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Extracorporeal membrane oxygenation (ECMO) is used for cardiopulmonary dysfunction. Hepatopulmonary syndrome (HPS) occurs in the setting of liver failure and may cause hypoxemia. Previous reports have described the use of ECMO for HPS after liver transplant. Our patient is a 19-month-old female with biliary atresia, an interrupted inferior vena cava, and HPS on 8 liters per minute of high-flow oxygen. Following liver transplantation, her postoperative course was complicated by severe hypoxemia requiring ECMO. Due to her interrupted inferior vena cava, our standard bi-caval cannula could not be used. Hence, a 16-French double lumen venovenous right internal jugular to right atrial cannula was used to provide extracorporeal life support. She was decannulated after 17 days, remained intubated for 2 days, and weaned to room air over the next 3 weeks. This is the third pediatric liver transplant patient supported with ECMO identified in the literature, and the youngest and smallest of those reported. This approach to cannulation is unique because of the use of a double lumen venovenous cannula for HPS in a child, selected due to complex anatomy. Posttransplant ECMO may provide pediatric patients with HPS and posttransplant hypoxemia a period of support for their pulmonary remodeling and recovery from HPS.

Unlabelled: Posttransplant lymphoproliferative disorder (PTLD) causes significant morbidity and mortality in pediatric recipients of liver transplantation (LT)., Objective: Describe the incidence of PTLD and symptomatic Epstein-Barr virus (SEBV) disease in a large multicenter cohort of children who underwent LT with a focus on the risk factors and changes in incidence over time. SEBV and PTLD were prospectively determined in 2283 subjects who had undergone LT for the first time with at least 1 year of follow-up in the Studies of Pediatric Liver Transplantation database. SEBV was defined with specific criteria, and PTLD required tissue confirmation. The incidence of SEBV and PTLD was determined with a Kaplan-Meier analysis. Univariate and multivariate modeling of risk factors was performed with standard methods. SEBV occurred in 199 patients; 174 (87.4%) were EBV-negative at LT. Seventy-five patients developed PTLD, and 64 (85.3%) of these patients were EBV-negative at LT. Among the 2048 patients with at least 2 years of follow-up, 8.3% developed SEBV by the second year after LT, and 2.8% developed PTLD. There were lower rates of SEBV (5.9% versus 11.3%, P < 0.001) and PTLD (1.7% versus 4.2%, P = 0.001) in 2002-2007 versus 1995-2001. In 2002-2007, tacrolimus and cyclosporine trough blood levels in the first year after LT were significantly lower, and fewer children were receiving steroids. Biliary atresia, and recipient EBV status were correlated. In a multivariate analysis, era of LT, recipient EBV status, and frequent rejection episodes were associated with SEBV and PTLD. The incidence of SEBV and PTLD is decreasing in pediatric LT recipients concomitantly with a reduction in immunosuppression. Younger recipients and those with multiple rejections remain at higher risk for SEBV and PTLD., (© 2013 American Association for the Study of Liver Diseases.)

A 6-week-old boy presented with fever, pallor, and hepatomegaly. Ultrasound showed a huge midline abdominal mass. β-human chorionic gonadotropin was markedly elevated, suggesting a diagnosis of infantile choriocarcinoma of the liver. A biopsy confirmed the diagnosis. The patient received 6 cycles of bleomycin, cisplatin, and etoposide with significant decrease in tumor size. However, the tumor remained unresectable. A donor liver became available, and the infant underwent successful liver transplantation. He received 2 posttransplant cycles of moderate dose of methotrexate. This case shows the use of liver transplantation in cases of infantile choriocarcinoma of the liver where the tumor remains unresectable despite chemotherapy.

Telemedicine provides the opportunity to bring medical expertise to the bedside, even if the medical expert is not physically near the patient. Internet technology has facilitated telemedicine allowing for voice, video and other data to be exchanged between remote locations. To date, applications of telemedicine to anesthesia (Teleanesthesia) have been limited. Previous work by Cone et al., (Anesth Analg 2006;1463-7) demonstrated the ability to direct an anesthetic in a remote location using satellite communication. In this report, we describe the use of telemedicine to support two cases of elective living related pediatric liver transplants performed at the Narayana Hrudayalaya Institute of Medical Sciences in Bangalore, India with preoperative and intraoperative consultation provided by physicians at the Children's Hospital of Philadelphia.

AV fistula is a rare but serious complication following pediatric liver transplant and may lead to graft loss. Our aim was to describe two pediatric centers' experience with the diagnosis, treatment and outcomes of children who presented with AV fistulas post-liver transplantation We report five cases of late arterio-portal fistula following liver transplantation. Four children were successfully treated with coil embolization. All of the children in this series had liver biopsies within 2-6 months of their AV fistula diagnosis. All biopsies were performed using a Bard Monopty 18 gauge needle with no ultrasound guidance and only one pass per biopsy. Two children also had PTC 4-8 months prior to their diagnosis of AV fistula. Three of the five children in this series had GI bleeds requiring banding or sclerotherapy. The other two had varices found on CT scan. All five cases in this series had ascites on their initial presentation. Four out of the five children had a history of non-compliance and the other child had a history of malabsorption and chronic diarrhea.

Although non-compliance in pediatric liver transplants is known to be a major cause of late graft loss and patient mortality, follow-up seems inconsistent. As liver transplant becomes a luxury because of the shortage of organs, the need to maximize graft and patient survival by intense monitoring becomes a necessity. When evaluating children with elevated liver enzymes post-transplant, early or late non-compliance should always be suspected. The risk of non-compliance in children with chronic illness varies from 10 to 89%. In a study by Sudan et al. non-compliance was one of the leading causes of late mortality in children age 10-17 yr. Although it is well documented that teenagers have a high rate of non-compliance, the rate in the younger children has not been documented. In our series, we found that parental non-compliance comprises the majority of our problems with liver dysfunction, hospitalization, and graft loss. The purpose of this study was to evaluate the incidence of non-compliance in children post-liver transplant. A retrospective chart review of patient records from admissions and outpatient records was performed for documentation of elevated enzymes and low immunosuppressive levels. From July 1987 to December 2002, our program performed 266 liver transplants in 234 children, with 1-yr graft survival of 84% and 1-yr patient survival of 90%. Our overall patient survival was 85% with 77% graft survival. There were 40 children with documented non-compliance with mild to severe liver dysfunction in this study. Twenty-eight of these children were younger than 10 yr [28 of 40 (46%) <5 yr], and 12 (30%) were older than 10 yr at the time of rejection. In 10 of 40 children, there was one documented incident of non-compliance, while 26 of 40 had two to four incidents, and four had five or more documented events. Our children (50%) came from two-parent households. The remaining 50% were from single households. In 27 of 40 (68%) children, rejection was confirmed by liver biopsy. In children on cyclosporine (Neoral; Novartis, East Hanover, NJ, USA) with a known history of non-compliance and low immunosuppressive levels, C2 monitoring was performed to verify absorption. Admission for drug monitoring and verification of non-compliance was accomplished in 32 of 40 (80%). Four of the 40 children (10%) were retransplanted, and one child had died. In conclusion, non-adherence to medications remains a major source of graft loss and morbidity post-transplant. We found that non-compliance crosses all socio-economic and cultural groups and that flexibility of clinic hours, shortened time between visits, and decreased numbers and times of medication will increase adherence.

We report the management of a patient with the late onset of chronic graft-versus-host disease (GVHD) after orthotopic liver transplantation. GVHD is a rare complication of solid organ transplants that usually presents early after transplantation and is fatal in the majority of cases. Our patient differs from the typical patient with GVHD in that the onset of her disease was very late. Although most treatment to date consisted of an increase in immunosuppressive therapy, our patient showed an excellent response to a reduction. This resulted in the abatement of the symptoms of GVHD and the preservation of her allograft function.

The optimisation of cyclosporin therapy remains a challenge because of the very narrow therapeutic window and the highly variable pharmacokinetics of the drug. Therefore, there has been a concerted effort in the clinical transplant community to explore and test cyclosporin monitoring tools and techniques that will allow blood concentrations of cyclosporin to be maintained within the narrow therapeutic window in order to maximise efficacy and minimise toxicity. Absorption profiling is a simple and accurate technique for adjusting dosages of cyclosporin microemulsion that utilises an estimation of the rate and extent of cyclosporin absorption in order to optimise immunosuppression in the individual patient. Two estimation tools in particular are an abbreviated area under the concentration-time curve (AUC) for the first 4 hours postdose and a single sampling point at 2 hours postdose. These 2 monitoring strategies have not only been validated as an accurate estimation of cyclosporin bioavailability but have been demonstrated to significantly improve clinical outcomes in patients compared with traditional trough concentration monitoring. The evidence presented in this review demonstrates that absorption profiling results in the following clinical benefits compared with trough concentration monitoring: (i) reduced incidence of acute rejection; (ii) reduced severity of rejection episodes; (iii) reduced nephrotoxicity; and (iv) a rational basis for dosage adjustments. The optimisation of immunosuppressive therapy continues to be a major priority in the management of the organ transplant recipient. Absorption profiling is a sensitive and practical approach for optimising the dosage of cyclosporin microemulsion, and can further extend the benefits of cyclosporin immunosuppression in the individual patient.

Background/purpose: Biliary anastomotic strictures (BAS) after left lateral segment liver transplantation (LLST) may cause graft dysfunction, sepsis, and patient mortality. A review of the authors' experience was performed to better characterize the risk factors and corrective management., Methods: The medical records of 9 children who underwent a LLST in whom a BAS developed from 1989 to the present were reviewed retrospectively., Results: Seventy-five of 199 liver transplants (38%) at the authors' institution since 1989 have been LLST. BAS developed in 12% of these cases. BAS were diagnosed less than 12 months after transplantation in 4 children (mean, 7.5 months; range, 5 to 11 months) and greater than 12 months in 5 children (mean, 37 months; range, 14 to 72 months). Early strictures (<12 months) were associated with hepatic artery thrombosis (n = 1), and posttransplant bile leak (n = 1) and ducts from segment II and III exiting separately from the left lateral segment (n = 2). The diagnosis of BAS was heralded by episodes of liver biopsy-proven cholangitis in all patients and confirmed radiographically. Seven children underwent successful biliary exploration and revision of the hepaticojejunostomy. Two of these children ultimately required retransplantation secondary to chronic graft rejection., Conclusions: BAS in LLST are a source of significant morbidity and should be considered in children after LLST who present with cholangitis. Surgical correction is possible in most cases.

Background/purpose: Children who require a liver transplant at an early age risk chronic allograft rejection (CAR) and other causes of allograft loss. Multiple retransplants may be required for long-term patient survival. The authors evaluate this approach based on our results and technical difficulties., Methods: Charts of 7 children who received 3 or more liver transplants from 1989 to the present were reviewed retrospectively., Results: A total of 151 children required liver transplantation at our institution since 1989. Of these, 4 boys and 3 girls (mean age, 6.2 years; range, 3 to 14 years) have received 3 or more allografts. The etiology of liver failure for the penultimate allograft was CAR (n = 6) and hepatic artery thrombosis (HAT; n = 1). Five cases required modification of portal vein or hepatic artery anastomoses. Two patients with vena caval strictures required supradiaphragmatic vena caval reconstruction. The original Roux-en-Y limb was adequate for biliary reconstruction in all cases. Five children currently are alive (survival rate, 71%) with good graft function having had a mean follow-up of 23 months (range, 2 to 48 mos.)., Conclusions: The operative procedure for the multiple hepatic transplant child is challenging. The transplant team must be prepared for intraoperative issues such as extended organ ischemia time during hepatectomy, extensive blood loss, and potential need for creative organ revascularization techniques. Overall, multiple retransplant results are good and justify the use of multiple allografts.

From December 1993, St Christopher's Hospital for Children, Philadelphia, PA, USA has provided living donors the opportunity to donate a portion of their liver to children who are critically ill. This report evaluates the results of living donor liver transplants (LDLT) in critically ill children. We retrospectively reviewed the first 22 LDLT at our institution and compared the patient and graft survival of the nine critically ill children with the 13 stable children. Twenty-two LDLT have been performed at our institution between December 1993 and October 1997. Nine of 22 transplants [United Network for Organ Sharing (UNOS) Status I] were performed in children who were critically ill. Thirteen of the LDLT (UNOS Status II and III) were performed on stable children either in the hospital or admitted electively from home. The median weight and age at the time of transplant were 7 kg (range 4.6-54.5 kg) and 16 months (range 3 months-12 yr), respectively, and there was no statistical difference between the two groups. In critically ill children the 1-yr allograft and patient survival was 66% and 89%, respectively, exceeding the published results from UNOS for patients on life support (59.5% graft and 69.7% patient survival at 1 yr). One-yr allograft and patient survival in the stable children was 92.3% and 100%, respectively. All living donors are alive and well with normal liver function. In conclusion, our results show that LDLT is a viable approach for transplantation in critically ill children with liver failure and should be offered to potential donors.

Black transplant recipients are associated with low cyclosporine bioavailability, which may contribute to the poorer clinical outcomes observed with these patients. In this analysis, we compared cyclosporine exposure in black (n = 9) and nonblack (n = 18) pediatric maintenance liver transplant recipients by using steady-state pharmacokinetic profiles obtained after administration of the original and microemulsion formulations of cyclosporine. Treatment with the original cyclosporine formulation resulted in lower mean dose-normalized, area under the concentration-versus-time curve values for black compared with nonblack pediatric liver transplant recipients. On conversion to the microemulsion formulation of cyclosporine, black and nonblack patients experienced increases in cyclosporine bioavailability of 102% and 39%, respectively (P =.009 and P =.001). Because the increase in mean bioavailability was substantially greater for blacks, area under the concentration-versus-time curve values for this pediatric subpopulation became similar to those levels obtained for nonblacks receiving the microemulsion formulation for cyclosporine. When patients were further stratified by age, ethnic differences in bioavailability with the original formulation of cyclosporine were most apparent in the 1- to 5-year age group. Conversion to the microemulsion formulation resulted in a 164% increase (P =.05) in bioavailability for black patients within this age group such that, again, these levels became similar to area under the concentration-versus-time curve values obtained for young nonblacks receiving cyclosporine for microemulsion. Improvements in cyclosporine bioavailability after administration of the microemulsion formulation of cyclosporine may translate to improved long-term graft and patient outcomes for black pediatric liver transplant recipients.

Background/purpose: Acute liver failure in the pediatric population is a rare but highly lethal health problem. Sometimes it is difficult to predict who will benefit from liver transplantation. The authors report on their experience in the past 8 years at a pediatric transplant center., Methods: A retrospective chart review was performed on all children referred to the liver transplant (TX) service with the diagnosis of acute hepatocellular dysfunction (AHD) from 1988 to 1996. Presentation, chemistries, and clinical course were evaluated. Statistical analysis was performed using analysis of variance., Results: Twenty-six children underwent evaluation. Seventeen patients fulfilled the criteria for fulminant hepatic failure (FHF). Eleven patients recovered without TX, 14 received a TX, and one died awaiting TX. Of those that received a TX, four died in the early postoperative period and 10 survived (mean follow-up of 4.2 years). There was a wide range in most laboratory values. Serum bilirubin levels, ammonia levels, and coagulation parameters, however, reached statistical significance in patients requiring transplant. The most consistent discriminators of need for transplantation and outcome were neurological findings and multisystem organ failure. Children who recovered without TX had no seizures and minimal encephalopathy. Of the 15 children who were recommended for TX, six had seizures and all had encephalopathy, 12 having grade III or IV. All five nonsurvivors had respiratory failure early in their clinical course, and four of five nonsurvivors also had renal failure., Conclusions: There is significant overlap in the presentation and laboratory findings of children who present with AHD or FHF. Neurological status was an important discriminator of need for transplantation. Patients who presented with multisystem organ failure, including renal failure and respiratory failure, had 100% mortality rate despite liver transplantation.

Background/purpose: Transplantation for rejection is a requirement in liver transplant recipients when allograft failure is imminent. The authors evaluated the outcome of these children and their allografts., Methods: The medical records of 129 children who received a liver transplant were reviewed retrospectively. Twelve children required transplantation for biopsy-proven rejection--10 chronic and two acute. Overall patient and graft survival were compared with children receiving primary liver transplants. The current allograft function of the patients undergoing transplants was also reviewed. Statistical significance was determined by Fisher's Exact test., Results: Twelve children received at least one retransplant for biopsy-proven rejection. Graft survival at 1 year was 58% (v 79% for primary transplants) and patient survival was 83% (vs 89%). Two allografts were lost because of primary allograft nonfunction. Three additional allografts were lost-two to recurrent rejection and one to hepatic artery thrombosis. Two patients who lost a second transplant to rejection required a total of seven transplants to treat rejection. Two children died, one of primary nonfunction and one of adenovirus pneumonia. The 10 surviving patients all have excellent graft function (total bilirubin, 0.74 +/- 0.38, aspartate aminotransferase, 40 +/- 22)., Conclusion: These data suggest that transplantation for rejection can be accomplished safely with a patient survival rate comparable to primary liver transplantation; however, graft loss is excessive and underscores the need for more adequate immunosuppression.

Objective: To investigate risk factors for sensorineural hearing loss (SNHL) in children after liver transplantation., Design: Retrospective medical record review., Setting: Pediatric tertiary care hospital., Patients: One hundred twenty-five consecutive children who received liver transplants between March 1, 1987, and June 30, 1996., Main Outcome Measures: The presence of SNHL (bone conduction threshold of >35 dB of hearing loss in at least 1 frequency) and the cause of the liver abnormality in all 125 patients. In addition, among the subset of children who had biliary atresia and underwent transplantation before 2 years of age, the total dose (milligrams per kilogram of body weight) of aminoglycoside antibiotic medications (tobramycin sulfate, gentamicin sulfate, and amikacin sulfate) and of intravenous loop diuretic agents (furosemide) was compared between children with and without SNHL., Results: Audiologic evaluations were available for 66 of 125 patients, 15 (12%) of whom have SNHL. Of 5 survivors with the short-bowel syndrome, 4 have severe to profound SNHL. Of 46 children who have biliary atresia and who underwent transplantation before 2 years of age, 8 (17%) have SNHL. Among the 26 evaluable children with biliary atresia undergoing liver transplantation before 2 years of age, logistic regression analysis revealed that the most important risk factor for SNHL was the cumulative dose of amikacin (P = .05)., Conclusions: Children receiving liver transplants are at an increased risk for SNHL. Those with the short-bowel syndrome have the greatest prevalence of SNHL. Among the subset of children with biliary atresia receiving liver transplants before 2 years of age, statistical analysis demonstrates a dose-response relationship between the receipt of amikacin and the occurrence of SNHL.

Purpose: The aim of this review was to determine the incidence of gastrointestinal perforation after pediatric liver transplantation and to identify risk factors and clinical indicators that may lead to an earlier diagnosis., Methods: A retrospective chart review of all children who presented with gastrointestinal perforation after liver transplantation at our institution between January 1, 1987 and August 1, 1996 was performed., Results: One hundred fifty-seven orthotopic liver transplants were performed in 128 children. Fifty-eight reexplorations, excluding those for retransplantation, were performed in 38 children. Ten perforations occurred in six children (incidence, 6.4%). Two children required multiple reexplorations because of several episodes of perforation. The sites of perforation were duodenum (n=1), jejunum (n=8), and ileum (n=1). A single-layer closure was used to repair five perforations, two-layer closures in four, and resection with primary anastomosis in another. The type of repair did not affect the occurrence of subsequent perforations. All the children were less than 18 months old. Four children had undergone prior laparotomy. All children had choledochoenteric anastomoses, but only one had a perforation associated with it. One child sustained bowel injury during the dissection for the liver transplant, but none of the perforations occurred at this site. Bowel function had returned before perforation in five children. Five children were receiving systemic antibiotics at the time of their perforation, and none had been dosed with pulse steroids for rejection. All of the children had significant changes in their temperature. Acute leukopenia developed in one child. A leukocytosis developed in the rest of the children. Abdominal radiographs demonstrated pneumoperitoneum in only one child. All children had positive culture findings from their abdominal drains. Cytomegalovirus developed in one child. Although the diagnosis of gastrointestinal perforation after pediatric liver transplant remains difficult, positive drain culture findings and significant alterations in temperature and leukocyte counts suggest its presence. Pneumoperitoneum is rarely present., Conclusion: A high index of suspicion and timely laparotomy, especially in children less than 2 years of age, may be the only way to rapidly diagnose and treat this potentially devastating complication of liver transplant.

A randomized placebo-controlled trial was conducted to determine the benefit of ganciclovir (5 mg/[kg x d]) for 30 days in addition to intravenous immune globulin (IVIG) for 16 weeks for prevention of primary cytomegalovirus (CMV) disease in children receiving liver transplants. Patients were monitored for 6 months after transplantation. The two groups of patients (recipients of 29 ganciclovir plus IVIG and 27 recipients of IVIG alone) were similar in terms of age, sex, and underlying disease. The incidence of CMV disease among the ganciclovir plus IVIG recipients and the IVIG alone recipients was 17% and 26%, respectively, and the time to disease in these recipients was 46 days and 32 days, respectively. There was no difference between groups in terms of survival; episodes of rejection, bacteremia, or fungemia; use of immunosuppressive agents; and incidence of leukopenia or thrombocytopenia. These results suggest that a 4-week course of ganciclovir with IVIG is not more effective than IVIG alone for prevention of primary CMV disease. Since short-term prophylaxis with ganciclovir may delay the onset of CMV disease, further studies with a longer course of ganciclovir prophylaxis are warranted.

This case report correlates impaired cyclosporine absorption from the traditional oral formulation in a 9-year-old liver transplant recipient with subsequent acute allograft rejection. Although impaired absorption in this patient was documented by cyclosporine pharmacokinetic profiling (steady-state area under the cyclosporine concentration-time curve or AUC), no indication was evident from the pre-dose cyclosporine trough level, which was within the typical target range of blood concentrations. However, when the subject received the microemulsion formulation of cyclosporine the AUC value reflected an adequate absorption pattern. We recommend that if malabsorption is suspected in the de novo pediatric liver transplant patient, then single-sample pre-dose trough cyclosporine levels should not be relied on as an indicator of sufficient immunosuppression and that a limited sampling strategy be used to confirm or rule out impaired absorption.

Background: A comparison of the oral bioavailability of cyclosporine from the original formulation (CsA) and from the new formulation, cyclosporine for microemulsion (CsA-ME), was made in pediatric maintenance liver transplant patients within two age groups (group 1, ages 1-5 years; group 2, ages 6-17 years) in an open-label, multicenter, randomized crossover trial. All patients were at least 6 months past transplantation and were receiving CsA maintenance therapy., Methods: In study period 1 (days 1 through 14), patients were administered either CsA or CsA-ME at the same b.i.d. dosage as their maintenance therapy. Upon entry into period 2 (days 15 through 28), patients were converted to the alternate formulation at a 1:1 mg dose ratio. On day 29, all patients returned to the CsA treatment administered at study entry, with follow-up on day 35. Dosage adjustments were not allowed with either CsA or CsA-ME. Twelve-hour pharmacokinetic profiling was performed at the end of periods 1 and 2., Results: Both the mean area under the concentration-versus-time curve and the mean maximum blood concentration of cyclosporine-both normalized for dose-were significantly increased: by 66% and 109%, respectively, in patients receiving CsA-ME compared with those receiving CsA in group 1 and by 39% and 75%, respectively, in group 2. During this study, liver function remained stable, and serum creatinine and blood pressure did not differ significantly between treatment groups., Conclusions: This study shows increased bioavailability in all patients converted to CsA-ME, with the greatest increase seen in patients with the lowest initial cyclosporine bioavailability. The tolerability was similar between the two formulations during this study.

The division of a single hepatic allograft to create two reduced-size grafts has been reported with decreased graft survival (50%) resulting in decreased enthusiasm for this approach. The authors reviewed their experience with 12 recipients of this procedure to evaluate the outcome of the children electively undergoing transplant with the "leftover liver." A retrospective review of six pairs of children receiving part of one hepatic allograft included donor anatomy, recipient operation, and allograft and patient outcomes. Recipient pairs were selected according to blood type compatibility, medical priority, and size restrictions of the larger right lobe and the smaller left lateral segment. Patient and graft survival were compared with elective and urgent patients undergoing whole or reduced-size transplants. Six donors weighed 71.8 +/- 17.4 kg and were 22.6 +/- 11.0 years of age. Recipients of the right lobe were 11.8 +/- 4.2 years of age and weighed 41.9 +/- 14 kg. Recipients of the left lateral segment were 1.81 +/- 1.1 years of age and weighed 9.85 +/- 1.82 kg. Six patients were initially offered the donor allograft because of their hospitalization, critical illness or waiting time. Six additional patients electively underwent transplantation with the leftover liver. Donor organs were screened for normal arterial anatomy. Division of the allograft was performed on the back table in the falciform groove. Generally the left lateral segment graft received the major portion of the hepatic artery and the right lobe the major portion of the portal vein. Five of six (83%) elective patients, two receiving the right lobe and three receiving the left lateral segment had prompt recovery and left the hospital without surgical complication. One recipient of a right lobe transplant died from primary allograft nonfunction. These results are not different from the outcomes of all elective patients who underwent transplantation with whole or reduced-sized transplants in the same program. The authors conclude that split liver transplantation benefits the stable patient who electively receives the liver leftover after reducing the size of a large donor liver for a critically ill child.

Veno-occlusive disease (VOD) is the third leading cause of mortality after bone marrow transplant. Management consists of supportive care, with restricted fluids and diuretics. Most patients will recover, but approximately 25% may develop severe life threatening VOD with subsequent respiratory compromise and multiorgan failure. Orthotopic liver transplant has been attempted for a few patients with intractable VOD, but this approach is limited by availability of a cadaveric organ. We report a child who underwent a T-depleted unrelated donor bone marrow transplant for severe aplastic anemia as a manifestation of Schwachman-Diamond syndrome who developed severe VOD. She had evidence of engraftment when liver transplant was considered, and had no evidence of major organ dysfunction. The left lateral segment of her mother's liver was transplanted at day +33 following bone marrow transplantation. The child remains well ten months post-BMT and nine months after liver transplant. A related donor liver transplant may be a justifiable approach in a patient with severe VOD post-BMT.

In pediatric liver transplant recipients, oral cyclosporine (CsA) therapy may be complicated by impaired or delayed absorption during the initial weeks posttransplant. Neoral (NL) is a microemulsion preconcentrate formulation of CsA expected to increase the rate and extent of absorption of CsA and have less pharmacokinetic variability. The absolute bioavailability (F) of CsA from NL was compared with that of the currently marketed Sandimmune (SM) formulation in a double-blind, crossover study conducted in 9 pediatric liver transplant recipients (age 6 months to 11 years) between 8 and 20 days posttransplant. After determination of CsA pharmacokinetics for a steady-state intravenous dose, patients were randomized to receive a single oral dose of NL or SM in period I and the alternative formulation in period II. Clearance (Clt) and volume of distribution (Vss) values (mean +/- s.d.) calculated from the i.v. dose were similar to that previously reported for pediatric patients (Clt = 12.0 +/- 1.3 ml/min/kg; Vss = 2.2 +/- 0.2 L/kg). Mean F (+/- SD) for NL was significantly higher than SM (NL = 37.6 +/- 14.6%; SM = 24.7 +/- 8.0%; P = 0.05). Although not reaching statistical significance, the observed maximum blood concentration (Cmax) was higher, and the time to Cmax (Tmax) was shorter for NL in 8 or 9 patients. There were no significant correlations between age and any pharmacokinetic parameter for the group as a whole--however, there were statistically significant correlations between age and F for NL (r = 0.87; P = 0.02), and for age and Vss (r = 0.91; P = 0.01) for the 6 patients aged 2 years or less. In this pediatric liver transplant population, Neoral demonstrated improved absorption (% increase in F) compared to Sandimmune. In liver transplant recipients aged 2 years or less, absorption of Neoral may be a function of age and/or bowel length.

Liver transplantation became a very successful therapy when cyclosporin A was introduced as an immunosuppressive agent. In an effort to evaluate the contribution of difficult or uncontrolled allograft rejection to mortality, the authors determined the most important factors that limited survival after liver transplantation. Eighty-two children received a total of 94 liver transplants from January 1987 to the present. Patients' records were reviewed for complications that contributed to morbidity and mortality and to assess which complications were preventable. Twelve patients died (15%), nine within 6 weeks of liver transplantation. The chief contributing cause of death was hepatic artery thrombosis (one patient), brain death after liver transplantation for fulminant hepatic failure (two patients), primary allograft nonfunction or dysfunction (two patients), allograft rejection (three patients), or other problems (four patients). Overall, hepatic artery thrombosis occurred in 3.1%, allograft rejection in 57%, fulminant hepatic failure in 7%, and donor organ dysfunction in 7%. Allograft rejection contributed directly to the cause of death in three children (4%). The authors conclude that few deaths after pediatric liver transplantation are caused by failure of immunosuppression. A high survival rate can be achieved after transplantation by eliminating the correctable complications that most frequently occur in the early postoperative period.

The ultimate prognosis for patients with short bowel syndrome (SBS) has become progressively more favorable over the past decade. Advances in long-term total parenteral nutrition (TPN) have allowed this group of patients to meet nutritional needs while the process of intestinal adaptation occurs. Unfortunately, a subgroup of patients with SBS have hepatic failure (HF), most often secondary to TPN-induced cholestasis. Combined small bowel and liver transplantation (LT) offers a sound anatomic solution for cases of HF with SGS, but it remains experimental at this time. We propose that an isolated LT is a viable alternative mode of therapy for the patient with HF and SBS. The following characteristics were reviewed for five patients with SBS and HF who underwent LT: age at transplantation, weight, liver function, survival, intestinal length, volume of feeding before surgery, and current feeding tolerance and liver function. Four boys and one girl, aged 5.5 to 15 months (average, 11.9), had LT. The total bilirubin level at the time of transplantation was 14.4 to 37 mg/dL (average, 24.7). The patients weighed between 3.8 and 12 kg (average, 8.0), and feeding tolerance ranged from no enteric to complete enteric feeding (average, < 33% of calories by enteric feeding). Bowel loss was attributed to necrotizing enterocolitis in two cases, volvulus in two, and birth hypoxia in one. Bowel length ranged from 60 to 120 cm (average, 88.6). Four children (80%) survived LT, and the average follow-up period was 9.3 months. Three (75%) are home; one is on combined hyperalimentation and enteral feeding, and two are on full enteric feeding. One remains in a chronic care facility, on combined enteral and intravenous feeding. The average daily enteral feeding now comprises more than 70% of caloric requirements. The total bilirubin level is .6 to .8 mg/dL (average, .71). Isolated LT for HF in the patient with SBS effectively restores liver function, allowing time for further intestinal adaptation.

Children who survive liver transplantation (LT) suffer the adverse effects of life-long immunosuppression. In an attempt to minimize these effects, we have instituted a program of tapering immunosuppression, resulting in chronic monotherapy for children after LT. Seventy-three children ages 4 months to 19 years received LT between January 1987 and December 1992. Patient survival was 85% (62/73), with graft survival of 73%, at one year. Triple therapy with prednisone, cyclosporine, and azathioprine begun at transplant was tapered as follows: 1-2 mg/kg prednisone at discharge was reduced by .2 mg/kg every 2 months until a .2 mg/kg total was reached. Alternate-day steroids (.2 mg/kg) were begun at 1 year and discontinued at 1.5 years. AZA (1 mg/kg) was begun posttransplant and discontinued after any serious viral illness or by 1 year. Currently 37 survivors are > 18 months post-LT and were considered candidates for monotherapy. Monotherapy was attempted in 28 (76%), and 25 of these remain on monotherapy an average of 2 years later. All have normal liver function. After monotherapy and alternate-day steroids were achieved, 66% of children < 5th percentile for height at the time of transplant improved to greater than the 5th percentile. There were 3 (11%) patients who rejected while on monotherapy an average of 1.15 years after it was started. These patients had the following predisposing factors that decreased cyclosporine levels and led to rejection: common bile duct stricture, chronic and intermittent antibiotic administration for urinary tract infection, and noncompliance. In the 9 potential candidates not tapered to monotherapy, 6 have had recurrent acute or chronic rejection; 2 of these now receive FK506. We conclude that the majority of stable pediatric LT recipients may be safely tapered to chronic cyclosporine monotherapy. Increased growth is a major benefit of decreased steroid dosing in these children. Cyclosporine absorption and adequate levels are crucial for success of this approach.

The authors report the first case of orthotopic liver transplantation in a pediatric patient in whom packed red blood cell transfusion was not required. This has obvious advantages in avoiding the infectious complications of transfusion. Our patient required 3 U of fresh frozen plasma for treatment of preexisting coagulopathy. However, it is possible that, with future advances in transfusion therapy, synthetic coagulation factors may be provided in which there is no risk of infectious complications, and therefore a truly "bloodless" orthotopic liver transplant can be performed.

The aim of this study was to determine if age less than 1 year is a high risk group for orthotopic liver transplantation (OLT). Retrospective analysis was done of patients with liver failure who received OLT. Comparison was made between patients aged < 1 year and > 1 year with regard to survival, allograft survival, hepatic artery thrombosis, and medical status at OLT. Between January 1, 1987 and September 30, 1991, 46 children received OLT. Fifteen (35%) were < 1 year (average age, 7.93 months). Survival in children < 1 year was 80% and children > 1 year was 91%. Allograft survival in children < 1 year was 57% (21 allografts required for 12 survivors) and 78% in children > 1 year (37 allografts required for 29 survivors). Retransplantation was required in 5 of 15 children < 1 year (33%) and in 5 of 29 children (17%) > 1 year. Medical status in children < 1 year was similar to medical status in children > 1 year at the time of transplant. Children with chronic stable liver disease represented 60% of children < 1 year and 60.1% of children > 1 year. Children requiring hospitalization represented 26% of children < 1 year and 29% of children > 1 year. Children in intensive care represented 13% of children < 1 year and 11% of children > 1 year. Survival for all status groups was similar. Hepatic artery thrombosis occurred in one child < 1 year and in 2 children > 1 year. No statistical difference (chi 2 analysis) was found by age between the categories evaluated.(ABSTRACT TRUNCATED AT 250 WORDS)

A 3.5-year-old boy presented with end-stage renal disease and bilateral nephrocalcinosis. Renal biopsy demonstrated marked parenchymal calcium oxalate deposition and a diagnosis of primary hyperoxaluria (PH) was made. Following 2 years of hemodialysis he received two renal allografts which were lost at 7 and 11 months, respectively, due to biopsy-proven recurrent oxalosis. Combined liver-kidney transplantation was then performed, after which renal and hepatic function initially stabilized. The patient died on the 28th postoperative day, of infectious complications and progressive respiratory insufficiency. However, comparisons between the patterns of urinary oxalate excretion noted after the isolated renal and liver-kidney transplants indicated that, following the latter, successful biochemical correction of the enzyme defect responsible for type 1 PH had occurred.

Background: SPLIT was founded in 1995 in order to collect comprehensive prospective data on pediatric liver transplantation, including waiting list data, transplant, and early and late outcomes. Since 2011, data collection of the current registry has been refined to focus on prospective data and outcomes only after transplant to serve as a foundation for the future development of targeted clinical studies. Objective: To report the outcomes of the SPLIT registry from 2011 to 2018. Methods: This is a multicenter, cross‐sectional analysis characterizing patients transplanted and enrolled in the SPLIT registry between 2011 and 2018. All patients, <18 years of age, received a first liver‐only, a combined liver‐kidney, or a combined liver‐pancreas transplant during this study period. Results: A total of 1911 recipients from 39 participating centers in North America were registered. Indications included biliary atresia (38.5%), metabolic disease (19.1%), tumors (11.7%), and fulminant liver failure (11.5%). Greater than 50% of recipients were transplanted as either Status 1A/1B or with a MELD/PELD exception score. Incompatible transplants were performed in 4.1%. Kaplan‐Meier estimates of 1‐year patient and graft survival were 97.3% and 96.6%. First 30 days of surgical complications included reoperation (31.7%), hepatic artery thrombosis (6.3%), and portal vein thrombosis (3.2%). In the first 90 days, biliary tract complications were reported in 13.6%. Acute cellular rejection during first year was 34.7%. At 1 and 2 years of follow‐up, 39.2% and 50.6% had normal liver tests on monotherapy (tacrolimus or sirolimus). Further surgical, survival, allograft function, and complications are detailed. [ABSTRACT FROM AUTHOR]