Successful living donor liver transplantation for liver failure due to maternal T cell engraftment following cord blood transplantation in X-linked severe combined immunodeficiency disease: Case report.

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.

Ultrasonographically guided percutaneous transhepatic liver biopsy after pediatric liver transplantation.

BACKGROUND: Complications associated with ultrasonographically guided percutaneous transhepatic liver biopsy (PTLB) after liver transplantation (LT) have been rarely reported, and there is no consensus about its safety. We retrospectively reviewed the safety and outcomes of PTLB after pediatric LT. METHODS: Between January 2008 and December 2019, 8/1122 (0.71%) pediatric patients who underwent ultrasonographically guided PTLB after LT developed complications. The median age at PTLB was 7.8 years (range 0.1-17.9). Grafts included left lobe/left lateral segment in 1050 patients and others in 72. PTLB was performed using local anesthesia±sedation in 1028 patients and general anesthesia in 94. RESULTS: Complications after PTLB included acute cholangitis in 3 patients, sepsis in 2, respiratory failure due to over-sedation in 1, subcapsular hematoma in 1, and intrahepatic arterioportal fistula in 1. The incidence of complications of PTLB in patients with biopsy alone and those with simultaneous interventions was 0.49% and 3.19%, respectively (p = .023). Patients who developed acute cholangitis, respiratory failure, subcapsular hematoma, and arterioportal fistula improved with non-operative management. Of two patients with sepsis, one underwent PTLB and percutaneous transhepatic portal vein balloon dilatation and developed fever and seizures the following day. Sepsis was treated with antibiotic therapy. Another patient who underwent PTLB and exchange of percutaneous transhepatic biliary drainage catheter developed fever and impaired consciousness immediately. Sepsis was treated with antibiotic therapy, mechanical ventilation, and continuous hemofiltration. CONCLUSIONS: Percutaneous transhepatic liver biopsy after pediatric LT is safe. However, combining liver biopsy with simultaneous procedures for vascular and biliary complications is associated with an increased risk of complications.

The Causes and Outcomes of Early Relaparotomy Following Pediatric Living Donor Liver Transplantation.

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.

Increased tacrolimus blood concentration by Beni-Madonna - a new hybrid citrus cultivar categorized as 'Tangor', in a liver transplant patient: likely furanocoumarin-mediated inhibition of CYP3A4 or P-glycoprotein.

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.

Interventional radiology treatment for vascular and biliary complications following pediatric living donor liver transplantation - a retrospective study.

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.

Rescue case of low birth weight infant with acute hepatic failure.

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.

Improvement of Predictivity of Teicoplanin Serum Trough Concentrations at Steady State Calculated by Vancomycin Pharmacokinetic Parameter.

According to a recent study and meta-analysis, trough levels of >10 µg/mL teicoplanin (TEIC) may be acceptable for the treatment of uncomplicated infection, but no method of TEIC personalized medicine has been established. Vancomycin (VCM) and TEIC are glycopeptide antibiotic agents effective against methicillin-resistance Staphyloccocus aureus. This study aimed to establish TEIC personalized medicine at a steady state calculated by VCM pharmacokinetic parameters. Bayesian forecasting and population mean methods were employed to estimate individual total VCM clearance (CL) using existing population pharmacokinetics (PPK) parameter, and the differences between the CL calculated by these two methods were defined as ΔCL. Serum drug concentration data for patients treated with TEIC were collected at a steady state concentration (>96 h post infusion). There was a significant relationship between the prediction error of TEIC trough level and ΔCL. The relation between ΔCL and TEIC trough concentration at steady state was used to develop the following equation to determine the maintenance dose: TEIC (µg/mL)=1.1119X-6.124ΔCL+3.9164 (X is defined as TEIC trough concentration calculated from the PPK parameter). The results of this study indicated that it is possible to improve the prediction error of TEIC trough concentration at a steady state for patients who have received VCM therapy.

Antenatal immunoglobulin for prevention of neonatal hemochromatosis.

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.

Imaging of built-in electric field at a p-n junction by scanning transmission electron microscopy.

Precise measurement and characterization of electrostatic potential structures and the concomitant electric fields at nanodimensions are essential to understand and control the properties of modern materials and devices. However, directly observing and measuring such local electric field information is still a major challenge in microscopy. Here, differential phase contrast imaging in scanning transmission electron microscopy with segmented type detector is used to image a p-n junction in a GaAs compound semiconductor. Differential phase contrast imaging is able to both clearly visualize and quantify the projected, built-in electric field in the p-n junction. The technique is further shown capable of sensitively detecting the electric field variations due to dopant concentration steps within both p-type and n-type regions. Through live differential phase contrast imaging, this technique can potentially be used to image the electromagnetic field structure of new materials and devices even under working conditions.

Direct observation of dopant distribution in GaAs compound semiconductors using phase-shifting electron holography and Lorentz microscopy.

Phase-shifting electron holography and Lorentz microscopy were used to map dopant distributions in GaAs compound semiconductors with step-like dopant concentration. Transmission electron microscope specimens were prepared using a triple beam focused ion beam (FIB) system, which combines a Ga ion beam, a scanning electron microscope, and an Ar ion beam to remove the FIB damaged layers. The p-n junctions were clearly observed in both under-focused and over-focused Lorentz microscopy images. A phase image was obtained by using a phase-shifting reconstruction method to simultaneously achieve high sensitivity and high spatial resolution. Differences in dopant concentrations between 1 × 10(19) cm(-3) and 1 × 10(18) cm(-3) regions were clearly observed by using phase-shifting electron holography. We also interpreted phase profiles quantitatively by considering inactive layers induced by ion implantation during the FIB process. The thickness of an inactive layer at different dopant concentration area can be measured from the phase image.

Impact of endotoxin measured by an endotoxin activity assay during liver transplantation.

BACKGROUND: Endotoxin (Et) in the portal vein blood is processed by the hepatic reticuloendothelial system. Thus, it is possible that the Et kinetics of the peripheral venous blood may be useful as a biological index that can be used to evaluate liver function. In this study, we measured Et using the endotoxin activity assay in peripheral venous blood during living donor liver transplantation (LDLT), to study its clinical significance. METHODS: Subjects were 17 patients who underwent LDLT. In the perioperative peripheral venous blood, was measured Et activity (EA) using the endotoxin activity assay at 1 or 2 d before LT, and then on 1, 5, 7, 14, and 21 postoperative days. RESULTS: Patients with infections had significantly higher EA levels compared with those without complications before LDLT and 14 postoperative days (P = 0.038 and 0.027, respectively). The average EA level of patients with infections and without complications before LT was 0.22 and 0.08, respectively (P = 0.038). Patients with an EA level higher than 0.20 before LDLT had a significantly longer period of hospitalization compared with those without complications (P = 0.038). CONCLUSIONS: A preoperative EA level more than 0.20 is a high risk factor for post-transplant infection and a prolonged period of hospitalization.

Impact of enzyme activity assay on indication in liver transplantation for ornithine transcarbamylase deficiency.

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

The role of operative intervention in management of congenital extrahepatic portosystemic shunt.

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

Impact of hepatic clearance of endotoxin using endotoxin activity assay.

BACKGROUND: Endotoxin (Et) in the portal vein blood is processed by the hepatic reticuloendothelial system, and therefore, it is possible that the hepatic clearance of Et may become a biological index for liver function. In this study, Et levels of preoperative peripheral and portal vein blood at the time of liver transplantation (LT) were measured in order to study the meaning. METHODS: The study population comprised 19 patients in whom pediatric living donor LT was performed. In the preoperative peripheral and the portal vein blood at the time of LT, we measured Et activity (EA) by the Et activity assay (EAA) and the Limulus amebocyte lysate (LAL) method. RESULTS: The preoperative peripheral vein blood showed a low EA in all cases. In the EA of the peripheral and the portal vein blood, the latter showed a significantly high level (p = 0.049). With the LAL method, 5.3% (2/38) of patients were positive for Et. CONCLUSIONS: The EAA is considered to be superior to the LAL method for the detection of Et, even in low endotoxinemia, and is also capable of elucidating the Et kinetics by accurately reflecting hepatic clearance.

Indication of liver transplantation for jaundice-free biliary atresia with portal hypertension.

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