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There is no consensus about long-term outcomes in patients with biliary atresia. We retrospectively reviewed the long-term outcomes in pediatric patients who underwent living donor liver transplantation for biliary atresia.Between May 2001 and December 2020, 221 (73%) of 302 pediatric patients who underwent living donor liver transplantation had biliary atresia. The median age at living donor liver transplantation was 1.2 (range 0.2-16.5) years, and follow-up was 10.3 ± 5.5 years.The 10-year graft survival rates in patients with and without biliary atresia were 94% and 89%, respectively (P = .019). The 10-year graft survival was significantly poorer in patients ≥12 years of age (84%) versus those12 years of age at living donor liver transplantation (0-2 years: 95%; 2-12 years: 96%) (P = .016). The causes of graft failure in patients with biliary atresia included late-onset refractory rejection (n = 6), bowel perforation (n = 2), and acute encephalitis (n = 2), as well as cerebral hemorrhage, hepatic vein thrombosis, and sepsis (n = 1 for all). All 7 patients with graft failure due to refractory rejection and hepatic vein thrombosis underwent repeated liver transplantation and are alive in 2021. The rates of post-transplant portal vein complications and early-onset acute cellular rejection in patients with biliary atresia were higher than in those without biliary atresia (P = .042 and P = .022, respectively). In 2021, of 60 adolescents with biliary atresia, 14 (23%) reported medication nonadherence. The rate of liver dysfunction due to late-onset acute cellular rejection and graft failure due to late-onset refractory rejection in patients with nonadherence was higher than in patients with satisfactory adherence (P = .009).The long-term prognosis after living donor liver transplantation in pediatric patients with biliary atresia is quite good. However, long-term support to enhance medication adherence is required in adolescents with biliary atresia.

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.

Background Myotubular myopathy is a rare disease sometimes accompanied by peliosis hepatis, a leading cause of fatal liver hemorrhage. Case Report We present a case of a 2-year-old boy with myotubular myopathy who developed liver hemorrhage because of peliosis hepatis and was successfully treated with living-donor liver transplant. The patient initially presented with fever, anemia, and liver dysfunction. A computed tomographic scan revealed hemorrhages in the liver, and the patient underwent hepatic artery embolization twice. After the second embolization, multiple peliosis hepatis cavities appeared in the left lobe of the liver that had increased in size. Therefore, the patient underwent ABO-incompatible living-donor liver transplant using a lateral segment graft from his father. The patient developed severe septic shock with an unknown focus on postoperative day 18, which resolved with antibiotic therapy. On postoperative day 62, he was discharged. Fourteen months after undergoing living-donor liver transplant, the patient showed no recurrence of peliosis hepatis. Conclusions Although the long-term prognosis of peliosis hepatis due to myotubular myopathy after living-donor liver transplant remains unclear, liver transplant may be a curative treatment for patients with myotubular myopathy who have uncontrollable peliosis hepatis.

Background This study aimed to describe our experience with three-dimensional endoanal ultrasonography (3D-EAUS) in patients who underwent surgery for Hirschsprung disease and to summarize the relationship between postoperative anal function and the distance between the anastomosis and intersphincteric groove (DBAI) measured via 3D-EAUS. Results We retrospectively reviewed patients with a history of undergoing surgery for Hirschsprung disease who visited our outpatient clinic between December 2018 and December 2019. All patients underwent 3D-EAUS for DBAI measurement. We used the Krickenbeck classification to evaluate postoperative anorectal function. Eleven patients (all males aged 3–14 years) were evaluated. Four (36.4%), four (36.4%), and three (27.3%) patients had no soiling, grade 1 soiling, and grade 3 soiling, respectively. Four (36.4%) and seven (63.6%) patients had no constipation and grade 3 constipation, respectively. The median DBAI values were 7.0 mm, 8.4 mm, and 5.6 mm (p = 0.14) in the no soiling, grade 1, and grade 3 soiling groups, respectively. Conclusions 3D-EAUS enabled precise visualization of the anal anatomy and evaluation of the anastomosis. The DBAI was relatively short in patients with grade 3 soiling, although not significantly so. Further evaluation is warranted.

Sinusoidal obstruction syndrome (SOS) after liver transplantation (LT) is a rare and potentially lethal complication. We retrospectively reviewed the outcomes of patients with post-transplant SOS.Between May 2001 and December 2019, of 332 patients who underwent LT, 5 (1.5%) developed SOS. The median age at LT was 1.7 years (range 0.1-66.5). SOS was histopathologically diagnosed and classified as early-onset (1 month) or late-onset.The median time to diagnosis of SOS was one month after LT. All patients developed acute cellular rejection before SOS, and the cause of SOS was acute cellular rejection in four patients and unknown in one. The treatment of SOS included conversion to tacrolimus from cyclosporine, intrahepatic hepatic vein stent placement, strengthening of immunosuppression, and plasma exchange. The 5-year graft survival rates in patients with and without SOS were 53.0% and 92.5%, respectively (p 0.001). Of three patients with early-onset SOS, two patients improved and are doing well, and one patient died of graft failure four months after LT.The cause and treatment of post-transplant SOS are not yet defined. The poor outcomes in patients with early-onset SOS may be improved by strengthening of immunosuppression. Patients with late-onset SOS are ultimately treated by repeat LT.

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.

Patients with hepatitis-associated aplastic anemia (HAA) who undergo living-donor liver transplantation (LDLT) have a poor prognosis with infections and bleeding complications. Rapid recovery of blood cells is critical for preventing these complications and improving the outcome. Immunosuppressive therapy (IST) combined with thrombopoietin receptor agonists is considered effective for aplastic anemia. However, there are no data on the benefits of adding thrombopoietin receptor agonists to IST for HAA. We present the case of a child with severe HAA who underwent LDLT, and who achieved rapid blood cell recovery with IST combined with romiplostim, a thrombopoietin receptor agonist. In addition, despite having undergone LDLT, the patient had no adverse events such as serious liver dysfunction or thrombosis. This case suggests that IST combined with thrombopoietin receptor agonists may be a promising treatment option for HAA patients undergoing LDLT.

Objectives Predicting the risk of posthepatectomy liver failure is important when performing extended hepatectomy. However, there is no established method to evaluate liver function and improve preoperative liver function in pediatric patients. Materials and methods We show the clinical features of pediatric patients who underwent living donor liver transplant for posthepatectomy liver failure in hepatoblastoma. The subjects were 4 patients with hepatoblastoma who were classified as Pretreatment Extent of Disease III, 2 of whom had distal metastasis (chest wall and lung). Results Hepatic right trisegmentectomy was performed in 3 patients and extended left hepatectomy in 1 patient. The median alpha-fetoprotein level at the diagnosis of hepatoblastoma was 986300 ng/mL (range, 22500-2726350 ng/mL), and the median alpha-fetoprotein level before hepatectomy was 8489 ng/mL (range, 23-22500 ng/mL). The remnant liver volume after hepatectomy was 33.3% (range, 20% to 34.9%). Four patients had cholangitis after hepatectomy and progressed to posthepatectomy liver failure. The peak serum total bilirubin after hepatectomy was 11.4 mg/dL (range, 8.7-14.6 mg/dL). Living donor liver transplant was performed for these 4 patients with posthepatectomy liver failure, and they did not have a recurrence. Conclusions When the predictive remnant liver volume by computed tomography-volumetry before extended hepatectomy for patients with hepatoblastoma is less than 40%, the possibility of posthepatectomy liver failure should be recognized.

Background There have been no reports on the effectiveness of the administration of antithrombin III (AT III) for post-transplant portal vein thrombosis (PVT). We herein report a case of post-transplant PVT that was resolved by AT III treatment after living donor liver transplantation (LDLT). Case presentation The patient was a 57-year-old man who had been diagnosed with decompensate liver cirrhosis by hepatitis C virus infection. He presented with repeated hepatic coma and refractory ascites. Computed tomography (CT) revealed PVT of Yerdel classification grade II before LDLT. He underwent ABO-identical LDLT using a right lobe graft. A liver function test revealed elevated liver enzyme levels on post-operative day (POD) 14. The CT examination on POD 15 revealed PVT in the left side of the main portal vein at the side of left gastric vein ligation. AT III treatment from POD 15 to POD 24 was performed. Magnetic resonance imaging revealed that the PVT had decreased 10% on POD 27. Furthermore, AT III treatment from POD 28 to POD 32 was performed. The CT examination demonstrated the disappearance of PVT on POD 69 and thereafter, he had no recurrence of PVT on 10 post-operative month (POM). Conclusions The present case suggests that the administration of AT III is safe and suitable for the treatment of post-transplant PVT.

BACKGROUND The number of pregnancies after liver transplantation (LT) is increasing; however, the safety and incidence of complications associated with these pregnancies are still unclear. In this report, we retrospectively assessed the influences and problems associated with post-transplant pregnancy on allografts, recipients, and fetuses. MATERIAL AND METHODS A total of 14 pregnancies were identified in 8 female recipients between 2005 and 2018. The original disease was biliary atresia in all recipients. We provide a basic guide for the management of planned pregnancies in female recipients. RESULTS Of the 7 planned pregnancies, no recipients took mycophenolate mofetil (MMF) or had allograft liver dysfunction. Among the 7 unplanned conceptions, we judged that the pregnancy was inadequate to continue in 4 recipients due to taking MMF and 2 recipients due to allograft liver dysfunction at conception. However, 4 recipients who immediately stopped taking MMF continued with their pregnancies. Ten pregnancies resulted in live 11 births. Among obstetric complications or fetal and neonatal complications, gestational diabetes mellitus in 3 recipients was the most common. There were 3 miscarriages and 1 planned termination because of MMF medication and liver dysfunction. CONCLUSIONS Planned pregnancies in LT recipients can lead to the birth of a healthy baby and no influence on either the allograft or the recipient. However, unplanned pregnancies in LT recipients, such as recipients who take MMF or have allograft liver dysfunction, may have an adverse influence on the fetus.

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.

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

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.

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.

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.

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.

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

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.

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.

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.

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.

In the field of pediatric living donor liver transplantation (LDLT), physicians sometimes must reduce the volume of left lateral segment (LLS) grafts to prevent large-for-size syndrome. There are 2 established methods for decreasing the size of an LLS graft: the use of a segment 2 (S2) monosegment graft and the use of a reduced LLS graft. However, no procedure for selecting the proper graft type has been established. In this study, we conducted a retrospective investigation of LDLT and examined the strategy of graft selection for patients weighing ≤6 kg. LDLT was conducted 225 times between May 2001 and December 2012, and 15 of the procedures were performed in patients weighing ≤6 kg. We selected S2 monosegment grafts and reduced LLS grafts if the preoperative computed tomography (CT)-volumetry value of the LLS graft was >5% and 4% to 5% of the graft/recipient weight ratio, respectively. We used LLS grafts in 7 recipients, S2 monosegment grafts in 4 recipients, reduced S2 monosegment grafts in 3 recipients, and a reduced LLS graft in 1 recipient. The reduction rate of S2 monosegment grafts for use as LLS grafts was 48.3%. The overall recipient and graft survival rates were both 93.3%, and 1 patient died of a brain hemorrhage. Major surgical complications included hepatic artery thrombosis in 2 recipients, bilioenteric anastomotic strictures in 2 recipients, and portal vein thrombosis in 1 recipient. In conclusion, our graft selection strategy based on preoperative CT-volumetry is highly useful in patients weighing ≤6 kg. S2 monosegment grafts are effective and safe in very small infants particularly neonates.

Neonatal hemochromatosis (NH) is a rare disease with a poor prognosis, particularly prior to 2008. Antenatal maternal high-dose immunoglobulin (Ig) is effective in preventing NH recurrence, but the adverse effects of this treatment have not been documented as yet. Here, we report on a patient who underwent high-dose Ig treatment to prevent NH recurrence. The patient was a 31-year-old pregnant Japanese woman. Her first child died of NH after receiving living donor liver transplantation. The patient received high-dose Ig treatment to prevent recurrence of NH from gestational weeks 16 to 35. During the treatment, platelet count gradually decreased, and cesarean section was required at 35 gestational weeks. The child did not develop liver failure. High-dose Ig prevented the recurrence of NH. Caution should be exercised due to possible adverse effects of this treatment.

Background Antibody drugs have been used to treat steroid-resistant rejection (SRR) after liver transplantation. Although anti-thymocyte globulin has been used for SRR after liver transplantation in place of muromonab-CD3 since 2011 in Japan, the effectiveness of anti-thymocyte globulin after pediatric living-donor liver transplantation (LDLT) has not yet been reported. The aim of this study was to evaluate the effectiveness of antibody drug treatment for SRR after pediatric LDLT in our single center. Methods Between May 2001 and December 2013, 220 pediatric LDLTs were performed. Initial immunosuppression after LDLT included tacrolimus and methylprednisolone therapy. Acute rejection was diagnosed by use of a liver biopsy and the administration of steroid pulse treatment, and SRR was defined as acute rejection refractory to the steroid pulse treatment. Results Acute rejection and SRR occurred in 74 (33.6%) and 16 patients (7.3%), respectively. The graft survival rates of non-SRR and SRR were 92.4% and 87.5%, respectively (P = .464). The median concentration of alanine aminotransferase before and after the administration of antibody drug was 193.5 mU/mL (range, 8–508) and 78 mU/mL (range, 9–655), respectively (P = .012). The median rejection activity index before and after the administration of antibody drugs was 5 (range, 2–9) and 1 (range, 0–9), respectively (P = .004). After antibody drug treatment, 12 patients had cytomegalovirus infections, 2 patients had Epstein-Barr virus infections, 3 patients had respiratory infections, and 1 patient had encephalitis. The cause of death in 1 patient with SRR was recurrence of infant fulminant hepatic failure. Conclusions Antibody drug treatment for SRR after pediatric LDLT is safe and effective.

Background The hepatic clearance of endotoxin (Et) may reflect hepatic functional reserve and ischemic injury to hepatocytes. Therefore, we examined the relationships between Et activity (EA) and the metrics Pediatric End-Stage Liver Disease (PELD)/Model of End-Stage Liver Disease (MELD) score and alanine transaminase (ALT) levels in the postoperative period. Methods We performed 8 living-donor liver transplantations (LDLTs) for biliary atresia at our center from April 2012 to December 2012. EA was measured by means of an Et activity assay (EAA) in samples collected from a vein 1 day before LDLT, from the portal vein during the intraoperative anhepatic phase, from an artery 1 hour after reperfusion, from an artery on postoperative day (POD) 1, and from an artery or vein at PODs 7 and 14. Results EAs generally remained at low levels. EA at the reperfusion period was significantly lowest. The correlation coefficient for the preoperative MELD/PELD score and the EAA was 0.837, and the corresponding P value was .009; thus, there was a significant relationship between the preoperative MELD/PELD score and the EAA. The correlation coefficients for ALT at POD 1 and EA during the anhepatic phase, at 1 hour after reperfusion, and at POD 1 were 0.64, 0.43, and 0.38, respectively, and the P values for these correlations were .08, .67, and .34. Thus, we observed that ALT and EA generally tended to be somewhat directly correlated, but no significant relationships between these 2 metrics were observed. Conclusions Endotoxin metabolism reflects the hepatic functional reserve capacity of end-stage liver disease.

BACKGROUND Intracranial and pulmonary vascular anomalies are well-known complications and causes of mortality in AGS; however, visceral artery anomalies are less commonly recognized. Herein, we present a retrospective analysis of our experience with pediatric LDLT that focuses on the current problems with and treatments for visceral artery anomalies in AGS after LDLT. METHODS Between May 2001 and December 2017, 294 LDLTs were performed for 285 pediatric recipients. Of these, 13 LDLTs (4.4%) for 12 AGS patients were performed. We classified the visceral artery anomalies into aneurysms and stenosis. RESULTS The overall incidence of visceral aneurysm was 2 of 12 recipients (16.7%) and included a SMA aneurysm in one patient and an IPDA aneurysm with a subsequent SPA aneurysm in one patient; the ages of the diagnosis of visceral aneurysm were 16.3, 21.1, and 21.7 y, respectively. An endovascular treatment was performed for a progressive IPDA saccular aneurysm (12.0 × 14.5 × 15.0 mm). The overall incidence of visceral artery stenosis was 7 of 12 recipients (58.3%) and the median age at the diagnosis of visceral artery stenosis was 15.5 y (range 1.7-22.9 y). All 3 AGS patients with RA stenosis suffered from renal dysfunction (eGFR of 51, 78, and 51 mL/min/1.73m2 ). CONCLUSION The morbidity of visceral artery anomalies is not negligible. The performance of periodic imaging examinations is necessary, even for infants, because it is difficult to detect visceral vascular anomalies in the infant stage.

Mac-2 Binding Protein Glycosylation Isomer (M2BPGi) is a novel fibrosis marker. We examined the ability of M2BPGi to predict liver fibrosis in patients with biliary atresia. Sixty-four patients who underwent living donor liver transplantation (LDLT) were included [median age, 1.1 years (range 0.4–16.0), male 16 patients (25.0 %)]. We examined M2BPGi levels in serum obtained the day before LDLT, and we compared the value of the preoperative M2BPGi levels with the histological evaluation of fibrosis using the METAVIR fibrosis score. Subsequently, we assessed the ability of M2BPGi levels to predict fibrosis. The median M2BPGi level in patients with BA was 6.02 (range, 0.36–20.0), and 0, 1, 1, 11, and 51 patients had METAVIR fibrosis scores of F0, F1, F2, F3, and F4, respectively. In patients with F4 fibrosis, the median M2BPGi level was 6.88 (quartile; 5.235, 12.10), significantly higher than that in patients with F3 fibrosis who had a median level of 2.42 (quartile; 1.93, 2.895, p

Previous studies have demonstrated the safety of ABO-incompatible pediatric LDLT using preoperative plasmapheresis and rituximab; however, no reports have described the timing and dosage of rituximab administration for pediatric LDLT. This study aimed to describe a safe and effective dosage and timing of rituximab for patients undergoing pediatric ABO-incompatible LDLT based on the experience of our single center. A total of 192 LDLTs in 187 patients were examined. These cases included 29 ABO-incompatible LDLTs in 28 patients. Rituximab was used beginning in January 2004 in recipients older than two yr of age (first period: 375 mg/m(2) in two cases; second period: 50 mg/m(2) in two cases; and 200 mg/m(2) in eight cases). Two patients who received 375 mg/m(2) rituximab died of Pneumocystis carinii pneumonia and hemophagocytic syndrome. One patient who received 50 mg/m(2) rituximab required retransplantation as a consequence of antibody-mediated complications. All eight patients administered 200 mg/m(2) survived, and the mean CD20(+) lymphocyte count was 0.1% at the time of LDLT. In the preoperative management of patients undergoing pediatric ABO-incompatible LDLT, the administration of 200 mg/m(2) rituximab three wk prior to LDLT was safe and effective.

β-D glucan in the portal vein blood is processed by the hepatic reticuloendothelial system, and therefore, it is possible that the β-D glucan kinetics of the peripheral vein blood may be useful as a biological index. In this study, the β-D glucan levels in the peripheral and portal vein blood during liver transplantation were measured in order to study the clinical significance of the molecule.The subjects comprised 20 patients who underwent living donor liver transplantation. In the perioperative period, the β-D glucan levels were measured before liver transplantation, during surgical procedure, then on postoperative days 5, 14 and 21.The portal vein blood showed a significantly higher level of β-D glucan than the peripheral blood (p0.001). A significant difference of β-D glucan levels was observed between the pre-liver transplantation and postoperative days 5 (p=0.048). There was a significant positive correlation between the preoperative β-D glucan level and the period of postoperative hospitalization (p0.001). The patients with fungal infections (35.0%) had a significantly longer period of hospitalization (p=0.019).The β-D glucan kinetics accurately reflects the liver function and fungal infections. The β-D glucan level before liver transplantation can be used to

The use of donors with coagulation FIX deficiency is controversial, and there are no current protocols for peri-transplant management. We herein describe the first reported case of a pediatric LDLT from an asymptomatic donor with mild coagulation FIX deficiency. A 32-yr-old female was evaluated as a donor for her 12-month-old daughter with biliary atresia. The donor's pretransplant coagulation tests revealed asymptomatic mild coagulation FIX deficiency (FIX activity 60.8%). Freeze-dried human blood coagulation FIX concentrate was administered before the dissection of the liver and 12 h afterwards by bolus infusion (40 U/kg) and was continued on POD 1. The bleeding volume at LDLT was 590 mL. On POD 1, 3, 5, and 13, the coagulation FIX activity of the donor was 121.3%, 130.6%, 114.6%, and 50.2%, respectively. The donor's post-transplant course was uneventful, and the recipient is currently doing well at 18 months after LDLT. The FIX activity of the donor and recipient at nine months after LDLT was 39.2% and 58.0%, respectively. LDLT from donors with mild coagulation FIX deficiency could be performed effectively and safely using peri-transplant short-term coagulation FIX replacement and long-term monitoring of the plasma FIX level in the donor.

Although endotoxin (Et) has been used as a biological index of bacterial infections, Et can also be used to evaluate liver functions because Et present in the portal vein blood is processed by the hepatic reticuloendothelial system. In the field of posttransplant management, it is important for liver transplant recipients to monitor the presence of posttransplant bacterial infections and graft liver functions because these results are directly correlated with a graft prognosis. Therefore, the measurement of Et during liver transplantation (LT) may be the detection of posttransplant infections and graft liver functions. This retrospective study investigated whether Et measured by the Et activity assay (EAA) in the peripheral venous blood during living donor LT (LDLT) can predict the incidence of posttransplant bacterial infections and graft liver functions.The study subjects consisted of 21 patients who underwent LDLT between April 2010 and February 2011. Et activity (EA) was measured using the EAA in peripheral venous blood samples collected 1 or 2 days before LDLT, and on postoperative days (PODs) 1, 5, 7, and 14. We included LDLT recipients with intra-abdominal infections, respiratory infections, and bacteremia in the group with posttransplant bacterial infections.The incidence rates of posttransplant bacterial infections or hyperbilirubinemia after LDLT were 57.1%. The LDLT recipients with posttransplant bacterial infections or hyperbilirubinemia had significantly higher levels of EA in comparison with patients without complications before LDLT (0.22 ± 0.10 vs. 0.07 ± 0.05, p0.001), but they had no statistically significant increase of EA between PODs 1 and 14. Based on a receiver operating characteristic curve analysis of pretransplant levels of EA in patients with posttransplant bacterial infections or hyperbilirubinemia, the recommended cutoff value to diagnose posttransplant bacterial infections or hyperbilirubinemia was set at 0.16 (sensitivity 83.3%, specificity 88.9%, and area under the curve 0.940).At a pretransplant level of EA greater than 0.16, patients had an augmented risk for developing posttransplant bacterial infections or hyperbilirubinemia.

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

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