Gold Nanoparticle-Decorated Polymer Particles for High-Optical-Density Immunoassay Probes.

To realize a highly sensitive immunoassay, high-optical-density probes conjugated with antibodies for target antigens are needed to increase the detectability of antigen-antibody complex formation. In this work, gold nanoparticle (NP)-decorated polymer (GNDP) particles were successfully prepared by mixing positively charged polymer particles and negatively charged Au NPs. GNDP particles decorated with NPs of 20 nm in size had higher optical density than the original Au NPs and GNDPs decorated with smaller Au NPs. Using GNDP particles as a probe, a highly sensitive immunoassay for influenza H1N1 hemagglutinin was realized with a minimum detectable concentration of 32.5 pg/mL. These results indicate that GNDP particles have high potential as an immunoassay probe that can be used in practical immunoassay systems for detecting a wide variety of antigens.

The role of liver transplantation in COACH syndrome (Joubert syndrome with congenital hepatic fibrosis): A review of the literature.

BACKGROUND: COACH syndrome is a rare autosomal recessive genetic disease characterized by liver fibrosis, which leads to severe complications related to portal hypertension. However, only a few patients with COACH syndrome undergoing liver transplantation (LT) have been reported. MATERIALS AND METHODS: We herein report the outcomes of four children who underwent LT for COACH syndrome at our institute and review three previously reported cases to elucidate the role of LT in COACH syndrome. RESULTS: All four patients in our institute were female, and three received living donors LT. All patients were diagnosed with COACH syndrome by genetic testing. LT was performed in these patients at 3, 7, 9, and 14 years old. The indication for LT was varices related to portal hypertension in all patients. One showed an intrapulmonary shunt. Blood tests revealed renal impairment due to nephronophthisis in three patients, and one developed renal insufficiency after LT. The liver function was maintained in all patients. A literature review revealed detailed information for three more patients. The indication for LT in these three cases was portal hypertension, such as bleeding from esophageal varices. One patient had chronic renal failure on hemodialysis at LT and underwent combined liver and kidney transplantation. Of these three previous patients, one died from hepatic failure due to de novo HCV infection 3 years after LT. CONCLUSIONS: LT should be considered an effective treatment for COACH syndrome in patients with severe portal hypertension. However, a detailed follow-up of the renal function is necessary.

Living-donor liver transplantation for methylmalonic acidemia patient with hepatocellular carcinoma: A case report and literature review.

BACKGROUND: Methylmalonic acidemia (MMA) is an autosomal recessive disorder caused by defects in propionyl-CoA (P-CoA) catabolism; of note, liver neoplasms rarely occur as a long-term complication of the disorder. Herein, we report the case of a patient with MMA and hepatocellular carcinoma (HCC) who was successfully treated with a living-donor liver transplant (LDLT) following prior kidney transplantation. CASE REPORT: A 25-year-old male patient with MMA underwent LDLT with a left lobe graft because of metabolic instability and liver neoplasms. He had presented with chronic symptoms of MMA, which had been diagnosed by genetic testing. Additionally, he had undergone living-donor kidney transplantation with his father as the donor due to end-stage kidney disease 6 years before the LDLT. He had an episode of metabolic decompensation triggered by coronavirus disease in 2019. Imaging studies revealed an intrahepatic neoplasm in the right hepatic lobe. Due to concerns about metabolic decompensation after hepatectomy, LDLT was performed using a left lobe graft obtained from the patient's mother. Pathological findings were consistent with the characteristics of well-to-moderately differentiated HCC. The postoperative course was uneventful, and the patient was discharged 48 days after the LDLT without any complications. At the 9-month follow-up, the patient's condition was satisfactory, with sufficient liver graft function and without metabolic decompensation. CONCLUSION: This case indicates that although HCC is a rare complication in patients with MMA, clinicians should be aware of hepatic malignancies during long-term follow-up.

Significance of a multidisciplinary approach to congenital extrahepatic portosystemic shunt: A changing paradigm for the treatment.

AIM: To review the current institutional practice to treat patients with congenital extrahepatic portosystemic shunt (CEPS) and to determine the optimal strategy. METHODS: We retrospectively reviewed the records of 55 patients diagnosed with CEPS at our center between December 2008 and March 2022. RESULTS: Among these 55 patients, 44 (80.0%) received treatment for CEPS at a median age of 4.7 years. The most common indication for treatment was cardiopulmonary complications (45.5%). Therapeutic intervention included shunt closure by endovascular techniques (50.0%) or surgery (40.9%), and liver transplantation (9.1%). A total of 11 were classified as short shunt types, and surgical ligation was performed in all to preserve the major vascular system and prevent complications (p < 0.001). Children who received a surgical ligation were more likely to develop complications after shunt closure (p = 0.02). Among seven patients with portopulmonary hypertension (POPH), one patient, who received a shunt ligation at <1 year-of-age, was only able to completely discontinue medication. Most other CEPS-related complications were completely resolved. Post-treatment complications, including thrombosis and symptoms of portal hypertension, were seen in 16 patients. After shunt closure, one patient was scheduled to undergo liver transplantation for progressive POPH and large residual hepatocellular adenoma. During follow-up, one patient without any treatment for CEPS developed POPH 16 years from the diagnosis. CONCLUSION: Earlier therapeutic interventions should be strongly considered for patients with POPH related to CEPS. However, in view of the invasiveness and treatment complications, special attention should be paid to the management of patients with short shunt types.

Successful pediatric liver transplantation case with a positive SARS-CoV-2 test at the time of transplant.

AIM: We report a successful liver transplantation (LT) in a child with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. CASE PRESENTATION: A 3-year-old female patient with decompensated cirrhosis due to Alagille syndrome underwent a split LT with a left lateral segment graft. She had a history of SARS-CoV-2 infection 4 months before LT. She was exposed to SARS-CoV-2 after the decision for organ acceptance. We repeatedly confirmed the negative SARS-CoV-2 test by polymerase chain reaction (PCR) before LT. Liver transplantation was carried out in the negative pressure operational theater with full airborne, droplet, and contact precautions as the patient was considered to be within the incubation period of SARS-CoV-2. The SARS-CoV-2 PCR test became positive in the nasopharyngeal swab specimen at the operation. Remdesivir, the antiviral treatment, was held off due to potential hepatotoxicity and no exacerbation of COVID-19. She received tacrolimus and low-dose steroids per protocol. She remained SARS-CoV-2 positive on postoperative days (PODs) 1, 2, and 5. The presence of antibodies for SARS-CoV-2 at LT was confirmed later. On POD 53, she was discharged without any symptomatic infection. CONCLUSION: This case demonstrated that a positive SARS-CoV-2 result was not an absolute contraindication for a life-saving LT. Liver transplantation could be safely performed in a pediatric patient with asymptomatic COVID-19 and S-immunoglobulin G antibodies for SARS-CoV-2.

Portal vein pressure and flow modulation in pediatric liver transplantation.

Liver transplantation (LT) has been indicated for smaller and more clinically severe patients in recent years. Small biliary atresia (BA) patients often show portal hypoplasia and sclerotic portal vein (PV), which may make PV reconstruction more difficult during the operation. Among PV complications, intraoperative PV thrombosis can be considered a disaster, and it is important to prevent this catastrophic event by the precise assessment of the PV structure and PVF using radiological imaging before and during LT. However, there are no objective parameters to indicate whether sufficient PVF can be obtained. PV pressure (PVP) and PV flow (PVF) have mainly been studied in adult living donor LT, for the purpose of preventing small-for-size syndrome, and PVP has been considered an objective parameter of graft inflow modulation (GIM). In the setting of pediatric LT, GIM is mainly performed to prevent hypoperfusion, and it must be performed before graft implantation. GIM to maximize the PVF of pediatric patients with potentially low PVF in LT consists of the interruption of collateral vessels, the assessment of the usability of the native PV, and technical modifications in PV reconstruction. Reliable objective parameters that represent sufficient PVF before graft implantation are desired. Our recent study proposed that a PVP of ≥25 mmHg before graft implantation can be considered an objective parameter to obtain sufficient PVF (cutoff value: 50 mL/min/100 g of graft weight). Further investigation is needed to determine the best strategy for successful PV reconstruction in pediatric LT.

Optimal liver transplant procedure in progressive familial intrahepatic cholestasis type 1 treated with biliary diversion or intestinal transplantation: Lessons learned from three cases treated with different approaches.

BACKGROUND: Progressive familial intrahepatic cholestasis type 1 (PFIC1) is an autosomal recessive cholestatic liver disorder caused by ATP8B1 gene mutations. Although liver transplantation (LT) is indicated for progressive liver disease, postoperative complications, including severe diarrhea and graft steatohepatitis leading to graft loss, have been reported. CASES: The first patient had jaundice, pruritus, diarrhea, and growth retardation (weight z-score: -2.5; height z-score: -3.7). She underwent LT with total internal biliary diversion (TIBD) to the colon at 2 years of age. Graft biopsy at the 7-year follow-up examination revealed microvesicular steatosis (60%). Her diarrhea improved, and her growth failure was recovering (weight z-score: -1.0; height z-score: -1.7). The second patient underwent sequential intestine-liver transplantation at 8 years of age due to end-stage liver disease (ESLD) and short bowel syndrome caused by massive bowel resection for internal hernia after partial external biliary diversion (PEBD) at 21 months of age. She developed severe pancreatitis induced by steroid-bolus therapy for rejection after transplantation. She died 1.7 years after intestinal transplantation due to an uncontrollable pancreatic abscess and acute respiratory distress syndrome. The third patient underwent PEBD at 15 months of age and received LT with TEBD at 15 years of age due to ESLD with hepatic encephalopathy. Throughout the perioperative period, she showed no abdominal symptoms, including diarrhea and pancreatitis. Graft biopsy at the 2-year follow-up examination revealed macrovesicular steatosis (60%) with inflammation. CONCLUSIONS: The patients showed different outcomes. Effective therapeutic options to mitigate post-LT complications in patients with PFIC1 must be considered individually.

Gallstone ileus at 17 years after living donor liver transplantation: A case report.

BACKGROUND: Gallstone ileus (GI) occurs in <0.1% of all cases of mechanical bowel obstruction. There have been a few reports of GI occurring after Kasai procedures or Roux-en-Y anastomosis for bariatric surgery. We herein report a case of GI that occurred over 17 years after liver transplantation (LT). CASE REPORT: A 33-year-old woman who had undergone living donor LT for biliary atresia at 16 years old and had been regularly followed on an outpatient basis in our hospital presented with the sudden onset of increased abdominal distension, pain, and nausea. Enhanced abdominal computed tomography showed dilatation of the intrahepatic bile duct and the whole intestinal tract of the Roux limb as well as ischemic changes near the jejuno-jejunal anastomosis. On laparotomy, a movable and hard foreign body was palpated in the intestinal tract close to the jejuno-jejunal anastomosis site. Enterotomy was performed, and a 4-cm gallstone was removed. The patient had a good postoperative course and was discharged on postoperative day 12. CONCLUSIONS: Although GI after LT is a rare complication, it may need to be differentiated as a cause of ileus. An accurate differential diagnosis and early reliable intervention for stone removal will help prevent serious bowel complication, which may lead to graft dysfunction.

Adoptive immunotherapy overcomes genetic susceptibility to bloodstream infections due to fc-gamma receptor polymorphisms after liver transplantation.

Single nucleotide polymorphisms (SNPs) in FCGR3A can predict the susceptibility of liver transplant (LT) recipients to bloodstream infections (BSI) and clinical outcomes following living-donor LT (LDLT). Here, we retrospectively analyzed the relationship of adoptive immunotherapy with activated natural killer (NK) cells from perfusate effluents of liver allografts against BSI following LDLT. Higher BSI incidence and lower survival were observed in LT recipients with FcγRIIIa (158F/F or F/V) (n = 81) who did not receive adoptive immunotherapy (n = 55) than in those who did (n = 26) (BSI frequency, 36.4% vs. 11.5%; p = .033; log-rank p = .047). After matching patient background using propensity score, similar results were obtained (BSI ratio, 41.7% vs. 12.5%; p = .049; log-rank p = .039). The predominant BSI pathogens in patients who did and did not receive adoptive immunotherapy were gram-negative rods (n = 3, 100%) and gram-positive cocci (GPC) (n = 15, 65.2%), respectively. The proportion of NK cells administered to patients with BSI was significantly lower than that administered to patients without BSI (Number: 80.3 (29.9-239.2) × 106 cells vs. 37.1 (35.6-50.4) × 106 ; p = .033, percentage; 14.1 (13.3-17.8)% vs. 34.6 (16.5-47)%, p = .0078). Therefore, adoptive immunotherapy with NK cells was associated with the reduced post-transplant BSI related to GPCs due to FcγRIIIa SNP in LT recipients.

Surgical technique and the long-term outcomes of pediatric living donor domino liver transplantation from patients with maple syrup urine disease.

BACKGROUND: The native liver of patients with maple syrup urine disease (MSUD) (1st recipients) can be used as a graft for non-MSUD patients with end-stage liver disease (2nd recipients). This study aimed to demonstrate the optimal operational procedures and the long-term outcomes of 2nd recipients. METHODS: Six 2nd recipients of living donor domino liver transplantation (LD-DLT) (age: 42.5 [22-169] months at DLT) received a native liver as a graft from an MSUD patient at our hospital between June 2014 and April 2020. We reviewed the operational procedures and outcomes of 2nd recipients after LD-DLT. RESULTS: The 2nd recipients' original diseases included biliary atresia, congenital hepatic fibrosis, congenital protein C deficiency, familial hypercholesterolemia, hepatoblastoma, and mitochondrial hepatopathy. Five of the six recipients had a whole liver and one had a right lobe graft. The site at which the vessels of the MSUD liver were dissected prioritized the safety of the 1st recipient. At the end of follow-up, all recipients were doing well without surgical complications. The mean serum amino acid values of the 2nd recipients did not exceed the upper limit of the reference values during the long-term observation period. All patients showed normal growth while maintaining the same z-score of height and weight after LD-DLT as the preoperative level. CONCLUSION: The liver of patients with MSUD can be used safely without concern regarding long-term complications or de novo MSUD development. LD-DLT using the MSUD liver can expand the donor pool as an alternative graft in pediatric LT.

Preemptive liver transplant in two patients with primary hyperoxaluria type 1: Clinical significance of nephrolithiasis and nephrocalcinosis.

BACKGROUND: Although nephrolithiasis (NL) and nephrocalcinosis (NC) are very common features of primary hyperoxaluria type 1 (PH1), the long-term prognosis of NL and NC after preemptive liver transplantation (PLT) has not been elucidated. MATERIAL AND METHODS: We describe the cases of two chronic kidney disease (CKD) stage three patients with different clinical courses after PLT for PH1. RESULTS: The first patient underwent PLT at 7 years of age with an estimated glomerular filtration rate (eGFR) of 47.8 ml/min/1.73 m2 . Two years later, she experienced several episodes of obstructive pyelonephritis due to urolithiasis, and developed septic shock in one of these episodes. At the same time as these episodes, preexisting NL and NC progressively improved, with disappearance on X-ray disappeared at 8 years after transplantation. Her renal function has been maintained with an eGFR of 58.7 ml/min/1.73 m2 . The second patient received PLT at 10 years of age with an eGFR of 58.9 ml/min/1.73 m2 . Her renal function has been maintained with an eGFR of 65.9 ml/min/1.73 m2 . She had repeated urolithiasis which started to appear at 3 years after LT. The radiological findings still show bilateral NL and NC, but the stones in the renal pelvis have shown mild improvement. CONCLUSIONS: Regardless of the regression in NC seen on X-ray, long-term maintenance of the renal function in patients with PH1 with CKD stage 3 can be achieved with PLT. In patients with NL, there is a risk of serious complications due to posttransplant immunosuppressive therapy when obstructive pyelonephritis occurs after LT.

Quantification of Maternal Microchimeric Cells in the Liver of Children With Biliary Atresia.

ABSTRACT: Biliary atresia (BA) is a rare disorder of unknown etiology. There is a debate as to whether maternal microchimerism plays a significant role in the development of BA or in graft tolerance after liver transplantation. Here, we performed quantitative-PCR-based assays for liver tissues of children with BA and other diseases. Maternal cells were detected in 4/13 and 1/3 of the BA and control groups, respectively. The estimated number of maternal cells ranged between 0 and 34.7 per 106 total cells. The frequency and severity of maternal microchimerism were similar between the BA and control groups, and between patients with and without acute rejection of maternal grafts. These results highlight the high frequency of maternal microchimerism in the liver. This study provides no evidence for roles of microchimerism in the etiology of BA or in graft tolerance. Thus, the biological consequences of maternal microchimerism need to be clarified in future studies.

Impact of sarcopenia in infants with liver transplantation for biliary atresia.

While sarcopenia is an important predictor of LT outcomes in adults, few studies have examined the association of sarcopenia with LT outcomes in pediatric patients. We investigated the clinical influence of sarcopenia on the post-transplant outcomes in infants with BA. To define sarcopenia in infants, the cross-sectional area of the tPMA in 93 healthy control infants was measured by computed tomography. Sarcopenia was defined as a tPMA lower than two standard deviations below the mean of healthy control infants. Eighty-nine infants with BA with a median age at LT of 7.6 months old were enrolled. The clinical characteristics and outcomes of LT were verified in the sarcopenia group (n = 21) and non-sarcopenia group (n = 68). The sarcopenia group had a significantly longer operation time and greater blood loss during LT than the non-sarcopenia group (P = .03 and 0.02). The incidence of portal vein stenosis and post-operative bloodstream infection was also significantly higher in the sarcopenia group than in the non-sarcopenia group (23.8% vs 4.4%, P = .02 and 28.6% vs 10.3%, P = .04, respectively). The total length of hospital stay did not differ significantly. The 1-year patient and graft survival rates tended to be lower in the sarcopenia group than in the non-sarcopenia group (90.5% vs 98.5%, P = .07 and 85.7% vs 97.1%, P = .05, respectively). Sarcopenia in infants with BA may be associated with the patient survival and serve as an effective marker for post-operative outcomes of LT.

Efficacy of intraoperative cine-portogram for complicated portal vein reconstruction in pediatric living donor liver transplantation.

Sufficient PV flow is necessary to achieve successful PV reconstruction in pediatric LDLT. IOCP can be used to assess the severity of PV stenosis and to identify potential portosystemic collateral pathways. The present study reviewed the utility of IOCP and the outcomes of patients who underwent assessment with an IOCP. Consecutive primary LDLTs were performed in 488 pediatric recipients between November 2005 and October 2019. IOCP was used in patients who were unable to achieve sufficient PV flow after the ligation of collaterals. In total, 11 patients underwent IOCP to assess potential portosystemic collateral pathways. The median age and body weight was 8 months (IQR, 6-11 months) and 6.6 kg (IQR, 5.7-8.9 kg), respectively. The reasons for using the IOCP were recurrent PV thrombus in seven patients and insufficient PV flow in four patients. IOCP revealed remaining collaterals in six patients and residual hypoplastic PV in eight patients. Two patients required additional interruption of the potential collaterals under IOCP, which were unable to be recognized as a dominant portosystemic collateral pathway on preoperative imaging. All eight patients with residual hypoplastic PV required vein graft interposition for the complete removal of the hypoplastic PV. All the patients are currently doing well with a median follow-up period of 4.9 years (IQR, 2.2-5.6 years). IOCP can be an effective tool for precisely detecting occult portosystemic collateral pathways and for assessing the patency of the PV anastomosis in pediatric LDLT.

Outcomes of liver transplantation for mitochondrial respiratory chain disorder in children.

AIM: Mitochondrial respiratory chain disorder (MRCD) can cause acute liver failure (ALF), which may necessitate liver transplantation (LT). However, MRCD is often difficult to diagnose before LT and the indications of LT are controversial due to the likelihood of progressive neurological disease. The present study further characterized the patient population and described the outcomes. METHODS: Thirteen patients who underwent LT for MRCD from November 2005 to May 2020 were enrolled in this study. RESULTS: Six of 13 MRCD patients were diagnosed with a mitochondrial inner membrane protein 17-related mitochondrial DNA depletion syndrome (MTDPS). Overall, nine survived with a median follow-up of 1.8 years (IQR, 1.3-5.1 years); four died within 2 years. In the long-term, seven survivors showed no progression of hypotonia after LT and attended a normal kindergarten or primary school. Neurological abnormalities were observed in two survivors, including vison loss related to Leber's hereditary optic neuropathy in one patient and psychomotor retardation related to Leigh syndrome in the other. Three non-survivors after LT were diagnosed with MTDPS and died of severe pulmonary hypertension, which had developed at 8, 9, and 18 months after LT (n=1 each). The remaining patient died of postoperative respiratory infection with respiratory syncytial virus. CONCLUSION: The long-term results support the performance of LT in patients with MRCD, although a genetic diagnosis is preferable for determining the accurate indications for LT in these patients. Furthermore, care should be taken to avoid complications due to mitochondrial dysfunction during the long-term follow-up.

The extracorporeal circulation with transdiaphragmatic approach in living-donor liver transplantation for HB with atrial extension of tumor thrombus: A case report.

Surgical intervention for HB with tumor thrombi extending into the IVC and the RA might requires careful planning of the surgical procedures, including vascular reconstruction and extracorporeal circulation. We herein report a successful case of LDLT for HB with atrial extension of a tumor thrombus by extracorporeal circulation with a transdiaphragmatic approach. The patient was a 5-year-old boy with PRETEXT IV HB with a tumor thrombus that extended into the IVC and the RA. After 4 cycles of chemotherapy and resection of bilateral lung metastases, the size of the primary HB tumor decreased. As the tumor extension from the LHV to the RA had decreased but was still present, we performed LDLT with tumor thrombectomy. The central part of the diaphragm was sagittally incised to expose the suprahepatic IVC and the RA. Venovenous bypass was achieved from the right femoral vein and IMV to the RA En bloc resection of the native liver with the tumor thrombus was then performed. HV anastomosis was made between the newly created orifice on the IVC and the graft LHV. The duration of LDLT was 10 hours and 44 minutes (extracorporeal circulation time: 78 minutes). Pediatric LT for HB with the extension of tumor thrombi into the RA under extracorporeal circulation is a feasible option and allows for the expansion of the indications for transplantation for children with unresectable liver tumors.

Fatal Epstein-Barr virus-associated hemophagocytic lymphohistiocytosis with virus-infected T cells after pediatric multivisceral transplantation: A proof-of-concept case report.

BACKGROUND: EBV-associated HLH driven by EBV-infected CD8+ T cells is a rare complication after pediatric solid organ transplantation. The etiology and disease spectrum of post-transplant EBV-HLH are poorly understood, and making a precise diagnosis and providing optimal treatment remain a challenge. METHODS/CASE DESCRIPTION/RESULTS: We report a 2-year-old multivisceral transplant recipient who developed fever and cytopenia with a persistent high EBV-load state. Repeated tissue examinations and CT scans could not identify a localized mass, which is the key to the diagnosis of PTLD as per the WHO classification. Hence, EBV-HLH was diagnosed by clinical manifestations as well as characterization of EBV-infected cells, pathological examination on cell block of pleural effusion and clonality analysis. This EBV-HLH did not respond to intensive chemotherapy, resulted in the recipient's death, acting similarly to hematological malignancy. CONCLUSIONS: Characterization of EBV-infected cells in peripheral blood should be considered when persistent high EBV loads develop with symptoms consistent with PTLD, but no evidence of localized mass, and the tissue diagnosis is unavailable after pediatric solid organ transplantation.

Immunological features and complications in patients with glycogen storage disease 1b after living donor liver transplantation.

BACKGROUND: LT is an elective treatment choice for children diagnosed with GSD1b that can improve their quality of life and stabilize their glucose intolerance. However, careful attention should be paid to immunosuppression after LT due to the susceptibility to infection because of neutropenia and neutrophil dysfunction in GSD1b patients. This study revealed the immunological features and complications in the early post-LT period. METHODS: We compared findings between 11 (1.9%) children with GSD1b and 273 children with BA. Analyses using the PSM were performed to overcome selection bias. RESULTS: Despite persistent low tacrolimus trough levels in GSD1b patients, none of these children developed TCMR within 1 month after LDLT (GSD1b: 0/11 [0%] vs. BA: 86/273 [31.5%], p = .038). This result was also confirmed in PSM. The incidence of bloodstream infections was higher in GSD1b patients than in BA patients in the early phase of the post-transplant period (GSD1b: 4/11 [36.4%] vs. BA: 33/273 [12.1%], p = .041), but not reach statistical significance in PSM. In a phenotypic analysis, the ratio of CD8+ T cells in GSD1b recipients' peripheral blood mononuclear cell samples was lower than in recipients with BA through the first month after LDLT. CONCLUSIONS: We found that GSD1b recipients were more likely to develop postoperative bloodstream infection than recipients with BA but did not experience TCMR despite low tacrolimus levels in the early post-LDLT period. A tailored immunosuppression protocol should be prepared for GSD1b recipients after LDLT.

Impact of prolonged clamping of the portal vein during liver transplantation in infants with biliary atresia: renewed interest in a long-standing issue.

PURPOSE: Various approaches to portal vein (PV) reconstruction have been described; however, there is still scope to improve the safety and efficiency of how PV anastomosis is performed in infants. METHODS: We analyzed, retrospectively, the predictive factors for PV reanastomosis during living donor liver transplantation (LDLT) in 117 infants (< 1 year old) with biliary atresia (BA). RESULTS: Twenty-six infants required PV reanastomosis because of intraoperative PV thrombosis in 21 and insufficient PV flow in 5. Univariate analysis identified multiple previous laparotomies and a prolonged anhepatic phase (AHP) as significant risk factors for repeated PV anastomosis. The AHP cutoff value for identifying patients requiring PV reanastomosis was 134 min. Multivariate analysis revealed prolonged AHP > 134 min (odds ratio, 15.98; 95% confidence interval, 5.05-50.6; P < 0.001) as an independent risk factor for repeated PV anastomosis. The plasma D-dimer and fibrinogen degradation product concentration just after reperfusion were significantly higher in patients requiring PV reanastomosis (P < 0.001). Patients requiring reanastomosis of the PV had a higher incidence of PV complications after LDLT than those who did not need PV reanastomosis (P = 0.01). CONCLUSION: Attempting to minimize the AHP is indispensable for successful LDLT in infants with BA.

The morphological and histopathological assessment of Alagille syndrome with extrahepatic bile duct obstruction: the importance of the differential diagnosis with subgroup "o" biliary atresia.

PURPOSE: The differential diagnosis between Alagille syndrome (AGS) with extrahepatic bile duct obstruction (EHBDO) and biliary atresia (BA) is difficult. We report a case series of AGS with EHBDO with detailed validation of the morphological and histopathological features for the differential diagnosis of BA. METHODS: Six liver transplantations (LTs) were performed for AGS with EHBDO. All patients were diagnosed with BA at the referring institution and the diagnosis of AGS was then confirmed based on a genetic analysis before LT. We verified the morphological and histopathological findings of the porta hepatis and liver at the diagnosis of BA and at LT. RESULTS: All patients had acholic stool in the neonatal period and were diagnosed with BA by cholangiography. The gross liver findings included a smooth and soft surface, without any cirrhosis. The gross findings of the porta hepatis included aplasia of the proximal hepatic duct, or subgroup "o", in five patients. The histopathological examination of the EHBD also revealed obstruction/absence of the hepatic duct. There were no patients with aplasia of the common bile duct. CONCLUSIONS: Aplasia of the hepatic duct and the macroscopic liver findings may help in to differentiate between AGS with EHBDO and BA.