higher increased incidence of ACR than maternal grafts with gender match. Our findings support the possibility that maternal antigens may have an important clinical impact on graft tolerance in LDLT for patients with BA.

Anastomotic stricture of the choledochojejunostomy is a common complication after living donor liver transplantation. Most anastomotic strictures can be treated by percutaneous transhepatic cholangiodrainage and/or double balloon endoscopy. However, in severe cases and/or in small infants, neither of these is possible. Our new technique, cholangiography accompanied by cholangioscopy, enabled successful guidewire placement and balloon dilatation in cases with severe anastomotic stricture.

The development of late-onset hepatic venous outflow obstruction (LOHVOO) following pediatric living donor liver transplantation (LDLT) can lead to uncontrollable fibrotic damage in liver grafts, even long-term patency of the graft outflow is achieved with appropriate therapeutic modalities. The aim of this study was to verify our hypothesis that some immunological responses, particularly cellular and/or antibody-mediated rejection (AMR), are associated with LOHVOO, which occurs following damage to liver sinusoidal endothelial cells in zone 3 of liver grafts. One hundred and eighty-nine patients underwent LDLT between May 2001 and December 2010 at our institute. Nine patients (4.8%) were identified as having LOHVOO. The preoperative factors, operative factors, and mortality, morbidity, and survival rates were examined and compared between the groups with and without LOHVOO. No statistical differences were observed between the groups with regard to preoperative factors, technical factors, or postoperative complications. However, FlowPRA reactivity was found to be a statistically significant risk factor for LOHVOO (P=0.006). The patients with both class I- and class II-reactive antibodies also had a significant risk of developing LOHVOO (P=0.03) and exhibited significantly higher retransplant rates. In conclusion, although further studies are needed to clarify this phenomenon, the pathophysiological mechanism underlying the development of LOHVOO after LDLT may be explained by immune-mediated responses that facilitate damage in zone 3 of liver grafts.

Fluid collection is common after living donor liver transplantation (LDLT), and can include hematomas, bilomas, abscesses, and seromas. Although accumulated fluid rarely becomes infected and usually remains localized, localized ascites can sometimes be sufficiently extensive to induce vascular complications. This report presents three such cases in pediatric patients that underwent LDLT. A 33-month-old patient showed an increase in the volume of localized ascites around the hepatic vein anastomoses together with low hepatic vein flow on postoperative day (POD) 47. An 82-month-old patient showed an increase in the volume of localized ascites around the portal vein anastomoses together with low portal vein flow on POD 71. A 63-month-old patient showed an increase in the size of a localized abscess around the hepaticojejunostomy with dilatation of all of the intrahepatic bile ducts on POD 20. These cases illustrate the need for awareness of possible vascular or biliary complications due to compressive localized ascites after LDLT.

Abnormalities of liver function tests are frequently documented in patients with Kawasaki disease, but the mechanism responsible for this has not yet been established. Described herein is the case of a 1-year-10-month-old girl who underwent liver transplantation at 11 months of age. Eleven months after transplantation the patient was diagnosed with Kawasaki disease, which was associated with some portal flow reduction, and received i.v. immunoglobulin, after which fever abated with improvement of portal flow to its pre-fever level. Abnormalities of liver function tests in Kawasaki disease patients may occur as a result of inflammation of both the biliary and portal systems. There are no reports on the potential relationship between Kawasaki disease and the portal vein, and accumulation of further data is necessary to better examine this relationship.

Objectives: Treatment for patients with biliary atresia is a Kasai hepatic portoenterostomy; however, the efficacy of repeat Kasai hepatic portoenterostomy is unclear. This study sought to examine the effect of a prior Kasai hepatic portoenterostomy, especially a repeat Kasai hepatic portoenterostomy, on the outcomes of living-donor liver transplant. Materials and Methods: One hundred twenty-six of 170 children that underwent a living-donor liver transplant between May 2001, and March 2010, received a living-donor liver transplant for biliary atresia. These patients were divided into 2 groups according to the number of previous portoenterostomies: 1 (group A, n=100) or 2 or more Kasai hepatic portoenterostomies (group B, n=26). Portoenterostomy was performed twice in 24 patients in group B, 3 times in 1, and 4 times in I. Preoperative, operative factors, mortality, morbidity, and survival rates were examined and compared between groups. Results: The surgical factors such as operative time, blood loss per weight, cold ischemia time, and weight of the native liver were significantly greater in group B than they were in group A. The patient survival rates were comparable in the 2 groups (94.5% in group A and 93.3% in group B), and the difference was not statistically significant. No statistically significant difference was observed between the groups with regard to vascular complications, biliary complications, and other factors including postoperative variables. Bowel perforation requiring surgical repair was more frequent in group B than it was in group A. Conclusions: Repeat Kasai hepatic portoenterostomy might have a negative effect on patients who undergo living-donor liver transplant for biliary atresia patients with potential lethal complications such as bowel perforation. More biliary atresia patients could have a liver transplant, with improved survival and better life expectancy, if they have inadequate biliary drainage after the initial Kasai hepatic portoenterostomy.

Background: Endotoxin (Et) in the portal vein blood is processed by the hepatic reticuloendothelial system. Thus, it is possible that the Et kinetics of the peripheral venous blood may be useful as a biological index that can be used to evaluate liver function. In this study, we measured Et using the endotoxin activity assay in peripheral venous blood during living donor liver transplantation (LDLT), to study its clinical significance. Methods: Subjects were 17 patients who underwent LDLT. In the perioperative peripheral venous blood, was measured Et activity (EA) using the endotoxin activity assay at 1 or 2 d before LT, and then on 1, 5, 7, 14, and 21 postoperative days. Results: Patients with infections had significantly higher EA levels compared with those without complications before LDLT and 14 postoperative days (P = 0.038 and 0.027, respectively). The average EA level of patients with infections and without complications before LT was 0.22 and 0.08, respectively (P = 0.038). Patients with an EA level higher than 0.20 before LDLT had a significantly longer period of hospitalization compared with those without complications (P = 0.038). Conclusions: A preoperative EA level more than 0.20 is a high risk factor for post-transplant infection and a prolonged period of hospitalization. Crown Copyright (c) 2013 Published by Elsevier Inc. All rights reserved.

症例は2歳9ヵ月男児で、胆道閉鎖症に対し1歳1ヵ月時に母親をドナーとする生体肝移植を施行し、免疫抑制療法をtacrolimus(Tac)とmethylprednisolone(MP)で開始した。7ヵ月目に血清ヒアルロン酸、AST、ALTの上昇を認め、免疫性肝障害と判断してmycophenolate mofetilを追加し、MPは中止した。19ヵ月時にうどんを摂取した際に顔面の紅潮を認め、その後蕁麻疹などのアレルギー症状が頻繁に出現するようになった。アーモンドがのったドーナッツの摂食で喘鳴、チアノーゼが出現し、近医でアナフィラキシーショックと診断された。直前の外来血液検査では好酸球数、IgE、Th2ケモカインレセプターが上昇し、移植前陰性であった特異的IgE抗体価がミルク、小麦、大豆などで強い上昇が認められた。Tac中に合併する食物アレルギーを疑い、Tacからciclosporinへ変更した。その結果、上昇していた検査値は低下してアレルギー症状も消失し、3年経過して食物アレルギーはない。

Endotoxin (Et) in the portal vein blood is processed by the hepatic reticuloendothelial system, and therefore, it is possible that the hepatic clearance of Et may become a biological index for liver function. In this study, Et levels of preoperative peripheral and portal vein blood at the time of liver transplantation (LT) were measured in order to study the meaning. The study population comprised 19 patients in whom pediatric living donor LT was performed. In the preoperative peripheral and the portal vein blood at the time of LT, we measured Et activity (EA) by the Et activity assay (EAA) and the Limulus amebocyte lysate (LAL) method. The preoperative peripheral vein blood showed a low EA in all cases. In the EA of the peripheral and the portal vein blood, the latter showed a significantly high level (p = 0.049). With the LAL method, 5.3% (2/38) of patients were positive for Et. The EAA is considered to be superior to the LAL method for the detection of Et, even in low endotoxinemia, and is also capable of elucidating the Et kinetics by accurately reflecting hepatic clearance.

Background Posttransplant portosystemic shunts may result in severe fatty changes, portal vein complications, or graft liver failure because they reduce the effectiveness of portal perfusion through a portal steal phenomenon. However, the indications and timing of surgical and interventional treatments for posttransplant portosystemic shunts are still a matter of debate. We performed a retrospective investigation of the present state of long-term outpatients with posttransplant portosystemic shunts. Methods This study comprised 150 outpatients who underwent liver transplantation between October 1988 and August 2006 in our department and other facilities. The diagnosis was based on the presence of any portosystemic shunts with the diameter of more than 5 mm indicated by computed tomography. Results A total of 16 patients (16/150, 10.7 %) were diagnosed as having posttransplant portosystemic shunt. Among them, eight patients (8/16, 50.0 %) developed portal vein complications, and 1 (1/16, 6.3 %) developed graft liver failure. Conclusions The persistence of posttransplant portosystemic shunts results in portal vein complications or graft liver failure. Therefore, surgical and interventional treatment for patients with posttransplant portosystemic shunts should be performed based on the clinical and radiologic findings.

The pediatric end-stage liver disease (PELD) score is not a direct index that reflects the degree of hepatocellular injury. Beta-d glucan (BDG) in the portal vein blood is processed by the hepatic reticuloendothelial system. It is possible that the hepatic clearance of BDG may be used as a biological index to assess the liver function. In this study, the relationship between PELD score and hepatic clearance of BDG was made clear in order to study the efficacy of measurement of the serum BDG. This study including 21 patients with biliary atresia (BA) who underwent liver transplantation (LT) was performed. The BDG was measured in the preoperative peripheral vein blood and the portal vein blood at the time of LT. The portal vein blood showed a significantly high level of BDG than the peripheral vein blood (p < 0.01). There was a significant negative correlation between the PELD score and the hepatic clearance of BDG in the 10 patients who were indicated for LT due to liver failure (p < 0.01). The serum BDG can be used as a biological index in place of liver metabolism and should be measured in BA patients as a non-invasive indicator of the degree of progression of liver failure.

Sanada Y, Urahashi T, Ihara Y, Wakiya T, Okada N, Yamada N, Mizuta K. Liver transplantation for a pediatric patient with hemophilia B. ?Pediatr Transplantation 2012: 00: 000000. (c) 2012 John Wiley & Sons A/S. Abstract: Hemophilia exposes patients to greater risks of bleeding complications during the perioperative period. However, there are no current protocols for factor replacement during LT. We herein describe a case of pediatric living donor LDLT performed for a patient with hemophilia B using perioperative short-term factor replacement. A 4-yr-old female patient with an extrahepatic portosystemic shunt and asymptomatic hemophilia B (factor IX activity 18.7%) underwent an ABO-compatible LDLT using a left lobe graft. The bleeding volume was 2980 mL. Freeze-dried human blood coagulation factor IX concentrate (Novact M, Kaketsuken, Japan) was administered at the induction of anesthesia and at the end of LDLT by bolus infusion (80 U/kg) and was continued by bolus infusion (40 U/kg) on POD 1, 2, 3, and 4. On POD 1, 5, 8, and 12, the factor IX plasma levels were 34.5%, 64.9%, 43.5%, and 53.1%, respectively. The postoperative course was uneventful, and the patient is currently doing well at 2.5 yr after LDLT. Factor concentrate should be administered at the induction of anesthesia and at the end of LT by bolus infusion, and thereafter be continued for a few days after LT by bolus infusion.

実験用ブタを用いた多内臓移植と小腸移植の手術経験について報告した。実験用ブタを用いて異所性自己小腸移植9回と多内臓移植2回を施行した。異所性自己小腸移植と多内臓移植の手術時間は、それぞれ平均300分、334分であった。また、冷阻血時間は、平均53分、116分で、温阻血時間は平均38分、40分であり、バックテーブル時間は、平均29分、17分であった。異所性自己小腸移植におけるグラフト小腸摘出時間は平均90分であった。また、グラフト血管の動脈径、静脈径は平均4.2mm、9.8mmで、吻合時間は平均動脈16分、静脈13分であった。また、多内臓移植におけるグラフト多内臓摘出時間は平均129分であった。吻合時間は平均動脈12分、静脈7分であった。全例で再灌流後30分間、良好な臓器血流が得られた。

9歳男児。日齢76に胆道閉塞症に対し葛西手術を施行した。今回、黄疸の進行で生体肝移植目的に入院となった。45歳の父親をドナーとした拡大左葉グラフトによる生体肝移植を行った。術後早期より肝機能障害を伴わない5000〜10000ml/dayの大量腹水が出現し、肝生検で急性拒絶反応(P3B3V3)を認め、類洞および中心静脈周囲の線維化を伴い、ステロイドパルス療法および腹水濃縮還流を開始した。腹水は改善せず、急性拒絶反応(P1B1V3)は改善したが、中心静脈内皮炎と周囲の線維化が高度で、拒絶反応は遷延していると判断した。肝静脈狭窄を疑い、腹部造影CTおよび経内頸静脈的肝静脈造影を行ったが、肝静脈吻合部の狭窄は認めなかった。3回のステロイド療法でも腹水は減少せず、ステロイド抵抗性拒絶反応と診断し、第62病日よりOKT3の10日間使用により徐々に腹水は減少した。第75病日に急性拒絶反応(P0B0V0)の改善、中心静脈周囲および類洞線維化の改善を確認し、第94病日に腹腔ドレーン抜去となり第108病日に退院した。肝移植後2年を経て経過は良好である。