眞田 幸弘

BACKGROUND: 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. METHODS: 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. RESULTS: 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). CONCLUSION: 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.

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.

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 < 0.05). 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 (P < 0.05). 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: A surgeon must be aware of hepatic vascular variations to safely perform living-donor liver transplant. The ramification patterns of the hepatic veins with tributaries for left lobe graft outflow venoplasty should be evaluated preoperatively with 3-dimensional computed tomography of the donor. MATERIALS AND METHODS: Twenty-four potential donors were examined between October 1999 and July 2006 for living-donor liver transplant using the left lobe. They underwent triphasic helical computed tomography of the liver on a multidetector helical computed tomographic scanner. All images, including 2-dimensional reformation and 3-dimensional reconstructed models with maximum intensity projection and volume rendering, were sent to a workstation for postprocessing. RESULTS: The ramification patterns of the left and middle hepatic vein were classified into 2 groups; they formed a common trunk (type 1), which had 3 variations; type 1A (13 cases): in which the left hepatic vein and the middle hepatic vein without any tributaries on their confluence; type 1B (8 cases): in which there was venous confluence in the left hepatic vein with the left superficial vein and middle hepatic vein; type 1C (2 cases): in which the hepatic venous confluence in the left hepatic vein and middle hepatic vein and the left superficial vein directly joining into the inferior vena cava; type 2 (1 case) had the left hepatic vein and middle hepatic vein joining into the inferior vena cava separately; type 1B underwent 2 venoplasty procedures, but the others underwent only a single venoplasty. CONCLUSIONS: We demonstrated the anatomic interrelation of the hepatic veins for hepatic outflow venoplasty of adult left lobe living-donor liver transplant with 3-dimensional computed tomography scanning to help surgeons preoperatively determine the appropriate technique or form of reconstruction.

BACKGROUND: 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. METHODS: 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. RESULTS: 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 < 0.001). Regression analysis demonstrated a negative correlation of the normalized telomere-centromere ratio with the pediatric end-stage liver disease score in biliary atresia (p < 0.001). CONCLUSIONS: Telomere length analysis using quantitative fluorescence in situ hybridization could be an objective indicator of hepatocellular reserve capacity in patients with biliary atresia, and excessive telomere shortening supports the early implementation of liver transplantation.

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.

BACKGROUND AND AIMS: Congenital extrahepatic portosystemic shunt (CEPS) is a rare venous malformation in which mesenteric venous blood drains directly into the systemic circulation. It is still a matter of debate whether conservative or operative strategies should be used to treat symptomatic CEPS. The aim of this study was to evaluate the role of operative intervention in the management of CEPS. METHODS: Between June 2004 and August 2010, 6 consecutive patients with symptomatic CEPS were treated in our department. There were 3 male and 3 female patients, with a median age of 3.5 years (range, 1-8). Their demographic, clinical, and laboratory data were analyzed. All patients were scheduled to undergo shunt ligation or liver transplantation (LT). RESULTS: Living donor LT was carried out in 4 patients, and shunt ligation in 2. After a median follow-up of 25 months, all the patients are alive currently with marked relief of symptoms. CONCLUSION: Shunt ligation or LT for symptomatic CEPS is potentially curative.

There are no objective and concrete guidelines for the management of Ornithine transcarbamylase deficiency (OTCD). Based on previous findings, we hypothesized that patients with OTCD have a low Ornithine transcarbamylase (OTC) activity in the liver, and therefore it would be better to determine the appropriate indications and optimal timing for liver transplantation (LT) based on the OTC activity. However, few data have so far been accumulated on the OTC activity in cases that are indicated for LT. The purpose of the present study was to clarify the OTC activity in cases that were indicated for LT. This study involved thirteen children with OTCD (8 males and 5 females) who underwent LT, and two females with OTCD who did not require LT. The OTC activity of the neonatal onset type ranged from 0% to 7.2%, while that of the late onset type who underwent LT ranged from 4.4% to 18.7%. The OTC activity of the late onset type which did not require LT was 33-38% based on a preoperative needle liver biopsy. Some late onset patients that underwent LT, showed an activity that was as low as that observed in the neonatal onset cases. This is the first report to show the results of measuring the OTC activity for serial OTCD cases indicated for LT. OTC activity might be an indicator to determine the indications for and the timing of LT in the late onset type, however, further investigations are necessary.

Hepatic artery complications after living donor liver transplantation (LDLT) can directly affect both graft and recipient outcomes. For this reason, early diagnosis and treatment are essential. In the past, relaparotomy was generally employed to treat them. Following recent advances in interventional radiology, favorable outcomes have been reported with endovascular treatment. However, there is ongoing discussion regarding the best and safe time for definitive endovascular interventions. We herein report a retrospective analysis for six children with early hepatic artery complication after pediatric LDLT who underwent endovascular treatment as primary therapy at our institution. We evaluate the usefulness of endovascular treatment for hepatic artery complication and its optimal timing. The mean patient age was 11.9 months and mean body weight at LDLT was 6.7 kg. The mean duration between the transplantation and first endovascular treatment was 5.3 days. Five of the six patients were technically successful treated by only endovascular treatment. Of these five patients, two developed biliary complications. Endovascular procedures were performed 10 times in six patients without any complications and nine of the 10 procedures were successful. By selecting optimal devices, our findings suggest that endovascular treatment can be feasible and safe in the earliest time period after pediatric LDLT.

PURPOSE: 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. PATIENTS AND METHODS: 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. RESULTS: 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. CONCLUSION: 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.

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.

PURPOSE: 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. PATIENTS AND METHODS: 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). RESULTS: 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 (p < 0.01). Duration of surgery was an independent risk factor (p = 0.05). CONCLUSION: 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.

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.

Portal vein stenosis (PVS) after living donor liver transplantation (LDLT) is a serious complication that can lead to graft failure. Few studies of the diagnosis and treatment of late-onset (> or = 3 months after liver transplantation) PVS have been reported. One hundred thirty-three pediatric (median age 7.6 years, range 1.3-26.8 years) LDLT recipients were studied. The patients were followed by Doppler ultrasound (every 3 months) and multidetector helical computed tomography (once a year). Twelve patients were diagnosed with late-onset PVS 0.5-6.9 years after LDLT. All cases were successfully treated with balloon dilatation. Five cases required multiple treatments. Early diagnosis of late-onset PVS and interventional radiology therapy treatment may prevent graft loss.

To investigate the relationship between the pretransplant LCT results and the outcome after pediatric LDLT in a single center. The clinical data of 76 children undergoing 79 LDLTs including three retransplantations from May 2001 to January 2006 were retrospectively analyzed. All of the children had end-stage liver disease, and their median age was 1.4 yr (range, six months to 16.5 yr). Immunosuppressive therapy consisted of cyclosporine- or FK-based regimens with steroids. The children were classified into two groups (positive or negative) according to the pretransplant LCT results. The incidences of post-transplant surgical complications and of rejection episodes were compared. The relationship between the pretransplant LCT results and patient and graft survival rates was also analyzed. Seventy-nine pretransplant crossmatch tests were done; 13 (16.5%) were positive, and 66 (83.5%) were negative. No significant difference was found in the pretransplant clinical factors between two crossmatch groups. There was no significant difference between the groups in the incidence of vascular and biliary tract complications, in the rate of early or steroid-resistant cellular rejections, or in one- and three-yr patient (91.7%, 91.7%, respectively, in the positive group, 93.5%, 93.5%, respectively, in the negative group, p = 0.80) and graft (92.3%, 92.3%, respectively, in the positive group, 88.8%, 86.4%, respectively, in the negative group, p = 0.63) survival. The present study demonstrates that there is no reason to do pretransplant LCT to select the living donor for pediatric LDLT.

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.

We evaluated the growth curves of children with BA after LDLT, and identified factors influencing growth velocity one-yr after LDLT (DeltaZ). The clinical data of 51 children with BA, who had an LDLT at our center from 2001 to 2005, were retrospectively reviewed. The Z scores for height and weight, and DeltaZ were studied. The correlation between DeltaZ and various clinical factors was evaluated statistically. Multivariate stepwise analyses were performed for DeltaZ. The average height and weight Z scores at the time of LDLT were -1.34 +/- 1.36 (+/-s.d.) and -0.78 +/- 1.15, respectively. Among 30 BA recipients with stable liver function after transplant, weight returned to normal one-yr post-transplantation. However, height did not return to normal even by the third post-transplantation year. On multivariate analyses, 73% of the variance in height DeltaZ could be accounted for by factors such as standardized height at the time of LDLT (proportion of variance: 38%), number of steroid pulse treatments (17%), donor age (10%), and the presence of HVS (9%). Fifty-four percentage of the variance in weight DeltaZ could be accounted for by factors such as standardized weight at the time of LDLT (37%) and the total steroid dose given (17%). Height and weight status at the time of LDLT likely have the strongest impact on DeltaZ. Additional factors include steroid exposure, age of the living donor, and presence of HVS, all of which should be considered to improve post-transplantation growth.

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.