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Introduction Although hepatic vein stenosis after liver transplantation is a rare complication, the complication rate of 1% to 6% is higher in pediatric living-donor liver transplantation than that in other liver transplantation cases. Diagnosis is very important because this complication can cause hepatic congestion that develops to liver cirrhosis, graft loss, and patient loss. However, this is unlikely in cases where there are no ascites or hypoalbuminemia. Objectives Eleven of 167 patients who had undergone pediatric living-donor liver transplantation were identified in the outpatient clinic at Jichi Medical University as having suffered from hepatic vein stenosis, and were enrolled in the study. Methods We conducted a retrospective study in which we reviewed historical patient records to investigate the parameters for diagnosis and examine treatment methods and outcomes. Results The 11 patients were treated with 16 episodes of balloon dilatation. Three among these received retransplantation and another 2 cases required the placement of a metallic stent at the stenosis. Histological examination revealed severe fibrosis in four of nine patients who had a liver biopsy, with mild fibrosis revealed in the other five grafts. Furthermore, hepatomegaly and splenomegaly diagnosed by computed tomography, elevated levels of hyarulonic acid, and/or a decrease in calcineurin inhibitor clearance were found to be pathognomonic at diagnosis, and tended to improve after treatment. Conclusions Diagnosis of hepatic vein stenosis after liver transplantation can be difficult, so careful observation is crucial to avoid the risk of acute liver dysfunction. Comprehensive assessment using volumetry of the liver and spleen and monitoring of hyarulonic acid levels and/or calcineurin inhibitor clearance, in addition to some form of imaging examination, is important for diagnosis and evaluation of the effectiveness of therapy.

Purpose Cytomegalovirus (CMV) infection is known to be the most frequently viral infection among patients after liver transplantation. This is especially true in pediatric living-donor liver transplantation because the recipients have often not been infected with CMV and postoperative primary infection with CMV frequently occurs. Patients and Methods Of 93 patients who underwent pediatric liver transplantation at our department, 33 patients (36.3%) were diagnosed with CMV infection using the antigenemia method (C7-HRP). Retrospective review and statistical analysis were conducted to confirm risk factors of post-transplantation CMV infection. Result Positive lymphocytes were diagnosed between postoperative days 8 and 111 after transplantation. Ganciclovir or foscavir were administrated to 21 patients. The other 10 patients who had one positive lymphocyte were observed and the cell disappeared on follow-up examination. We did not observe any cases of positive lymphocytes with C7-HRP in patients who received a graft from a CMV antibody−negative donor. Independent predictors associated with CMV infection in the multivariable analysis were administration of OKT3 and grafts from CMV antibody−positive donors. Conclusion In CMV infection after pediatric liver transplantation, cases with CMV antibody−positive donors and with OKT3 administration for acute rejection are considered high risk, and cases with CMV antibody−negative donors are considered low risk.

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.

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

Urahashi T, Mizuta K, Sanada Y, Wakiya T, Yasuda Y, Kawarasaki H. Liver graft volumetric changes after living donor liver transplantation with segment 2 graft for small infants. Abstract: LT for small infants weighing

In the field of pediatric living donor liver transplantation, the indications for apheresis and dialysis, and its efficacy and safety are still a matter of debate. In this study, we performed a retrospective investigation of these aspects, and considered its roles. Between January 2008 and December 2010, 73 living donor liver transplantations were performed in our department. Twenty seven courses of apheresis and dialysis were performed for 19 of those patients (19/73; 26.0%). The indications were ABO incompatible-liver transplantation in 11 courses, fluid management in seven, acute liver failure in three, renal replacement therapy in two, endotoxin removal in two, cytokine removal in one, and liver allograft dysfunction in one. Sixteen courses of apheresis and dialysis were performed prior to liver transplantation for 14 patients. The median IgM antibody titers before and after apheresis for ABO blood type-incompatible liver transplantation was 128 and eight, respectively (P

Background Acute cellular rejection (ACR) is a common cause of morbidity following liver transplantation. Several reports have evaluated the predictive value of peripheral blood eosinophilia as a simple noninvasive diagnostic marker for ACR. This study examined whether the relative eosinophil counts (REC) predicted ACR in pediatric living donor liver transplantation (LDLT). Methods One hundred three patients underwent LDLT between May 2001 and December 2007. ACR were diagnosed based on the pathological findings. Results The incidence of ACR was 46.6% (48/103); ACR was diagnosed an average of 13.5 days after LDLT. The average REC at 4 and 2 days before the onset ACR (n = 39) within 30 postoperative day (POD) was 4.3% and 7.3%, respectively, and 9.0% at the onset. Patients with ACR showed significantly higher levels of REC compared with those free of ACR ( P = .039). REC thresholds of 10% at POD 7 displayed a sensitivity and specificity of ACR detection of 80% and 75%, respectively. Moreover, the accumulated morbidity ratio of ACR within 30 POD was significantly higher with REC >10% at POD 7 ( P = .007). Conclusion ACR within POD 30 should be considered when REC is >10% at POD 7 after LDLT.

Objectives The aim of this study was to evaluate patients who developed varicella zoster virus (VZV) disease after pediatric living donor liver transplantation (PLDLT). Methods Two hundred fifty-five patients who underwent PLDLT between 1995 and 2010 were included in this study. Pretransplantation vaccination of VZV was performed for all recipients except emergency PLDLTs. Posttransplantation VZV vaccination was administered to the patients with a low VZV antibody titer 2 years or more after transplantation. The clinical course and outcomes of VZV disease in cases were reviewed with the transplant database and hospital medical records. Results Sixty-three patients developed VZV disease (chicken pox in 61, herpes zoster in 2) at a median onset of 36 months after PLDLT and at a median age of 4 years old, with a cumulative incidence of 25%. All chicken pox occurred in VZV antibody-negative patients. The onset of herpes zoster in the two patients occurred within 3 months after PLDLT; in addition, these patients were VZV antibody-positive patients. The clinical presentations of most patients were not serious and there were no disseminated infections. Although only 3 patients (5%) were hospitalized, the other 60 patients (95%) all showed a good response to oral antiviral therapy. Conclusions Although VZV disease is an infectious disease with a high morbidity rate after PLDLT, it can normally be successfully managed on an outpatient basis at home. Pre- and posttransplantation vaccinations are effective for delaying the onset of chicken pox after PLDLT and to prevent it from developing into a serious illness.

Background Nonanastomotic biliary stricture is generally considered the most troublesome biliary complication after liver transplant. Nonanastomotic biliary stricture owing to immunologic cholangiopathy (such as acute cellular rejection) has not been reported. We describe 2 patients with the co-occurrence of nonanastomotic biliary stricture and acute cellular rejection after pediatric live-donor liver transplant. CASE 1: A 13-month-old male infant with liver cirrhosis underwent an ABO-identical live-donor liver transplant using a left lateral segment graft. Eighty days after the live-donor liver transplant, ever with liver dysfunction and dilatation of the intrahepatic bile duct occurred. Percutaneous transhepatic biliary drainage and a liver biopsy were performed. The histopathologic evaluation indicated the presence of acute cellular rejection. After percutaneous transhepatic biliary drainage and steroid pulse treatment, the patient showed good clinical outcome. CASE 2: A 21-month-old female infant with biliary atresia underwent an ABO-identical live-donor liver transplant using a left lateral segment graft. Twenty-six days after the live-donor liver transplant, percutaneous transhepatic biliary drainage for B3 and a liver biopsy were performed, owing to fever, with liver dysfunction, and dilatation of the intrahepatic bile duct. Histopathologic evaluation indicated the presence of acute cellular rejection. After percutaneous transhepatic biliary drainage and steroid pulse treatment, the patient showed good clinical outcome. Conclusions It is important for patients with nonanastomotic biliary stricture to undergo early liver biopsy because the nonanastomotic biliary stricture may be coincident with, or caused by, acute cellular rejection.

Liver transplantation for biliary atresia is indicated whenever a Kasai portoenterostomy is considered unfeasible. However, the timing of liver transplantation in biliary atresia has not been precisely defined. Excessive shortening of hepatocellular telomeres may occur in patients with biliary atresia, and therefore, telomere length could be a predictor of hepatocellular reserve capacity. Hepatic tissues were obtained from 20 patients with biliary atresia who underwent LT and 10 age-matched autopsied individuals (mean age, 1.7 and 1.2 years, respectively). Telomere lengths were measured by Southern blotting and quantitative fluorescence in situ hybridization using the normalized telomere-centromere ratio. The correlation between the normalized telomere-centromere ratio for the hepatocytes in biliary atresia and the pediatric end-stage liver disease score was analyzed. The median terminal restriction fragment length of the hepatic tissues in biliary atresia was not significantly different from that of the control (p = 0.425), whereas the median normalized telomere-centromere ratio of hepatocytes in biliary atresia was significantly smaller than that of the control (p

Background Excessive portal pressure at an early stage after living-donor liver transplantation (LDLT) can damage sinusoidal endothelial cells and hepatocytes through shear stress leading to graft failure, or hepatic arterial complications due to low hepatic artery flow from a hepatic arterial buffer response. We encountered a case in which excessive portal vein flow was observed from an early stage after pediatric LDLT. The hepatic artery flow decreased due to a hepatic arterial buffer response. Case report A 6-month-old boy with biliary atresia showed excessive portal vein flow early after LDLT with a decreasing hepatic artery flow without anastomotic stenosis from postoperative day 3. The PV flow gradually exhibited a decrease at approximately postoperative day 8 and, similtaneously, hepatic artery flow exhibited improvement. Conclusion Because excessive portal pressure after LDLT is reversible, it has been suggested that it may be possible to prevent the progress of hepatic arterial complications if temporary portal pressure modulation can be performed for cases among the high-risk group for hepatic arterial complications.

Urahashi T, Mizuta K, Sanada Y, Wakiya T, Umehara M, Hishikawa S, Hyodo M, Sakuma Y, Fujiwara T, Yasuda Y, Kawarasaki H. Pediatric liver retransplantation from living donors can be considered as a therapeutic option for patients with irreversible living donor graft failure. Pediatr Transplantation 2011: 15: 798–803. © 2011 John Wiley & Sons A/S. Abstract: Liver retransplantation (re-LT) is required in patients with irreversible graft failure, but it is a significant issue that remains medically, ethically, and economically controversial, especially in living donor liver transplantation (LDLT). The aim of this study was to evaluate the outcome, morbidity, mortality, safety and prognostic factors to improve the outcome of pediatric living donor liver retransplantation (re-LDLT). Six of 172 children that underwent LDLT between January 2001 and March 2010 received a re-LDLT and one received a second re-LDLT. The overall re-LDLT rate was 3.5%. All candidates had re-LDLT after the initial LDLT. The overall actuarial survival of these patients was 83.3% and 83.3% at one and five yr, respectively. These rates are significantly worse than the rates of pediatric first LDLT. Vascular complications occurred in four patients and were successfully treated by interventional radiologic therapy. There were no post-operative biliary complications. One case expired because of hemophagocytic syndrome after re-LDLT. Although pediatric re-LDLT is medically, ethically, and economically controversial, it is a feasible option and should be offered to children with irreversible graft failure. Further investigations, including multicenter studies, are therefore essential to identify any prognostic factors that may improve the present poor outcome after re-LDLT.

Ornithine transcarbamylase deficiency, the most common urea cycle disorder, causes hyperammonemic encephalopathy and has a poor prognosis. Recently, LT was introduced as a radical OTCD treatment, yielding favorable outcomes. We retrospectively analyzed LT results for OTCD at our facility. Twelve children with OTCD (six boys and six girls) accounted for 7.1% of the 170 children who underwent LDLT at our department between May 2001 and April 2010. Ages at LT ranged from nine months to 11 yr seven months. Post-operative follow-up period was 3-97 months. The post-operative survival rate was 91.7%. One patient died. Two patients who had neurological impairment preoperatively showed no alleviation after LT. All patients other than those who died or failed to show recovery from impairment achieved satisfactory quality-of-life improvement after LT. The outcomes of LDLT as a radical OTCD treatment have been satisfactory. However, neurological impairment associated with hyperammonemia is unlikely to subside even after LT. It is desirable henceforth that more objective and concrete guidelines for OTCD management be established to facilitate LDLT with optimal timing while avoiding the risk of hyperammonemic episodes.

Hepatopulmonary syndrome (HPS) is a progressive, deteriorating complication of end-stage liver disease (ESLD) that occurs in 13-47% of liver transplant candidates. Although LT is the only therapeutic option for HPS, it has a high morbidity and mortality, especially in patients with severe hypoxemia before transplantation, but the course of HPS after living donor liver transplantation (LDLT), especially for biliary atresia (BA) patients is not well established.The present study evaluated 122 patients who received an LDLT for BA and of these, 3 patients had HPS at the time of LDLT in a single-center series.Two patients of the HPS patients them had biliary and/or vascular complications, but they recovered uneventfully with interventional treatment. None of the patients required supplemental oxygen and had no residual cardiopulmonary abnormalities at a follow-up of more than 24 months.Although a series of three patients is too small for definitive conclusion and further investigations must be conducted, pediatric LDLT can be a favorable therapeutic option for HPS.

BACKGROUND At the present time, indications of liver transplantation (LT) for jaundice-free biliary atresia (BA) patients include intractable cholangitis, portal hypertension and pulmonary vascular disorders. However, the timing of LT remains unclear. In the current study, we describe the therapeutic strategies for jaundice-free BA patients. MATERIAL/METHODS 129 BA patients were undergone LDLT between May, 2001 and April, 2010 in the Department of Transplant Surgery, Jichi Medical University, Japan. RESULTS The indications of LDLT for jaundice-free BA patients was 30 patients (30/129, 23%), and included portal hypertension (16 patients, 53%). Among the 16 patients with portal hypertension, there were 7 patients (7/16, 23%) in which uncontrollable gastrointestinal bleeding was an indication of LDLT. There were 5 patients (5/7; 71%) in which bleeding sites were not identified, and 3 patients (3/7; 43%) in which supportive treatments against collateral vessels were performed as a previous treatment. CONCLUSIONS Even in jaundice-free BA patients, after supportive treatments for portal hypertension are performed, it is necessary to assess the esophageal and gastrointestinal varices regularly and to also prepare for LT simultaneously because there is a probability of the complication of uncontrollable gastrointestinal bleeding.

Early hepatic artery complications after liver transplantation in children, having undergone LDLT, can directly affect graft and recipient outcomes, making early diagnosis and treatment essential. In the past, laparotomy (thrombectomy or reanastomosis) was generally employed to treat early hepatic artery complications. Recently, favorable outcomes of IR have been reported. In children, however, the number of such reports is small. To the best of our knowledge, there is no published report on IR applied to neonates with early hepatic artery complications. We recently succeeded in safely using IR for a neonate with early hepatic artery complications after LDLT and obtained a favorable outcome. This case is presented herein.

Wakiya T, Sanada Y, Mizuta K, Umehara M, Urahashi T, Egami S, Hishikawa S, Nakata M, Hakamada K, Yasuda Y, Kawarasaki H. Hepatic artery reconstruction with the jejunal artery of the Roux-en-Y limb in pediatric living donor liver re-transplantation. Abstract: When re-anastomosis and re-transplantation becomes necessary after LDLT, arterial reconstruction can be extremely difficult because of severe inflammation and lack of an adequate artery for reconstruction. Frequently, the recipient’s HA is not in good condition, necessitating an alternative to the HA. In such cases, the recipient’s splenic artery, right gastroepiploic artery or another vessel can be safely used for arterial reconstruction. There have, however, been few reports on using the jejunal artery. Herein, we report our experience with arterial reconstruction using the jejunal artery of the Roux-en-Y limb as an alternative to the HA. A three-yr-old girl who had developed graft failure due to early HA thrombosis after LDLT required re-transplantation. At re-transplantation, an adequate artery for reconstruction was lacking. We reconstructed the artery by using the jejunal artery of the Roux-en-Y limb, as we judged it to be the most appropriate alternative. After surgery, stent was deployed because hepatic blood flow had reduced due to kinking of the anastomosed site, and a favorable outcome was obtained. In conclusion, when an alternative to the HA is required, using the jejunal artery is a feasible alternative.

Bowel perforation after liver transplantation (LT) is a rare, but highly lethal complication with a poor prognosis. Here, we report the outcome of cases of bowel perforation after pediatric LT in our department.The study subjects were 148 patients who underwent pediatric living donor liver transplantation. The 114 with biliary atresia (BA) were divided into two groups: those with associated bowel perforation (Group A) and those without (Group B).Four patients in all (2.5%) suffered bowel perforation. Their original disease was BA and emergency surgery was performed in all cases, with a mortality rate of 50.0%. Comparison of Groups A and B revealed significant differences in the patient age, body weight, duration of surgery, cold ischemic time, and blood loss volume. The survival rates in Groups A and B were 50.0 and 99.1%, respectively (p0.01). Duration of surgery was an independent risk factor (p = 0.05).Bowel perforation after LT is a potentially fatal complication. LT is a procedure that requires care and precision, and the possibility of bowel perforation should always be borne in mind during post-operative management, when the duration of surgery has been long.

Summary Bilioenteric anastomotic stricture after liver transplantation is still frequent and early detection and treatment is important. We established the management using double-balloon enteroscopy (DBE) and evaluated the intractability for bilioenteric anastomotic stricture after pediatric living donor liver transplantation (LDLT). We underwent DBE at Jichi Medical University from May 2003 to July 2009 for 25 patients who developed bilioenteric anastomotic stricture after pediatric LDLT. The patients were divided into two types according to the degree of dilatation of the anastomotic sites before and after interventional radiology (IVR) using DBE. Type I is an anastomotic site macroscopically dilated to five times or more, and Type II is an anastomotic site dilated to less than five times. The rate of DBE reaching the bilioenteric anastomotic sites was 68.0% (17/25), and the success rate of IVR was 88.2% (15/17). There were three cases of Type I and 12 cases of Type II. Type II had a significantly longer cold ischemic time and higher recurrence rate than Type I (P = 0.005 and P = 0.006). In conclusion, DBE is a less invasive and safe treatment method that is capable of reaching the bilioenteric anastomotic site after pediatric LDLT and enables IVR to be performed on strictures, and its treatment outcomes are improving. Type II and long cold ischemic time are risk factors for intractable bilioenteric anastomotic stricture.

Portal vein complications after liver transplantation (LT) are serious complications that can lead to graft liver failure. Although the treatment of interventional radiology (IVR) by means of balloon dilatation for portal vein stenosis (PVS) after LT is an effective method, the high rate of recurrent PVS is an agonizing problem. Anticoagulant therapy for PVS is an important factor for preventing short-term recurrence following IVR, but no established regimen has been reported for the prevention of recurrent PVS following IVR. In our population of 197 pediatric patients who underwent living donor liver transplantation (LDLT), 22 patients (22/197, 11.2%) suffered PVS. In the 9 earliest patients, unfractionated heparin was the only anticoagulant therapy given following IVR. In the 13 more recent patients, 3-agent anticoagulant therapy using low-molecular-weight heparin, warfarin, and aspirin was employed. In the initial group of 9 patients, 5 patients (55.6%) suffered recurrent PVS and required repeat balloon dilatation. Among the 13 more recent patients, none experienced recurrent PVS (P = 0.002). In conclusion, our 3-agent anticoagulant therapy following IVR for PVS in pediatric LDLT can be an effective therapeutic strategy for preventing recurrent PVS.

［背景］ 先天性門脈体循環シャント（Congenital extrahepatic portosystemic shunt：CEPS）は，症候性CEPSにおいて内科的治療抵抗性の場合，外科的治療の適応となる．今回，2例の症候性CEPSに対しシャント血管結紮術を施行し，良好な結果を得たので報告する． ［症例1］ 8才，男児．検診による精査にて肝腫瘍を指摘され，増大傾向を認めたため，静脈管結紮切離術を施行した．術後1年6カ月，CT上多発性肝腫瘍は明らかに縮小した． ［症例2］ 1才4カ月，女児．出生後より腎静脈レベルの下大静脈に直接流入するシャント血管を認めており，肝肺症候群が悪化したため，シャント血管結紮切離術を施行した．術後6カ月で在宅酸素療法を離脱でき，レントゲン上も明らかに改善した． ［考察］ 症候性CEPSに対する外科的治療は，種々の合併症の根治的治療になるため，時期を逸せずに施行すべきである．外科的治療法の選択の際，術前の肝内門脈評価と門脈圧測定が重要である．

A 7-month-old boy with biliary atresia accompanied by situs inversus and absent inferior vena cava (IVC) underwent living-donor liver transplantation (LDLT). Because a constriction in the recipient hepatic vein (HV) was detected during the preparation of the HV in LDLT, a dissection in the cranial direction and a total clamp of the suprahepatic IVC was performed, and the suprahepatic IVC and the graft HV were anastomosed end-to-end. Postoperatively, atelectasis in the left upper lobe and ventilator failure accompanied by an elevation of the left hemidiaphragm were observed and mechanical ventilation was repetitively required. Paralysis in the left phrenic nerve was diagnosed by chest radiograph and ultrasonography. In our patient, conservative treatment was administrated, because weaning him from mechanical ventilation was possible a few days after intubation and the ventilator function was expected to be improved with growth. The disease course was good, and he was discharged from the hospital at 78 days after LDLT. Complications of paralysis in the phrenic nerve after cadaveric liver transplantation have been reported to be high. Although using a conventional technique during the reconstruction of the HV may injure the phrenic nerve directly, use of the piggyback technique with preservation of the IVC is rare. Even if LDLT was undertaken, a dissection of the HV or a total clamp of the suprahepatic IVC as a conventional technique can directly injure the phrenic nerve. Therefore, a dissection of the HV or a total clamp of the suprahepatic IVC at the reconstruction of the HV in LDLT should be carefully performed, and the possibility of paralysis in the phrenic nerve should be considered in patients with a relapse of respiratory symptoms and an elevation of the hemidiaphragm after LDLT.

Background The aim of this study was to determine the existence and extent of maternal microchimerism in the livers of biliary atresia (BA) patients. Methods Two series of investigations were performed based on the sex of our subjects. Subjects for series I were men, of which 6 had BA. Livers were analyzed using X and Y chromosome probes and fluorescent in situ hybridization. Subjects for series II were woman. Nine BA cases and their mothers were HLA typed (class I). Daughter livers were also tested for antibodies to maternal and other HLA. Two cases of neonatal hepatitis, 2 cases of Alagille syndrome, and 1 case of Byler syndrome acted as controls. Results All male BA livers were found to contain a mixture of cells with 1 and 2 X chromosomes (ie, XY or XX). All livers from male controls had only 1 X chromosome (ie, XY). All female BA subjects had varying intensities of antimaternal HLA class I (HLA-A) antibodies in their bile duct epithelium and hepatocytes (strong, 5; mild, 3; weak, 1). The liver from the female control did not display any antimaternal HLA class I antibodies (HLA-Ab). Conclusion Our preliminary data appear to show that maternal microchimerism is present within the livers of patients with progressive postnatal type BA. We suggest that BA could in fact be a graft-vs-host disease masquerading as an autoimmune reaction triggered by maternal microchimerism, and we intend to pursue this hypothesis further to clarify the etiology of BA.

Hypocholinesterasemia is often observed clinically, especially in various liver diseases. Not well known, however, is the fact that some patients have a hereditary BChE variant. Little has been reported on liver transplants associated with this hereditary BChE variant. Furthermore, no cases have been reported of a LDLT involving hereditary BChE variant that had been diagnosed preoperatively. A 23-month-old girl who had had a failed Kasai operation for biliary atresia underwent a liver transplant using as a graft her father's lateral segment. Preoperatively, she had been diagnosed with hypocholinesterasemia. As the donor, her father had undergone a preoperative examination, during which he was found to also have hypocholinesterasemia. DNA sequencing revealed that both had the hereditary BChE variant. The unique mutation caused a frame-shift mutation. Variant K was also detected. The patient was discharged 143 days after the operation and has had no problems with immunosuppression since. In conclusion, we report that the hereditary BChE variant is not a contraindication for either transplantation or living liver donation.

With child living donor liver transplantation (LDLT), two people from one family, a child patient and one parent and one parent are forced to be hospitalized, so the family faces very servere problems. This is especially severe in cases when pediatric patients have siblings. Our research investigated the influence of LDLT upon families with siblings as compared to those without, especially the impact of surgery and hospitalization on family relationships. Families with siblings had more stress about child care and they tended to be more anxious about child development. The siblings had a lot of stress and mental problems. Therefore, the families of LDLT are seen to need special supports, especially those who had siblings.

Acute overdose of tacrolimus appears to cause no or minimal adverse clinical consequences. We encountered a pediatric case who underwent liver transplantation associated with hepatic artery thrombosis (HAT), which recurred following acute tacrolimus overdose. A 10-month-old girl underwent living-related liver transplantation because of biliary atresia. To reconstruct the hepatic artery, the right gastroepiploic artery of the donor was interposed between the right hepatic artery of the recipient (2.5 mm in diameter) and the left hepatic graft artery (1 mm in diameter) under microscopy. On postoperative day 4, Doppler ultrasonography showed a remarkable reduction in hepatic arterial flow, which was consistent with HAT. The patient underwent immediate hepatic arteriography and balloon angioplasty. The stenotic sites were dilated by the procedure. Tacrolimus was infused intravenously after transplantation and the infusion rate was adjusted to achieve a target concentration of 18-22 ng/mL, which remained stable until the morning of day 6. An unexpectedly high blood concentration of tacrolimus (57.4 ng/mL) was detected at 6:00 PM on day 6, and tacrolimus was discontinued at 9:00 PM; however, the tacrolimus level reached 119.5 ng/mL at 0:00 h on day 7. While the concentration decreased to 55.2 ng/mL on the morning of day 7, the hepatic arterial flow could not be observed by Doppler ultrasonography. Emergent hepatic arteriography showed stenosis of the artery at the proximal site of the anastomosis. Balloon angioplasty was again performed and the stenotic site was successfully dilated. High level of tacrolimus exposure to the hepatic artery with injured endothelium by preceding angioplasty may have been related to the recurrence of HAT in the present case.

We encountered two cases of pediatric living-related liver transplant recipients who showed increases in blood concentration of cyclosporine or tacrolimus, a dual substrate for cytochrome P450 (CYP) 3A and P-glycoprotein (P-gp), during a diarrheal episode. To investigate the effect of intestinal inflammation on the metabolic and efflux pump activities, we conducted the experiments using the lipopolysaccharide (LPS)-induced intestinal damage model. Intestinal epithelial CYP3A activity was assessed by nifedipine oxidation using intestinal epithelial microsomes in rat. Drug efflux by P-gp was tested using digoxin flux with the excised intestine perfusion system in rats. Intraperitoneal injection of LPS (0.3 mg/kg) significantly reduced the intestinal epithelial CYP3A activity by 41% (p < 0.01). In the proximal jejunal segment of the rats treated with LPS, mucosal to serosal flux of digoxin was significantly enhanced compared to that of control (p < 0.05). Efflux of digoxin, which was taken up by intestinal epithelium, to mucosal perfusate was significantly blunted in the jejunum treated with LPS (p < 0.05), which indicates that the LPS treatment reduced the P-gp activity in rat small intestine. These findings suggest that the suppression of CYP3A and P-gp activities may be involved in the mechanism of elevated blood concentrations of cyclosporine and tacrolimus during enteritis-induced diarrhea. To prevent a drug-induced adverse effect, dose of a drug, which is a substrate of CYP3A or P-gp, should be reduced during such an episode.

Reductions in hepatic oxygen supply may reduce the oxidative metabolism of drugs, including tacrolimus. We encountered a patient (2.3-year-old girl) with hypoxemia [arterial oxygen tension (PaO2) 40.9 mmHg in room air] due to hepatopulmonary syndrome who had undergone living related liver transplantation. After transplantation, tacrolimus was initially administered by continuous intravenous infusion, and her PaO2 was maintained at more than 50 mmHg [72.8+/-10.4 (SD) mmHg] by oxygen supplementation. Apparent clearance of tacrolimus (calculated as: the infusion rate of tacrolimus/blood concentration) in the patient (0.075 l/h per kg) was comparable to those of non-hypoxemic control pediatric cases (0.092+/-0.014 l/h per kg, n=7, mean age 2.2 years, PaO2 149.2+/-41.5 mmHg), except for the acute decline in the early period after transplantation. These findings suggest that the reduction in tacrolimus clearance is negligible when arterial oxygen tension is maintained at more than 50 mmHg, even in patients with hypoxemia.

The objective of this study was to characterize the pharmacokinetics and immunosuppression of a tacrolimus-loaded biodegradable microsphere (TLBM) in rats. We prepared TLBM. DA/Slc rats were given TLBM at a dose of 1.6 mg/kg (n = 9), 2.4 mg/kg (n = 5), or 7.2 mg/kg (n = 7) tacrolimus contents by a single subcutaneous administration to achieve sustained release over a long period. DA/Slc rats were given TLBM by a single subcutaneous administration at a dose of 4.8 mg/kg (n = 6) tacrolimus contents to clarify the main site of TLBM uptake in the organs. In the rat liver transplantation model, the recipients were given TLBM at a dose of 0.16 mg/kg (n = 5), 2.4 mg/kg (n = 4), or 4.8 mg/kg (n = 5) tacrolimus contents by a single subcutaneous administration on the first day after operation. Overall survival days were compared. Continuous flat parallel concentration profiles were significant for 10 days from the first day after a single subcutaneous administration of TLBM (P

Background. The effect of pediatric partial liver transplantation on hypersplenism has not yet been clarified. Methods. Fifty-five consecutive pediatric patients who underwent living-donor liver transplantation were analyzed. The volume of the spleen was measured by computed tomography, and the spleen volume-to-standard spleen volume ratio (R) was calculated in each patient. The platelet counts were examined preoperatively and at 1, 6, 12, 18, 24, 36, and 48 months after the operation. The rate of the decline in this ratio during 1 year was calculated, and correlations with clinical factors were examined. Results. The ratio decreased gradually after the operation in all of the patients except for three with an eventful postoperative course. The rate of the reduction in R within 1 year after the operation was well correlated with preoperative R (R 0 ; P

BACKGROUND In living-related partial liver transplantation, the feasibility and safety of using left-sided liver grafts from donors with aberrant hepatic arteries remains to be evaluated. METHODS Between 1996 and 2000, we harvested left-sided liver grafts from 101 living donors. Hepatic arterial variation in the donors was classified into three types: type I (n=69), normal anatomy; type II (n=24), aberrant left hepatic artery arising from the left gastric artery; and type III (n=8), replaced right hepatic artery arising from the superior mesenteric artery. We performed arterial reconstructions using the donor's left hepatic artery in 70 cases (69 in type I, 1 in type II), an aberrant left hepatic artery in 24 cases (23 in type II, 1 in type III), and the common hepatic artery in 7 cases (all in type III). RESULTS The diameter and length of the anastomosed hepatic artery were larger (2.5+/-0.7 vs. 2.0+/-0.8 mm, P=0.03) and longer (42.0+/-14.7 vs. 9.0+/-7.3 mm, P

The optimal doses of tacrolimus (FK) needed to reach and maintain a target blood level vary among cases of living donor liver transplantation (LDLT). One hundred and twenty four LDLTs in 122 patients were included in this study. Tacrolimus was administered by continuous intravenous infusion at a rate of 2.5 microg/kg/h just after the operation. The time needed to reach the target blood level and the dose needed to maintain this level for 1 week (17-18 ng/mL) were defined as the initial duration (ID) and secondary dose (SD), respectively. In the first 100 LDLTs, the correlations between ID or SD and some clinical factors were examined and equations for predicting ID or SD were derived. In the latest 24 LDLTs, FK was administered using these equations and the actual and calculated ID and SD values were compared. A multiple regression analysis revealed that only the graft weight/recipient standard liver volume (GW/SLV) ratio (%) correlated with ID or SD. Stepwise regression analysis led to the equations ID (h) = 0.4 x GW/SLV ratio + 0.2; SD (microg/kg/h) = 0.02 x GW/SLV ratio - 0.4. Simple regression analysis revealed a significant correlation between the actual and calculated ID and SD values (p < 0.0001). Initial duration and SD can be estimated from equations using the GW/SLV ratio.

Patients with severe liver diseases, such as liver cirrhosis and biliary atresia, have low natural killer (NK) cell activity. The relations between NK activity and measures of liver function, including serum levels of total bilirubin, total bile acids, bile acid components, aspartate aminotransferase, and alanine aminotransferase, and platelet count were examined in patients with biliary atresia (6 boys and 6 girls; mean age, 4.8 ± 5.7 years) and patients with liver cirrhosis due to hepatitis C virus infection (10 men and 2 women; mean age, 54.3 ± 13.8 years). Univariate analysis showed that platelet count was positively correlated with NK activity in patients with biliary atresia (r = 0.611, P < 0.05). Serum levels of free chenodeoxycholic acid were negatively correlated with NK activity both in patients with biliary atresia (r = −0.647, P < 0.05) and in patients with hepatitis C virus-related liver cirrhosis (r = −0.876, P < 0.01). None of the other free bile acids or conjugated bile acids or other indicators of liver function were correlated with NK activity. Multiple stepwise regression analysis showed that only levels of free chenodeoxycholic acid were independently correlated with NK activity. All patients with biliary atresia underwent liver transplantation from living related donors. NK activity had increased significantly two months after transplantation (from 24.1 ± 20.2% to 49.2 ± 12.5%, P < 0.01). In contrast, levels of free chenodeoxycholic acid in transplant recipients had decreased significantly two months after transplantation (from 1.22 ± 1.16 to 0.26 ± 0.21 μmol/l, P < 0.05). In conclusion, in patients with biliary atresia or liver cirrhosis, NK activity in peripheral blood decreases, mostly because of free chenodeoxycholic acid.

Along with the increasing need for living-donor liver transplantation (LDLT), the issue of organ shortage has become a serious problem. Therefore, the use of organs from elderly donors has been increasing. While the short-term results of LDLT have greatly improved, problems affecting the long-term outcome of transplant patients remain unsolved. Furthermore, since contradictory data have been reported with regard to the relationship between donor age and LT/LDLT outcome, the question of whether the use of elderly donors influences the long-term outcome of a graft after LT/LDLT remains unsettled. To address whether hepatocyte telomere length reflects the outcome of LDLT, we analyzed the telomere lengths of hepatocytes in informative biopsy samples from 12 paired donors and recipients (grafts) of pediatric LDLT more than 5 years after adult-to-child LDLT because of primary biliary atresia, using quantitative fluorescence in situ hybridization (Q-FISH). The telomere lengths in the paired samples showed a robust relationship between the donor and grafted hepatocytes (r = 0.765, p = 0.0038), demonstrating the feasibility of our Q-FISH method for cell-specific evaluation. While 8 pairs showed no significant difference between the telomere lengths for the donor and the recipient, the other 4 pairs showed significantly shorter telomeres in the recipient than in the donor. Multiple regression analysis revealed that the donors in the latter group were older than those in the former (p = 0.001). Despite the small number of subjects, this pilot study indicates that donor age is a crucial factor affecting telomere length sustainability in hepatocytes after pediatric LDLT, and that the telomeres in grafted livers may be elongated somewhat longer when the grafts are immunologically well controlled.

The influence of HLA compatibility on acute rejection in cadaveric liver transplantation is not clearly defined, and that in living related liver transplantation (LRLT) has only been poorly examined. Few studies have focused solely on a pediatric population. Fifty-eight cases of pediatric LRLT were analyzed. Patient and graft survival rates and postoperative complications were assessed. The relationship between the incidence of acute rejection and HLA matching and some preoperative and intraoperative transplant recipient factors, including age, preoperative aspartate aminotransferase level, total bilirubin level, prothrombin time, ascites, donor-recipient blood group type and sex match, donor age, surgical time, anhepatic phase duration, volume of blood loss, and graft weight to standard liver volume, was examined. Patients with HLA-A zero mismatching (P = .04) or a greater volume of blood loss per body weight (P = .004) had a significantly lower chance of rejection within 6 weeks after LRLT. Our results show that in LRLT, a graft from an HLA-A zero-mismatched donor may be advantageous because it provides a lower chance of early acute rejection.

L'inhibiteur de la Trypsine Urinaire (UTI) est produit par le foie et excrete dans les urines durant les infections ou tumeurs malignes du foie. Nous proposons d'evaluer une possible implication d'UTI dans l'atresie des voies biliaires (BA). La fonction hepatique etait utilisee pour diviser 34 patients apres intervention pour atresie des voies biliaires en: Groupe 1 (n=25), anicterique, (bilirubine totale [T-bil] 2,0 mg/dl) avec des fonctions hepatique anormales et des episodes repetes de cholangite. 26 sujets du meme âge avec aucune histoire hepatique etaient etudies comme controles. L'UTI etait mesure dans les urines utilisant une double methode radio-immune, et par une technique immunohisto-chimique dans la biopsie hepatique. L'excretion d'UTI etait aussi apprecie durant les cholangites. L'UTI urinaire etait significativement plus importante dans le Groupe 1 que dans le Groupe 2 ou les controles. Durant les episodes de cholangite, l'UTI urinaire augmentait significativement chez les patients du Groupe 1 mais restait constante chez les patients du Groupe 2, et il y avait une reaction immuno-histo-chimique importante vis-a-vis de l'UTI dans les cellules parenchymateuse du foie et dans les cellules du Groupe 1 alors qu'il y avait une faible reaction dans le groupe controle et aucune reaction dans le Groupe 2. L'UTI peut-etre utilisee pour monitorer les reserves hepato-cellulaires dans les maladies evolutives telles que les atresie des voies biliaires. L'administration prophylactique d'UTI peut aussi etre benefique et peut-etre l'objet de futures recherches.

Living-related liver transplantation (LRLT) has been accepted as an effective treatment of choice for pediatric patients but its feasibility for adult patients is limited because of graft size disparity. Kawasaki and colleagues have shown that the donor’s left liver (without the caudate lobe) can be used as a maximal-for-size graft to adults if the ratio of the predicted graft volume (GV) to the recipient’s standard liver volume (SV) is more than one-third. When the graft is too small, auxiliary implantation of the left liver or use of the right liver can be an option in patients under urgent situations. Recently Miyagawa and colleagues reported a patient who received a left liver with caudate lobe graft, but they did not reconstruct the drainage vein of the caudate lobe, which may cause lobe congestion and dysfunction. We report a new technique by which the left liver plus caudate lobe is implanted with complete reconstruction of the vessels relevant to the caudate lobe.

Cholestatic effects have been reported for cyclosporine (CsA), but information is still limited for tacrolimus (TCR). The purpose of this study was to investigate the influence of TCR on biliary bile acid and lipid composition as compared with CsA, using a continuously bile-drained rat model. Adult male Wistar rats received TCR (0.4 mg/kg, 1 mg/kg, and 4 mg/kg) or CsA (2.5 mg/kg, 10 mg/kg, and 25 mg/kg) by intramuscular injection (i. m.) daily for 10 days. On day 7, the common bile duct of all rats was cannulated, then bile was continuously collected for the following 3 days. Bile flow, bile acid secretion rate (BASR), and biliary lipids secretion were measured for each of the groups. TCR increased bile acid-dependent flow (BADF) but with no statistical significance. However, this agent did not influence total bile flow and biliary lipids secretion, while bile acid-independent flow (BAIF) was significantly reduced and bile acid synthesis (mainly cholic acid, CA, synthesis) was increased. In contrast, CsA was cholestatic, showing a tendency to reduce both BADF and BAIF. BASR was dose-dependently suppressed, especially in chenodeoxycholic acid (CDCA). Furthermore, biliary lipids secretions were also significantly decreased under a higher dose of CsA. TCR increased BADF with no influence on total bile flow, having a stimulating effect on CA production, although CsA dose-dependently diminishes CDCA production and consequently reduced bile secretion. Our results suggest that TCR is a less effective agent on cholestasis as compared to CsA.

Background : Fetal and newborn intestine often are revascularized after subcutaneous transplantation without surgical vascular anastomosis. However, the mechanism of this ability remains unclear. Methods : First, the ability of natural revascularization in newborn organs was tested. Newborn organs in whole (liver, kidney, heart, intestine, spleen, and pancreas) were grafted into the subcutaneous tissue of the adult rat and evaluated histopathologically 2 weeks after transplantation. Second, expression of vascular endothelial growth factor (VEGF) mRNA in the intestinal graft was determined before and after transplantation. Finally, we tested whether the free graft survival of newborn intestine was interrupted by TNP-470, an antiangiogenic agent. Results : Spleen and intestine were revascularized at a higher rate (91.6%, 75%, respectively), and kidney and heart grafts survived at a lower rate (41.7%, 25%, respectively). But all of liver and pancreas grafts failed to be revascularized. VEGF mRNA was not induced in the course of revascularizing. Furthermore, TNP-470 did not interfere with neovascularization of the newborn intestinal graft in vivo. Conclusions : Each organ had an organ-specific angiogenic activity. Neovascularization of intestinal graft was not dependent on VEGF expression.

Background Hepatic artery thrombosis after liver transplantation remains a significant cause of graft loss and death. Retransplantation is a difficult option after living-related liver transplantation in Japan. Methods Twenty-seven patients underwent living-related liver transplantation with left-sided liver grafts donated from their relatives. The hepatic artery was anastomosed end to end under a surgical microscope. Anticoagulant therapy was maintained for 2 weeks after operation. Routine post-transplant Doppler ultrasonography together with serum blood tests were performed twice a day during the first 2 weeks. Results Three patients developed hepatic artery occlusion, which was identified by routine Doppler ultrasonography before the serum transaminase values increased on days 7, 7 and 3 after surgery respectively. In two of the three patients, no apparent arterial thrombosis was recognized and vasospasm was therefore considered to be the cause of the occlusion. Arterial patency was restored by urgent revascularization with reanastomosis in all patients, but one patient with a functional graft died from a cerebral haemorrhage on day 47. Conclusion Early diagnosis of hepatic artery occlusion by routine Doppler ultrasonography and revascularization of the graft is an indispensable strategy for preventing graft loss after living-related liver transplantation.

Background. Deoxyspergualin (DSG), a potent immunosuppressive drug, has been clinically used as a rescue therapy for acute graft rejection. However, DSG has severe adverse effects that limits its use. Here, we examined the optimized therapeutic protocol for DSG using chronopharmacological profiles of it. Methods. First, a dosing time-dependent difference in the toxicity and efficacy of DSG was determined using a heterotopic heart transplantation model. Second, chronokinetics of DSG were examined to reveal the mechanism for dosing time-dependent differences in the effect. Results. In rats treated with DSG at the active period, bone marrow suppression and damage of small intestine were significantly severe. However, no significant difference was found in cardiac allograft survival and pharmacokinetics according to the timing of drug administration. Conclusions. The toxicity of DSG varied with the dosing time, whereas its efficacy did not. The chronopharmacological approach may provide merits for immunosuppressive therapy with DSG in clinical organ transplantation.

It is very difficult to collect bile secretions from animals for extended periods of time. We compared the use of saline or water as drinking fluids to sustain the animals, which were being continuously drained of bile. Complete bile drainage was performed in 16 male Wistar rats by surgical intervention. After surgery, 8 rats were given tap water, and the other 8 were given normal saline for water. The rats that received water rapidly lost weight after bile drainage, and all died within 8 days after the operation. In contrast, all rats that drank saline maintained their body weight and survived 14 days or longer after surgery. Serum biochemistry of the rats with water intake on the third day after bile drainage revealed hyponatremia, hypochloremia, and acute renal failure resulting in hyperkalemia. In contrast, electrolyte balance and renal function were normal in the rats with saline intake, and bile was secreted continuously with a circadian rhythm. These results clearly demonstrate that saline as drinking water is essential to the replacement of lost fluids and loss of electrolytes due to bile drainage. Further, saline proved efficacious for sustaining experimental animals undergoing continuous bile collection.

We monitored the serial changes of natural killer cell (NK) activity in eight recipients of living-related liver transplantation. The HLA types of all eight patients were haplotypically identical with those of their donors. Tacrolimus and methylprednisolone were used for immunosuppression. The NK activity before transplantation was 24.1 ± 20.2 % which is surprisingly low when compared with the value for normal individuals (67.7 ± 13.2 %, P < 0.01) or a liver dysfunction group (49.4 ± 21.9 %, P < 0.05). Serial changes in NK activity revealed a minimum of 6.1 ± 3.6 % 1 week after transplantation, gradually increasing to 49.2 ± 12.5 % at 2 months after transplantation. These results suggest that the diseased liver might play an important role in the suppression of NK activity.

To the Editor: We greatly appreciate the thoughtful comments of Detry et al. relating to our report of liver transplantation from a living donor with early gastric cancer (1). The issues posed herein consist of two ethically important aspects surrounding living-related transplantation: the adequacy of a ’patient’ with early cancer as a donor, and the risk of a donor involved in combined surgery simultaneously performing graft procurement plus another major operation. As Detry et al. maintain, the risk of cancer transmission to the recipient with the graft is not null even if the donor’s cancer remains in its early stage. We certainly estimated the risk not as zero but as very low on the basis of the preoperative diagnostics as we discussed in our article. Preoperative evaluation of early gastric cancer in terms of depth of invasion and predictive assessment of metastasis according to the depth of invasion are extremely accurate, though not 100%, thanks to the decades of efforts of endoscopists and mountains of data collected by gastroenterologists and surgeons in our country. Nevertheless, such data have derived from noncompromised patients. As Detry et al. appropriately point out, immunosuppressive recipients are more susceptible to cancer ’metastasis’ (transmission) whose risk should increase in synchronous cancergraft surgery due to circulating malignant cells as compared to metachronous graft procurement sometime after cancer resection. Our perception was that the low risk of cancer transmission to the recipient compared to the significant risk of death without transplantation warranted proceeding in this particular circumstance. Regarding the donor’s increased risk in concurrent surgery, our article failed to present sufficient data on the safety of combined surgery. According to nationwide surveys (2,3), mortality of gastrectomy for early gastric cancer is satisfactorily low (0‐0.6%), and that of hepatic graft procurement in living donors is one in 2668 donors in Japan from 1989 to 2003 (4). Very few data are available on the morbidity and mortality of synchronous surgery combining gastrectomy and hepatectomy mainly due to rarity of cases of gastric cancer with operable hepatic metastases. In this regard, the results of colorectal resection combined with simultaneous hepatectomy for operable deposits in the liver may provide some hints. At our institution the overall mortality of combined resection of colorectal cancer and hepatic lobes was extremely low (0%, 0 of the 35 cases) whether the hepatectomized lobe was left or right. We should not, however, extrapolate from these outcomes the safety of hepatic graft procurement combined with another major surgery. As Detry et al. suggest, hepatic graft procurement, especially from the right lobe, still remains marginal with documented morbidity and mortality, denying additional surgical procedures.

Biliary complications remain a major concern after living donor liver transplantation. We describe a pediatric case who underwent a successful endoscopic balloon dilatation of biliary-enteric stricture following living donor liver transplantation using a newly developed method of enteroscopy. The 7-year-old boy with late biliary stricture of choledochojejunostomy was admitted 6 years after transplantation. Since percutaneous transhepatic cholangiography was technically difficult in this case, endoscopic retrograde cholangiography was performed using a double-balloon enteroscope under general anesthesia. The enteroscope was advanced retrograde through the duodenum, jejunum, and the leg of Roux-Y by the double-balloon method, and anastomotic stricture of choledochojejunostomy was clearly confirmed by endoscopic retrograde cholangiography and endoscopic direct vision. Balloon dilatation was performed and the anastomosis was expanded. Restenosis was not noted as of 2 years after the treatment. In conclusion, endoscopic balloon dilation of biliary-enteric anastomotic stricture using a new enteroscopic method can be regarded as an alternative choice to percutaneous transhepatic management and surgical re-anatomists.

In view of the relative scarcity of pediatric cadaveric donors, living-related liver transplantation has recently been accepted as an alternative approach. It is also the only method of liver transplantation available in countries where cadaveric organ procurement is prohibited. Here we describe our experience of living-related liver transplantation in 17 patients at Shinshu University Hospital. The safety of the donor operation is of paramount importance in this type of liver transplantation. In Japan, retransplantation is very difficult in the event of the liver graft becoming nonfunctional. We have therefore placed emphasis on the donor hepatectomy technique as well as on surgical procedures and postoperative care to prevent graft loss in the recipient. Fifteen of the 17 patients who received liver transplants are currently alive; and 1 died of cytomegalovirus infection, and 1 of pulmonary complications. The actuarial 1-year survival rate for our series, determined by Kaplan-Meier analysis, was 89.5%. Although living-related liver transplantation requires a complicated surgical procedure, it has achieved reasonable results for both donors and recipients. We consider that living-related liver transplantation is a useful and reasonable option for patients requiring liver transplantation.

In the field of pediatric living donor liver transplantation, the indications for apheresis and dialysis, and its efficacy and safety are still a matter of debate. In this study, we performed a retrospective investigation of these aspects, and considered its roles. Between January 2008 and December 2010, 73 living donor liver transplantations were performed in our department. Twenty seven courses of apheresis and dialysis were performed for 19 of those patients (19/73; 26.0%). The indications were ABO incompatible-liver transplantation in 11 courses, fluid management in seven, acute liver failure in three, renal replacement therapy in two, endotoxin removal in two, cytokine removal in one, and liver allograft dysfunction in one. Sixteen courses of apheresis and dialysis were performed prior to liver transplantation for 14 patients. The median IgM antibody titers before and after apheresis for ABO blood type-incompatible liver transplantation was 128 and eight, respectively (P0.05). Eleven courses of apheresis and dialysis were performed post liver transplantation for 10 patients. The median PaO2/FiO2 ratio before and after dialysis for fluid overload was 159 and 339, respectively (P0.05). No bleeding or technical complications attributable to apheresis and dialysis occurred. The 1-year survival rate of the patients was 100%. Apheresis and dialysis in pediatric living donor liver transplantation are effective for antibody removal in ABO-incompatible liver transplantation, and fluid management for acute respiratory failure.

Objectives Cholestatic liver disease (CLD) is the main indication for liver transplantation in children. This retrospective study evaluated the outcomes of living donor liver transplantation (LDLT) in children with CLD. Methods One hundred fifty-nine children with CLD who underwent 164 LDLT between May 2001 and May 2011 were evaluated. Their original diseases were biliary atresia ( n = 145, 91%), Alagille syndrome ( n = 8, 5%), primary sclerosing cholangitis ( n = 2), and the others ( n = 4). The mean age and body weight of the recipients at LDLT was 42 ± 53 months and 14.0 ± 11.0 kg, respectively. Results Parents were living donors in 98%. The left lateral segment was the most common type of graft (77%). There were no reoperations and no mortality in any living donor. Recipients' postoperative surgical complications consisted mainly of hepatic arterial problems (7%), hepatic vein stenosis (5%), portal vein stenosis (13%), biliary stricture (18%), intestinal perforation (3%). The overall rejection rate was 31%. Cytomegalovirus infection and Epstein-Barr virus disease were observed in 26% and 5%, respectively. Retransplantation was performed five times in four patients; the main cause was hepatic vein stenosis ( n = 3). Four patients died; the main cause was gastrointestinal perforation ( n = 2). The body height of Alagille syndrome patients less than 2 years old significantly improved compared with older patients after LDLT. The 1-, 5-, and 10-year patient survival rates were 98%, 97%, and 97%, respectively. Conclusions LDLT for CLD is an effective treatment with excellent long-term outcomes.