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Maternal T cells from perinatal transplacental passage have been identified in up to 40% of patients with severe combined immunodeficiency (SCID). Although engrafted maternal T cells sometimes injure newborn tissue, liver failure due to maternal T cells has not been reported. We rescued a boy with X-linked SCID who developed liver failure due to engrafted maternal T cell invasion following living donor liver transplantation (LDLT) following unrelated umbilical cord blood transplantation (UCBT). After developing respiratory failure 3 weeks postpartum, he was diagnosed with X-linked SCID. Pathological findings showed maternal T cells engrafted in his liver and hepatic fibrosis gradually progressed. He underwent UCBT at 6 months, but hepatic function did not recover and liver failure progressed. Therefore, he underwent LDLT using an S2 monosegment graft at age 1.3 years. The patient had a leak at the Roux-en-Y anastomosis, which was repaired. Despite occasional episodes of pneumonia and otitis media, he is generally doing well 6 years after LDLT with continued immunosuppression agents. In conclusion, the combination of hematopoietic stem cell transplantation (HSCT) and liver transplantation may be efficacious, and HSCT should precede liver transplantation for children with X-linked SCID and liver failure.

Liver cirrhosis due to secondary sclerosing cholangitis caused by Langerhans cell histiocytosis (LCH) has a poor prognosis, and liver transplantation is the definitive treatment. However, the optimal timing has not been established. We report a 2-year-old girl with LCH-related liver cirrhosis who successfully underwent liver transplantation before progressing to severe liver dysfunction. Physical examination revealed a tumor on her palate. Biopsy was performed, and a diagnosis of LCH was established, together with hepatomegaly, splenomegaly, and rashes. Percutaneous liver biopsy before treatment revealed extreme fibrosis and absence of LCH cells. After beginning chemotherapy, she experienced several delays in treatment and dose reductions because of unacceptable bone marrow suppression, worsening liver dysfunction, and cholangitis. However, tumor shrinkage was observed in both magnetic resonance imaging and BRAF V600E mutant allele titers in her plasma. Given the good treatment response, liver transplantation was conducted. The postoperative course was uneventful, and chemotherapy was resumed 34 days after liver transplantation. Subsequent maintenance treatment was completed with no severe adverse effects. To prevent perioperative complications due to exacerbation of liver dysfunction and possible discontinuation of chemotherapy, liver transplantation should be considered before development of end-stage liver failure, provided that the original disease is well controlled.

Aim Down syndrome has been considered an independent risk factor for respiratory syncytial virus (RSV) infection. Palivizumab, an anti-RSV humanised monoclonal antibody, was currently approved for all children with Down syndrome in Japan. To investigate the change in RSV-associated hospitalisation (RSVH) rates before and after the universal approval of palivizumab in Japan in 2013, we conducted a nationwide retrospective survey. Methods We conducted a nationwide, retrospective, questionnaire survey across paediatric institutions in Japan. The recruited children with Down syndrome were divided into two groups: those born April 2010 to March 2013 (2010-2012 cohort) and those born April 2013 to March 2016 (2013-2015 cohort). Results Of the 664 institutions, 321 (48.3%) replied, and a total of 3929 children with Down syndrome were registered. The percentage of children who received palivizumab increased from 49.2% to 82.2%. The cumulative RSVH rate showed a decreased trend in the 2013-2015 cohort (OR, 0.83; 95%CI, 0.63-1.10), while the rate of these children (without CHD and born at a gestational age ≥ 36 weeks) was significantly decreased in the 2013-2015 cohort (OR, 0.56; 95%CI, 0.34-0.92). Conclusion The cumulative RSVH rate tended to be decreased after approval for all children with Down syndrome although the result was not significant.

Background Liver transplantation is the most suitable treatment option available for end-stage liver disease. However, some patients require retransplantation, despite medical advances that have led to improved survival. We aimed to compile a definitive, nationwide resource of liver retransplantation data in Japan, seeking to identify the predictors of patient survival posttransplantation. Methods Questionnaires were sent to 32 institutions that had conducted 281 retransplantations before 2015. Results Among the 265 patients included in this study (142 pediatric cases), the average age at primary transplantation was 23 years, and retransplantation was performed after an average of 1468 days. The main indication for retransplantation was graft rejection (95 patients). Living-donor liver transplantation accounted for 94.7% of primary transplantations and 73.2% of retransplantations. Patient survival at 1, 3, or 5 years did not differ by type of transplantation but was better for pediatric (70.8%, 68.3%, and 60.1%, respectively) than for adult (57.2%, 50.4%, and 45.2%, respectively) recipients (P = 0.0003). Small-for-size syndrome, retransplantation within 365 days, and inpatient status at retransplantation were significant predictors of poor survival in pediatric cases. Retransplantation within 365 days and conditions warranting retransplantation were significant predictors of poor survival in adult patients. Conclusions In Japan, where >70% of retransplantations are performed using living donors, the indications and timing are different from those in previous reports from other countries, while maintaining comparable survival rates. Considering technical challenges, graft failure within 365 days should be thoroughly restricted to justify the use of living donor.

Acetaminophen (APAP) overdose is a common cause of drug-induced acute liver failure. Although hepatocyte cell death is considered to be the critical event in APAP-induced hepatotoxicity, the underlying mechanism remains unclear. Ferroptosis is a newly discovered type of cell death that is caused by a loss of cellular redox homeostasis. As glutathione (GSH) depletion triggers APAP-induced hepatotoxicity, we investigated the role of ferroptosis in a murine model of APAP-induced acute liver failure. APAP-induced hepatotoxicity (evaluated in terms of ALT, AST, and the histopathological score), lipid peroxidation (4-HNE and MDA), and upregulation of the ferroptosis maker PTGS2 mRNA were markedly prevented by the ferroptosis-specific inhibitor ferrostatin-1 (Fer-1). Fer-1 treatment also completely prevented mortality induced by high-dose APAP. Similarly, APAP-induced hepatotoxicity and lipid peroxidation were prevented by the iron chelator deferoxamine. Using mass spectrometry, we found that lipid peroxides derived from n-6 fatty acids, mainly arachidonic acid, were elevated by APAP, and that auto-oxidation is the predominant mechanism of APAP-derived lipid oxidation. APAP-induced hepatotoxicity was also prevented by genetic inhibition of acyl-CoA synthetase long-chain family member 4 or α-tocopherol supplementation. We found that ferroptosis is responsible for APAP-induced hepatocyte cell death. Our findings provide new insights into the mechanism of APAP-induced hepatotoxicity and suggest that ferroptosis is a potential therapeutic target for APAP-induced acute liver failure.

Early relaparotomy of adult recipients after living donor liver transplantation (LDLT) is significantly associated with poor prognosis. However, there are few reports focusing on pediatric recipients after LDLT. The aim of this study is to clarify the causes and outcomes of early relaparotomy after pediatric LDLT. A total of 265 pediatric recipients (272 LDLTs) transplanted from May 2001 to October 2015 were retrospectively analyzed. Early relaparotomy was defined as surgical intervention performed within 3 months after LDLT. Early relaparotomy was performed 49 times for 33 recipients (12.5%). The recipient and graft survival rates in the early relaparotomy group were significantly lower than those in the nonearly relaparotomy group, respectively (75.0% and 63.6% versus 96.6% and 95.8%; both P < 0.001). Left lateral segment grafts were used significantly more frequently in the nonrelaparotomy group (P = 0.01). According to the multivariate analysis, the preoperative Pediatric End-Stage Liver Disease (PELD)/Model for End-Stage Liver Disease (MELD) score of the early relaparotomy group was significantly higher than that of the nonearly relaparotomy group (13.7 versus 6.3; P = 0.04). According to the receiver operating characteristic curve, the preoperative PELD/MELD score cutoff point was 17.2. Early relaparotomy due to infectious causes led to significantly poorer graft survival than that due to noninfectious causes (P = 0.04). In conclusion, the recipient and graft survival rates of the early relaparotomy group were significantly lower than those of the nonearly relaparotomy group. A high preoperative PELD/MELD score was a risk factor for early relaparotomy. In particular, early relaparotomy due to infection showed a poor prognosis.

Purpose After undergoing the Kasai procedure for biliary atresia (BA), most patients develop severe splenomegaly that tends to be improved by liver transplantation. However, fluctuations in splenic volume long after transplantation remain to be elucidated. Patients and Methods Seventy-one consecutive patients who had undergone pediatric living donor liver transplantation (LDLT) for BA were followed up in our outpatient clinic for 5 years. They were classified into 3 groups according to their clinical outcomes: a good course group (GC, n = 41) who were maintained on only 1 or without an immunosuppressant, a liver dysfunction group (LD, n = 18) who were maintained on 2 or 3 types of immunosuppressants, and a vascular complication group (VC, n = 11). Splenic and hepatic volumes were calculated by computed tomography in 464 examinations and the values compared before and after the treatment, especially in the VC group. Results Splenic volume decreased exponentially in the GC group, with splenic volume to standard spleen volume ratio (SD) being 1.59 (0.33) 5 years after liver transplantation. Splenic volume to standard spleen volume ratios were greater in the VC and LD groups than in the GC group. Patients in the VC group with portal vein stenosis developed liver atrophy and splenomegaly, whereas those with hepatic vein stenosis developed hepatomegaly and splenomegaly. Interventional radiation therapy tended to improve the associated symptoms. Conclusions Fluctuations in splenic volume long after pediatric LDLT for BA may reflect various clinical conditions. Evaluation of both splenic and hepatic volumes can facilitate understanding clinical conditions following pediatric LDLT.

Biliary atresia (BA) is a progressive cholestatic disease that accounts for nearly 50% of patients referred for liver transplants [1]. Kasai portoenterostomy is the first-line standard treatment for BA and recommended to be performed within 60 days of birth to manage jaundice. However, even if yellowish stool can be eliminated, and a complete correction of the serum bilirubin level to below the normal range can be achieved, then up to half of all BA patients cannot make it through adolescence with their native liver and ultimately require liver transplantation (LT) [2, 3]. Complications of cirrhosis, including portal hypertension, ascites, variceal bleeding, and acute-on-chronic liver failure, are indications for LT [3, 4]. The extrahepatic complications associated with this disease, such as hepatopulmonary syndrome and portopulmonary hypertension, are also indications for LT [4].

BACKGROUND AND AIM Serum Mac-2 binding protein glycosylation isomer (M2BPGi) is a novel fibrosis marker for various chronic liver diseases. We investigated the ability of M2BPGi to predict liver fibrosis in liver transplant (LT) recipients. METHODS A total of 116 liver biopsies were performed in 113 LT recipients. The serum level of M2BPGi was also measured on the same day. The median age at LT and liver biopsy was 1.1 and 11.8 years, respectively. Serum M2BPGi levels and liver fibrosis status using METAVIR fibrosis score were compared. Immunohistological evaluation by anti-α-smooth-muscle actin (αSMA) was performed, and the relationship between αSMA positive rate and serum M2BPGi levels was investigated. RESULTS The median M2BPGi level was 0.78 (range, 0.22-9.50), and 65, 29, 16, 5, and 1 patient(s) had METAVIR fibrosis scores of F0, F1, F2, F3, and F4, respectively. In patients with F0 fibrosis, median M2BPGi level was 0.69 and was significantly lower than in patients with F1 (median 0.99, P F1: 0.716, > F2: 0.720, and > F3: 0.900. Three patients with acute cellular rejection showed high levels of M2BPGi, which decreased after the treatment. A positive correlation existed between M2BPGi levels and αSMA positive rate (r2 = 0.715, P

Smaller surgical incisions have recently been introduced in living donor liver procurement. This study used national data from Japan to clarify the present status of surgical incisions in living donor liver procurement.A nationwide, questionnaire-based survey related to 3121 donors and recipients was used. Donors were divided into 2 groups: left lateral segment graft (LLSG) procurement (n = 690) and other types (n = 2431). Incisions were classified into 6 types: type I, upper midline and bilateral subcostal; type II, upper midline and right subcostal; type III, upper midline and right subcostal to the right lateral margin of the abdominal rectus muscle; type IV, upper midline without laparoscopy; type V, upper midline with laparoscopy; and type VI, lower abdominal using the full laparoscopic technique. Types I, II, and III were regarded as standard, and types IV, V, and VI as small incisions.In LLSGs, blood transfusion and postoperative complication rates were significantly less frequent in the small incision group than in the standard group. In other graft types, there were no significant differences in blood transfusion, postoperative complication, and recipients' graft loss rates. The rates of wound extension during surgery were 2.8% and 2.1% in the small incision group in LLSGs and in other graft types, respectively. A small incision was adapted more frequently and postoperative complications were less common in high-volume centers.Various incisions have been adopted in living donor liver procurement. Donor safety and graft integrity appear to have been retained for donors receiving small incisions.

Background: Neonatal hemochromatosis (NH) is a rare but serious disease causing fulminant hepatic failure. The recurrence rate of NH in a subsequent infant of a mother with an affected infant is 70...

Background Health-related quality of life (HRQOL) is an important outcome in solid organ transplantation. This study evaluated and explored the factors of generic and transplant-specific HRQOL in Japanese pediatric and adolescent patients with biliary atresia (BA) after living donor liver transplant (LDLT). Methods A cross-sectional survey using anonymous questionnaires was completed between April and July 2015. Patient medical records were accessed. The Japanese version of Pediatric Quality of Life InventoryTM Generic Core Scales and Transplant Modules (child self-report and parent proxy-report) was administered. Results Participants consisted of 75 patients (mean age at survey, 9.6 years) and 74 parents. Japanese patients reported higher generic and transplant-specific HRQOL (total score) than that reported by US patients with BA after LT (US I; age at survey, 7.2 years) and by US patients after solid organ transplant (US II; age at survey, 11.3 years; LT, 53.8%; effect size, 0.55–0.96). Japanese parents, however, rated their children's generic HRQOL (total score) similar to that rated by the US I and II parents (0.13 and 0.30, respectively) and reported lower transplant-specific HRQOL (total score) than that reported by US II (0.26). Although the number of types of prescribed drugs was a common factor in HRQOL, most demographic and medical factors (e.g. child's age at survey and consultation frequency) varied with reporter (i.e. patients and parents). Conclusions The levels and factors of generic and transplant-specific HRQOL of Japanese pediatric and adolescent patients with BA after LDLT varied with reporter (i.e. patients or parents).

We report a case involving a rescued low birth weight infant (LBWI) with acute liver failure. Case: The patient was 1594 g and 323/7 gestational wk at birth. At the age of 11 d, she developed acute liver failure due to gestational alloimmune liver disease. Exchange transfusion and high-dose gamma globulin therapy were initiated, and body weight increased with enteral nutrition. Exchange transfusion was performed a total of 33 times prior to living donor liver transplantation (LDLT). Her liver dysfunction could not be treated by medications alone. At 55 d old and a body weight of 2946 g, she underwent LDLT using an S2 monosegment graft from her mother. Three years have passed with no reports of intellectual disability or liver dysfunction. LBWIs with acute liver failure may be rescued by LDLT after body weight has increased to over 2500 g.

This is the first report of living donor liver transplantation (LDLT) for congenital hepatic fibrosis (CHF) using a mother's graft with von Meyenburg complex. A 6-year-old girl with CHF, who suffered from recurrent gastrointestinal bleeding, was referred to our hospital for liver transplantation. Her 38-year-old mother was investigated as a living donor and multiple biliary hamartoma were seen on her computed tomography and magnetic resonance imaging scan. The mother's liver function tests were normal and she did not have any organ abnormality, including polycystic kidney disease. LDLT using the left lateral segment (LLS) graft from the donor was performed. The donor LLS graft weighed 250 g; the graft recipient weight ratio was 1.19%. The operation and post-operative course of the donor were uneventful and she was discharged on post-operative day (POD) 8. The graft liver function was good, and the recipient was discharged on POD 31. LDLT using a graft with von Meyenburg complex is safe and useful. Long-term follow-up is needed with respect to graft liver function and screening malignant tumors.

Background Health-related quality of life (HRQOL) is an important outcome in pediatric solid organ transplantation. Considering the emerging problems after transplantation, an evaluation of transplant-specific aspects of HRQOL is essential, but no validated HRQOL measure is available in Japan. The aim of this study was therefore to develop the Japanese version of the Pediatric Quality of Life Inventory™ (PedsQL) Transplant Module Child Self-Report and to investigate its feasibility, reliability, and validity. Methods Based on the PedsQL linguistic validation process, the Japanese version of the PedsQL Transplant Module was developed through translation and cognitive interviews (patient testing). The scale's reliability and validity were investigated, using statistical analyses of field tests of the target population. Results Eighty-seven pairs of pediatric liver-transplant recipients and their parents participated in the field test. The pediatric patients completed the measure in 3–7 min, and the rate of missing items was low (0.27%). Excellent internal consistency and test–retest reliability were confirmed. Known-groups validity, concurrent validity, and convergent and discriminant validity also were confirmed. Conclusions Excellent feasibility, reliability, and validity of this Japanese self-report version of the PedsQL Transplant Module Child Self-Report were verified. As a measure of transplant-specific aspects of HRQOL in Japanese pediatric patients who have undergone organ transplants, the Japanese version of the PedsQL Transplant Module is appropriate for use in clinical and research settings.

A temporary portocaval shunt (TPCS) associated with retrohepatic vena cava preservation prevents the edema caused by splanchnic congestion during liver transplantation (LT), especially for non-cirrhotic cases. We herein report a modified TPCS technique using the recanalized umbilical vein and an end-to-side recanalized umbilico-caval anastomosis for use during pediatric living donor liver transplantation (LDLT). This work evaluated a group of pediatric patients who underwent LDLT between 2001 and 2014 with the conventional TPCS (n=16) vs the recanalized umbilico-caval shunt (the crossed fingers method, n=10). The crossed fingers method was performed by suturing an end-to-side anastomosis of the patent or recanalized umbilical vein to the vena cava using a continuous monofilament suture like "crossing the fingers," that is, placing the left portal vein across the portal vein trunk next to it. The preoperative, surgical, and postoperative characteristics were similar in both groups except for the significantly shorter portal vein clamping time for the crossed fingers method. This method can allow the portal circulation to be totally decompressed before and after implanting the graft and while maintaining the hemodynamic stability throughout all stages of pediatric LDLT.

Advances in interventional radiology (IVR) treatment have notably improved the prognosis of hepatic vein (HV) and portal vein (PV) complications following pediatric living donor liver transplantation (LDLT); however, graft failure may develop in refractory cases. Although endovascular stent placement is considered for recurrent stenosis, its indications are controversial. We enrolled 282 patients who underwent pediatric LDLT in our department from May 2001 to September 2016. 22 (7.8%) HV complications occurred after LDLT. Recurrence was observed in 45.5% of the patients after the initial treatment, and 2 patients (9.1%) underwent endovascular stent placement. The stents were inserted at 8 months and 3.8 years following LDLT, respectively. After stent placement, both patients developed thrombotic obstruction and are currently being considered for re-transplantation. 40 (14.2%) PV complications occurred after LDLT. Recurrence occurred in 27.5% of the patients after the initial treatment, and 4 patients (10.0%) underwent endovascular stent treatment. The stents of all the patients remained patent, with an average patency duration of 41 months. Endovascular stent placement is an effective treatment for intractable PV complications following pediatric LDLT. However, endovascular stent placement for HV complications should be carefully performed because of the risk of intrastent thrombotic occlusion and the possibility of immunological venous injury.

Hepatic ischemia-reperfusion (I/R) injury is a major problem in liver transplantation (LT). Although hepatocyte cell death is the initial event in hepatic I/R injury, the underlying mechanism remains unclear. In the present study, we retrospectively analyzed the clinical data of 202 pediatric living donor LT and found that a high serum ferritin level, a marker of iron overload, of the donor is an independent risk factor for liver damage after LT. Since ferroptosis has been recently discovered as an iron-dependent cell death that is triggered by a loss of cellular redox homeostasis, we investigated the role of ferroptosis in a murine model of hepatic I/R injury, and found that liver damage, lipid peroxidation, and upregulation of the ferroptosis marker Ptgs2 were induced by I/R, and all of these manifestations were markedly prevented by the ferroptosis-specific inhibitor ferrostatin-1 (Fer-1) or α-tocopherol. Fer-1 also inhibited hepatic I/R-induced inflammatory responses. Furthermore, hepatic I/R injury was attenuated by iron chelation by deferoxamine and exacerbated by iron overload with a high iron diet. These findings demonstrate that iron overload is a novel risk factor for hepatic I/R injury in LT, and ferroptosis contributes to the pathogenesis of hepatic I/R injury.

Background We present a retrospective analysis of our experience with pediatric liver transplantation (LT), focusing on the long-term outcome of percutaneous transhepatic biliary drainage (PTBD) for post-transplant biliary strictures. Methods Fifty-three PTBDs were performed for 41 pediatric recipients with biliary strictures. The median ages at LT and PTBD were 1.4 and 4.4 years, respectively. The median observation period was 10.6 years. Results Post-transplant biliary strictures comprised anastomotic stricture (AS) in 28 cases, nonanastomotic stricture (NAS) in 12, anastomotic obstruction (AO) in 8, and nonanastomotic obstruction (NAO) in 5. The success rate of PTBD was 90.6%, and the 15-year primary patency rate of PTBD was 52.6%. The recurrence rate of biliary strictures after PTBD was 18.8% (9/48), and among the four NAS cases with recurrence, two underwent re-LT. The biliary obstruction rate was 27.1% (13/48). Among the eight cases with AO, five underwent the rendezvous method and three underwent surgical re-anastomosis. Among the five cases with NAO, one underwent re-LT. The recipient survival rate of PTBD treatment was 100%. Conclusions The graft prognosis of AS by PTBD treatment is good and AO is curable by the rendezvous method and surgical re-anastomosis. However, the graft prognosis of NAS and NAO is poor.

Background We present retrospective analysis of our 15-year experience with pediatric living donor liver transplantation, focusing on the risk factors, treatments, and long-term prognosis for posttransplant biliary complications (BCs). Methods Between May 2001 and December 2017, 290 living donor liver transplantations were performed. The median age was 1.4 years old. The median observation period was 8.4 years. Biliary strictures were classified as anastomotic stricture (AS) or non-AS (NAS). Results Overall incidence of biliary complications was 18.6%, including AS in 46 cases, NAS in 6, and other classifications in 2. The mean period to diagnosis of the AS was 641 ± 810 postoperative days. The multivariate analysis showed that hepaticojejunostomy without external stent was an independent risk factor for AS (P = 0.011). The first treatments for AS were percutaneous transhepatic biliary drainage (PTBD) in 25 cases, double-balloon enteroscopy (DBE) in 19, and surgical reanastomosis in 2. The success and recurrence rates of PTBD treatments were 90.9% and 22.7%, respectively. The success and recurrence rates of endoscopic interventions under DBE were 93.6% and 75.3%, respectively. The 15-year graft survival rates in patients with and without AS were 95.7% and 89.1%, respectively (P = 0.255), but 2 patients with cholangitis due to multiple NAS underwent retransplantation. Conclusions Posttransplant AS can be prevented by hepaticojejunostomy using external stent, and the long-term prognosis is good with early treatments using DBE or PTBD. However, the prognosis of multiple NAS is poor.

Utilizing the opened round ligament as venous grafts during liver transplantation is useful but controversial, and there are no pathological analyses of this procedure. Herein, we describe the first reported case of a pathological analysis of an opened round ligament used as a venous patch graft in a living donor liver transplantation (LDLT). A 13-year-old female patient with biliary atresia underwent LDLT using a posterior segment graft from her mother. The graft had two hepatic veins (HVs), which included the right HV (RHV; 15 mm) and the inferior RHV (IRHV; 20 mm). The graft RHV and IRHV were formed into a single orifice using the donor's opened round ligament (60 mm × 20 mm) as a patch graft during bench surgery; it was then anastomosed end-to-side with the recipient inferior vena cava. The recipient had no post-transplant complications involving the HVs, but she died of septic shock with persistent cholangitis and jaundice 86 d after LDLT. The HV anastomotic site had no stenosis or thrombus on autopsy. On pathology, there was adequate patency and continuity between the recipient's HV and the donor's opened round ligament. In addition, the stains for CD31 and CD34 on the inner membrane of the opened round ligament were positive. Hepatic venous reconstruction using the opened round ligament as a venous patch graft is effective in LDLT, as observed on pathology.

When living donor liver transplantation (LDLT) is performed on small infant patients, the incidence of hepatic artery complications (HACs) is high. Here, we present a retrospective analysis that focuses on our surgical procedure for hepatic arterial reconstruction and the outcomes of monosegmental LDLT. Of the 275 patients who underwent LDLT between May 2001 and December 2015, 13 patients (4.7 %) underwent monosegmental LDLT. Hepatic artery reconstruction was performed under a microscope. The size discrepancy between the graft and the recipient’s abdominal cavity was defined as the graft to recipient distance ratio (GRDR) between the left hepatic vein and the portal vein (PV) bifurcation on a preoperative computed tomography scan. HACs were defined as hepatic arterial hypoperfusion. Recipient hepatic arteries were selected for the branch patch technique in five cases (38.5 %), and the diameter was 2.2 ± 0.6 mm. The anastomotic approaches selected were the dorsal position of the PV in seven cases (53.8 %) and the ventral position in six, and the GRDRs were 2.8 ± 0.4 and 1.9 ± 0.5, respectively (p = 0.012). The incidence rate of HACs caused by external factors, such as compression or inflammation around the anastomotic site, was significantly higher in monosegmental than in non-monosegmental graft recipients (15.4 vs. 1.1 %, p

The safety and efficacy of double-balloon enteroscopy (DBE) in pediatric patients has not been well documented. We aimed to evaluate the clinical efficacy and safety of DBE in children, especially those under 10.We retrospectively analyzed our database of DBE procedures performed between September 2000 and September 2013. Procedures performed in pediatric patients (under 18) were selected from a total of 3980, including double-balloon endoscopic retrograde cholangioscopy (DBERC).Two hundred fifty-seven DBE procedures were performed in 117 pediatric patients (median age 12.5 years). Antegrade (oral-route) DBE was performed in 166 procedures including 104 DBERC procedures (lowest body weight 13.5 kg, youngest age 3 years), and retrograde (anal-route) DBE in 91 (lowest body weight 12.0 kg, youngest age 2 years). The overall diagnostic yield for obscure gastrointestinal bleeding and abdominal pain was 58.8%. The purpose of DBERC was achieved in 76.9% of procedures. The overall complication rate in our series was 5.4% (1.9% with the DBERC cases removed); in patients under 10, it was 10.4% (7/67). No severe complications associated with enteroscope insertion and sedation were observed. Serum amylase levels tended to be elevated in patients who underwent oral-route DBE.DBE is safe and feasible for diagnostic evaluation of small bowel disorders in pediatric patients, even those younger than 10 years. Special attention for possible complications must, however, be paid during therapeutic DBE procedures, including DBERC, especially for patients under 10.

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.

Background In small infants, left lateral segment grafts are sometimes too large to overcome the problems of large-for-size grafts in the abdominal compartment. To address this problem, we have developed a safe living donor graftectomy for neonates, a so-called “S2 monosegment graft” to minimize graft thickness. We reviewed our single-center experience to evaluate the feasibility of this technique for reducing graft size. Methods Eleven living-donor liver transplants using S2 monosegment grafts were performed between October 2008 and September 2014 at our institution. Medical records of both donors and recipients were reviewed and data collected retrospectively. Results The mean age of recipients at the time of transplantation was 125.3 days, including 3 neonates. The average S2 monosegment graft weight was 127.4 g, and the graft-to-recipient body weight ratio was successfully reduced to 3.5%. The graft livers were reduced to 4.1 cm in thickness. Two recipients with grafts larger than 5 cm could not undergo primary abdominal closure. Portal vein stenosis and biliary stenosis was observed in 1 recipient, and hepatic artery complications were seen in 2 recipients; the clinical course for all donors were uneventful. Liver regeneration was seen in every patient. The graft and patient 1-year survival rate was 100%. Conclusions Living-donor liver transplantation using S2 monosegment grafts offers a safe and useful option for treating smaller infants. Here, we introduce our method of S2 monosegment graft emphasizing the donor harvest and graft thickness.

Background Although there have been a few reports describing the changes of graft liver and spleen volumes after liver transplantation (LT), little is known about the relationship between graft liver function and the changes of these volumes after technical variant liver transplantation (TVLT). We therefore performed a retrospective study to investigate the relationship between graft liver function and these volumes after TVLT. Methods We retrospectively investigated the cases of 140 TVLT procedures that were performed in our department between July 1987 and October 2012 and in which follow-up was conducted at our department. We calculated the graft liver volume to standard liver volume (GV/SLV) ratio, the spleen volume to standard spleen volume (SV/SSV) ratio, and the spleen volume to graft liver volume (S/L) ratio by CT volumetry. We clarified the relationship between graft liver function (according to the pathological findings) and the graft liver and spleen volumes at 2, 5, and 10 years after TVLT. Results In the normal liver function group, the GV/SLV, SV/SSV, and S/L ratios decreased until 6 months after TVLT and then converged at 10 years after TVLT to 0.95, 1.27, and 0.27, respectively. In the graft liver failure group, the GV/SLV, SV/SSV, and S/L ratios at 10 years after TVLT were 0.67, 5.01, and 1.55, respectively. A significant correlation was observed between the GV/SLV ratio and the presence of mild liver fibrosis at 2 and 5 years after TVLT ( P = .03 and P = .04, respectively). Conclusions Post-transplant CT-volumetry is a noninvasive and effective means of evaluating graft liver status.

We aimed to evaluate patients who had undergone pediatric LDLT with small-for-size graft (SFSG) and identify risk factors of graft failure to establish a preoperative graft selection strategy. The data was collected retrospectively. SFSG was used in 14LDLTs (5.7 %) of 245 LDLTs performed between May 2001 and March 2014. The mean patient age and body weight at LDLT were 12.6 ± 2.0 years and 40.5 ± 9.9 kg, respectively. The graft type was left lobe in six patients, left + caudate lobe in seven patients, and posterior segment in one patient. The graft survival rates in SFSG and non-SFSG groups were 78.9 and 93.1 %, respectively (p = 0.045). In the univariate analysis, bleeding volume during LDLT were an independent risk factors for graft failure (p = 0.011). Graft failure was caused by sepsis in all three patients and occurred at a median of 70 postoperative days 70 (range 14–88 days). Among them, two cases showed high preoperative PELD/MELD score (PELD; 19.4 and MELD; 22, respectively). Pediatric LDLT using SFSG had poor outcome and prognosis, especially when it accompanies the surgical infectious complications with preoperative high PELD/MELD scores.

The serum ferritin (SF) concentration is a widely available and objective laboratory parameter. SF is also widely recognized as an acute-phase reactant. The purpose of the present study was to identify the chronological changes in the recipient's SF concentration during liver transplantation (LT) and to clarify factors having an effect on the recipient's intraoperative SF level. In addition, the study retrospectively evaluated the usefulness of measuring SF during LT. Ninety-eight pediatric recipients were retrospectively analyzed. The data were analyzed and compared according to the SF level in the recipient. Patients were classified into 2 groups based on the intraoperative peak SF levels of ≤ 1000 ng/mL (low-SF group) or >1000 ng/mL (high-SF group). The SF value increased dramatically after reperfusion and fell to normal levels within the early postoperative period. The warm ischemia time (WIT) was significantly longer in the high-SF group (47.0 versus 58.5 minutes; P = 0.003). In addition, a significant positive correlation was observed between the peak SF value and WIT (r = 0.35; P < 0.001). There were significant positive correlations between the peak SF value and the donors' preoperative laboratory data, including transaminases, cholinesterase, hemoglobin, transferrin saturation, and SF, of which SF showed the strongest positive correlation (r = 0.74; P < 0.001). The multivariate analysis revealed that WIT and donor's SF level were a significant risk factor for high SF level in the recipient (P = 0.007 and 0.02, respectively). In conclusion, the SF measurement can suggest the degree of ischemia/reperfusion injury (IRI). A high SF level in the donor is associated with the risk of further acute reactions, such as IRI, in the recipient.

Adverse event A drug interaction leading to greater exposure to tacrolimus. Drug implicated Tacrolimus and Beni-Madonna (a new cultivar citrus categorized as 'Tangor'). The patient A 9-month-old girl with biliary atresia (body weight, 7.5 kg) taking tacrolimus after liver transplantation. Evidence that links the drug to the event The time course was consistent with the appearance of the interaction, which was confirmed by an increase in the blood concentration of tacrolimus. Dihydroxybergamottin was detected in peel of Beni-Madonna and in peel and fruit pulp of grapefruit. Management Avoiding Beni-Madonna intake. Mechanism Inhibition of activity of CYP3A4, P-glycoprotein, or both, by Beni-Madonna. Implication for therapy Clinicians should be aware of this potential interaction, and patients taking drugs such as tacrolimus (the kinetics of which are affected by grapefruit juice) should avoid Beni-Madonna intake. Hypothesis to be tested Further study is required to determine if other Citrus species categorized as Tangor contain furanocoumarins.

Niemann-Pick disease type C (NPC) is a rare autosomal recessive inherited disease characterized by lysosomal accumulation of free cholesterol in macrophages within multiple organs. Infantile-onset NPC often presents with jaundice and hepatosplenomegaly from birth, but these symptoms usually improve during early childhood, and it rarely progresses to liver failure. We report three cases from different hospitals in Japan; the patients developed neonatal-onset NPC, and liver transplantation (LT) was performed as a life-saving procedure. LT was performed at 19 days, 59 days, and 4 months of age, respectively. The last patient was diagnosed with NPC before LT, while the first two patients were diagnosed with neonatal hemochromatosis at LT. In these two patients, the diagnosis of NPC was made more than a year after LT. Even though oral administration of miglustat was started soon after the diagnosis of NPC, all patients showed neurological regression and required artificial respiratory support. All patients survived more than one year after LT; however, one patient died due to tracheal hemorrhage at 4.5 years of age, and another one patient was suspected as recurrence of NPC in liver graft. In conclusion, while LT may be a temporary life-saving measure in patients with neonatal-onset NPC leading to liver failure, the outcome is poor especially due to neurological symptoms. A preoperative diagnosis is thus critical.

Congenital portosystemic shunt (CPS) is classified into type I (congenital absence of the portal vein) and type II, depending on the presence or absence of the intrahepatic portal vein. Reports still exist on cases in which psychiatric diseases or mental retardation was diagnosed or cases in which diagnosis and treatment are not performed until severe pulmonary complications occur, indicating the need to recognize CPS. Herein, we reviewed epidemiology, etiology, classification, symptom, diagnosis, and treatment based on clinical view points of CPS. For clinical view points, classification according to (1) the presence or absence of the intrahepatic portal venous system (IPVS) and (2) the extrahepatic or intrahepatic of shunt sites, facilitates the understanding of pathophysiological conditions and is useful in selecting a treatment for symptomatic CPS. Radiological and pathological examinations are important in IPVS evaluations, and IPVS evaluations are currently essential to make diagnoses by portography with balloon occlusion and liver biopsy. Symptomatic CPS (hepatic nodular lesions, portosystemic encephalopathy, and pulmonary complications, etc.) is an indication of treatment by shunt closure, but an indication of treatment for asymptomatic CPS is the challenge going forward.

There are few long-term outcome reports for interventional radiology (IVR) treatments for vascular and biliary complications following pediatric living donor liver transplantation (LDLT). Herein, we presented our institution's experience and investigated the efficacy and issues of long-term outcome with IVR treatments. Between May 2001 and September 2016, 279 pediatric LDLTs were performed. The median age at LDLT was 1.4 years old, and the median observation period was 8.2 years. All the biliary reconstructions at LDLT were hepaticojejunostomy. The IVR treatments were selected as endovascular, radiological, or endoscopic interventions. Post-transplant hepatic vein, portal vein, hepatic artery, and biliary complications were present in 7.9%, 14.0%, 5.4%, and 18.3%, respectively. IVR treatment was the first treatment option in 81.8%, 94.9%, 46.7%, and 94.1%, respectively. The recurrence and cure rates following IVR treatment were 42.1%, 21.1%, 44.4%, and 34.0% and 84.2%, 97.4%, 100%, and 88.0%, respectively. The graft survival rates in patients with and without post-transplant vascular and biliary complications were 94.4% and 90.6%, respectively (P = 0.522). The IVR treatments for vascular and biliary complications following pediatric LDLT are the first choice option. Although the recurrence following IVR treatment is a major problem and it is necessary to carefully perform long-term follow-up, IVR treatments have good treatment outcomes.

Serum Mac-2 binding protein glycosylation isomer (M2BPGi) is a novel fibrosis marker for various chronic liver diseases. We investigated the ability of M2BPGi to predict liver fibrosis in liver transplant (LT) recipients.A total of 116 liver biopsies were performed in 113 LT recipients. The serum level of M2BPGi was also measured on the same day. The median age at LT and liver biopsy was 1.1 and 11.8 years, respectively. Serum M2BPGi levels and liver fibrosis status using METAVIR fibrosis score were compared. Immunohistological evaluation by anti-α-smooth-muscle actin (αSMA) was performed, and the relationship between αSMA positive rate and serum M2BPGi levels was investigated.The median M2BPGi level was 0.78 (range, 0.22-9.50), and 65, 29, 16, 5, and 1 patient(s) had METAVIR fibrosis scores of F0, F1, F2, F3, and F4, respectively. In patients with F0 fibrosis, median M2BPGi level was 0.69 and was significantly lower than in patients with F1 (median 0.99, P 0.01), F2 (median 1.00, P = 0.01), and F3 fibrosis (median 1.53, P 0.01). Area-under-the-curve analysis of the ability of M2BPGi level to predict liver fibrosis grade were F1: 0.716, F2: 0.720, and F3: 0.900. Three patients with acute cellular rejection showed high levels of M2BPGi, which decreased after the treatment. A positive correlation existed between M2BPGi levels and αSMA positive rate (rMac-2 binding protein glycosylation isomer is a novel liver fibrosis marker in LT recipients and is also increased in patients with acute liver injuries, especially acute cellular rejection, even when fibrosis is absent.

Purpose We reviewed our post-Kasai portoenterostomy biliary atresia (BA) patients who required liver transplantation (LTx) for deterioration in native liver (NL) function to investigate mortality in relation to age at LTx. Methods BA patients indicated for LTx when less than 18years old (U18; n=17) and when 18 or older (18+; n=13) were compared. All achieved jaundice clearance postoperatively (TBil ≤1.2mg/dL (≈20μmol/L)). Results In U18, living-donor (LD) LTxs were performed at a median of 6.1years (range: 0.5–16.7; n=14) and cadaveric (CD) LTxs at a median of 1.3years (1.1–1.5; n=3). In 18+, LDLTxs were performed at a median of 28years (18–37; n=8), and 1 case died from graft versus host disease. CDLTxs were indicated in 5, but 4 died at a median of 30years (26–32), a mean of 1.4years (0.7–1.8) after NL deterioration commenced. One case is awaiting CDLTx. At the time of review, all U18 and 7 LDLTx cases in 18+ were clinically stable. Mortality rates were 0% in U18 and 38% in 18+ (P=.006). Conclusion Our results highlight the extremely grave prognosis for long-term BA patients requiring LTx when 18 or older because of poor donor availability in Japan. Level of evidence Level III.

Background Hepatocellular nodules caused by congenital extrahepatic portosystemic shunts (CEPS) occur as a result of abnormal portal blood flow, and are mostly cases of benign focal nodular hyperplasia (FNH). However, hepatocellular adenomas (HCA) and hepatocellular carcinomas have been documented in the CEPS patients. HCA can now be immunohistochemically diagnosed; therefore, the concept of hepatocellular nodules resulting from CEPS should be revisited. In this study, we performed a retrospective immunohistochemical investigation of hepatocellular nodules from livers isolated from the CEPS patients undergoing living donor liver transplantation (LDLT). Methods Hepatocellular nodules from livers of five patients with CEPS who underwent LDLT between June 2004 and October 2012 at our institution were immunohistochemically investigated. HCA were classified into four subtypes (HNF1α-inactivated HCA (H-HCA); inflammatory HCA; β-catenin-activated HCA (b-HCA); unclassified HCA). Results Sixteen hepatocellular nodules were collected from livers of five patients with CEPS who underwent LDLT. Ten hepatocellular nodules were categorized as FNH (62.5%), five were categorized as b-HCA (31.3%), and one was categorized as H-HCA (6.2%). Conclusions Some of the hepatocellular nodules resulting from CEPS were indicative of HCAs, especially the b-HCA subtype which has the potential for malignant transformation. Surgical or interventional treatments might have to be performed when hepatocellular nodules appear in the CEPS patients.

Studies suggest that prophylactic intra-abdominal drains are unnecessary for cadaveric liver transplantation using whole liver grafts because there is no benefit from drainage. However, no studies have investigated on the necessity of prophylactic drains after LDLT using split-liver grafts or reduced-liver grafts, which may present a high risk of post-transplant intra-abdominal infections. This retrospective study investigated whether the ascitic data on POD 5 after LDLT can predict intra-abdominal infections and on the post-transplant management of prophylactic drains. Between March 2008 and March 2013, 90 LDLTs were performed. We assessed the number of ascitic cells, biochemical examinations, and cultivation tests at POD1 and POD5. The incidence rates of post-transplant intra-abdominal infections were 24.4%. The multivariate analysis showed that left lobe and S2 monosegment grafts were a significant risk factor for intra-abdominal infections (p = 0.006). The patients with intra-abdominal infections had significantly higher acsitic LDH levels and the positive rate of ascitic culture at POD5 in comparison with patients without infections (p < 0.001 and p = 0.014, respectively). LDLT using left lobe and S2 monosegment grafts yields a high risk for post-transplant intra-abdominal infections, and ascitic LDH and cultivation tests at POD5 via prophylactic drains can predict intra-abdominal infections.

Background A merit of subnormothermic perfusion has been reported to preserve grafts from ischemic injury in animal models. The split liver technique is commonly performed to solve the shortage of liver grafts. However, there has been no study showing the effect of a split liver graft on subnormothermic perfusion. We herein investigated the split liver protocol using a subnormothermic oxygenated circuit system (SOCS). Methods Auxiliary liver transplantation was performed in a porcine marginal donor model by using a SOCS. In the SOCS group, the portal vein and hepatic artery of the graft were cannulated, and the graft was perfused by SOCS. In the cold storage (CS) group, the graft was placed in cold preservation solution. In the preservation phase, the graft was split. Results There were no significant differences in the biochemical markers between the SOCS and CS groups. In terms of the histology, the sinusoidal spaces were widened in the CS group 12 hours after implantation. Conclusion We have demonstrated a possibility to use SOCS with the split liver protocol by using a porcine model. This split liver protocol using SOCS will extend the split liver criteria and rescue more patients from hepatic failure, including pediatric patients.

Few studies have examined HRQOL in pediatric Tx recipients' parents. This study investigated HRQOL in these parents and relationships between HRQOL and perceived burden of nurturing, family functioning, and social support. Self-report anonymous questionnaires and a survey of medical records were completed between September and December 2013. The SF-36v2, which evaluates physical, psychological, and social health, was used to measure HRQOL. While values for physical and psychological health were higher than standard values (Cohen's d = 0.34 and 0.17, respectively), social health scores were lower (d = 0.21). "Parental consultation unrelated to donation" (standardized partial regression coefficient: β = -0.52) was associated with physical health. "Family functioning" and "Commuting time between home and primary follow-up hospital" (β = 0.57 and -0.31) were related to psychological health. "Total score for perceived burden of nurturing" (β = -0.31) was related to social health. Regarding parental HRQOL, while physical and psychological health was favorable, social health was impaired. In clinical practice, interventions targeting parents' physical conditions and facilitation of community and family understanding and support to share recipients' nurturing are important in improving parental HRQOL.