Outcomes of liver transplantation in pediatric recipients with cardiovascular disease.

LT exerts considerable stress on the heart perioperatively. Limited data exist on impact of cardiovascular diseases on LT children. This study evaluated the outcomes of children with CVD who underwent LT and compared with pretransplant findings. From 518 LT recipients, 82 (15.8%) had CVD. Sixty patients were classified as low-risk adjustment for congenital heart surgery 1 (RACHS 1 and 2). Five patients were classified as RACHS ≥3. The most common echocardiographic finding in the CVD patients (25/82) was ASD. CVD patients had more abnormal EKG (32.4% vs 14.5%, P < .001), abnormal chest X-ray (11.8% vs 1.4%, P < .001), and altered echocardiography (89.7% vs 15.4%, P < .001) findings compared with the No-CVD group pretransplant. Post-transplant, significant differences between groups were observed related to abnormal EKG (14.7% vs 7.0%, P = .03) and echocardiography (48.5% vs 3.2%, P < .01) findings. Pretransplant ASD spontaneously closed in 22 patients. At 1 and 5 years post-transplant, there was no difference in the survival rate between groups (P = .96). The prevalence of CVD in recipients of LT was high, and its presence was associated with significantly higher cardiac decompensation before and after LT. Minor and moderate cardiovascular disease did not impact the long-term survival.

Living donor liver transplantation for neonatal fulminant hepatitis due to herpes simplex virus infection.

Although rare, ALF caused by disseminated HSV infection is associated with high mortality in the neonatal population. This condition is often diagnosed relatively late due to the absence of specific signs. We present a case involving a neonate with ALF submitted to living donor liver transplantation without a prior diagnosis. The patient had no skin or mucosal lesions, and IgM serology was negative for HSV-1 and HSV-2. Immunohistochemical staining of the liver explant was positive for herpes virus infection, and the patient subsequently received antiviral drug treatment, with a good outcome. Due to organ shortages and the rarity of the aforementioned condition, LT has seldom been reported for the treatment of ALF caused by herpes virus infection; however, LT may be the only option for neonates with fulminant hepatitis. The use of living donors in an urgent scenario is well established in Eastern countries and safely applicable for pediatric patients with ALF.

Pancreas-preserving duodenectomy after living donor liver transplantation for invasive cytomegalovirus disease.

CMV infection plays an important role in the postoperative course following solid organ transplantation. We present the case of an 11-year-old male patient who underwent LDLT due to severe hepatopulmonary syndrome and biliary cirrhosis. Four weeks after LDLT, he developed persistent GI bleeding and was subjected to repeated endoscopic treatment and radiological arterial embolization to stop the bleeding from duodenal ulcers. Diagnostic workup was negative for CMV disease. Because the bleeding persisted, surgical treatment was indicated, and a pancreas-preserving duodenectomy was performed. Immunohistochemical staining of the surgical specimen demonstrated diffuse endothelial infiltration by CMV. Despite ganciclovir treatment, the patient developed new erosions in the jejunal mucosa and melena; ganciclovir was discontinued, and foscarnet was started, resulting in clinical improvement and the cessation of bleeding. This case highlights the technical aspects of performing a complex upper GI resection in a patient recently subjected to LDLT, taking care to avoid injury to the previous liver graft anastomosis and restore GI continuity. Moreover, CMV tissue-invasive disease compartmentalized in the GI tract may be difficult to diagnose, as indicated by the negative results of antigenemia and PCR assays and endoscopic superficial mucosal biopsies.

Simultaneous or sequential gastrectomy in pediatric liver transplant recipients.

The association between LT and gastrectomy is not common. Only two studies reported the gastrectomy/LT association in children. Here, we report three children who underwent LT who required a concomitant or sequential gastrectomy for different reasons. Patient 1, a 16-yr-old boy, during the LT, underwent a partial gastrectomy due to extensive injury to the duodenum. He had a previous and unusual portoenterostomy performed in the duodenum. Bowel reconstruction was performed using an intestinal loop that was first used for the bilio-enteric anastomosis and then connected to the gastric stump. Patient 2, a 22-month-old female child, underwent a partial gastrectomy with a Roux-en-Y reconstruction during a retransplantation. She had a large perforated gastric ulcer blocked by the allograft liver. Patient 3, a 26-month-old male child, five yr after living donor LT, was submitted to a partial gastrectomy because of gastric outlet obstruction. The histopathology was compatible with eosinophilic gastritis. The association between LT and gastrectomy in the pediatric population is extremely rare. Appropriate knowledge of the previous transplantation technique is very important. Further studies are required to assess the outcomes of the different types of gastric reconstruction in pediatric recipients.

Alternatives for vascular reconstruction in pediatric living donor liver transplantation.

Many publications discuss the various strategies for vascular reconstruction (VR) in pediatric LDLT. Having knowledge of alternative techniques is helpful in planning transplants. This article presents three case reports that illustrate some of the alternative techniques for HV, PV, and HA reconstruction in pediatric LDLT. It also reviews the available alternative strategies reported for VR in pediatric LDLT. In the first case, a 13-month-old girl presented a PRETEXT III HB with invasion of the retrohepatic vena cava. An LLS graft HV was anastomosed to a DD iliac vein graft and subsequently implanted in a "standard" fashion in the recipient. In the second case, a 44-month-old boy presented with multifocal HB and portomesenteric thrombosis and the portal inflow was done through a renoportal anastomosis. In the third case, a 22-month-old child with a failed Kasai procedure had extensive HA thrombosis. The HA reconstruction was performed with an interposition of the recipient's IMV graft. The use of alternative techniques for VR in pediatric LDLT is paramount to the success of such a complex procedure. Imaging studies can help transplant surgeons outline surgical strategies and define the best technique to be used in each case.

Outcomes and technical aspects of liver retransplantation with living donors in children.

Re-LT is the only recourse for patients with liver graft failure. However, survival rates after re-LT are lower than those of primary transplants. Few reports are available regarding re-LT with LDs in children. The objective of this study was to describe our cohort of patients retransplanted with LD and emphasize the technical aspects of a re-LT with LD. This is a retrospective report of a series of 18 children (<18 yr old) submitted to 20 re-LT from January 1997 to December 2013 at Hospital Sirio-Libanes and Hospital AC Camargo Cancer Center. The one- and five-yr survival for patients retransplanted with LD was 70.6% and 58.6%. Little technical modifications from a regular LD primary transplant were needed in patients retransplanted with LD. Seven (38.8%) patients presented vascular complications following re-LT and three presented biliary complications (16.6%). In conclusion, a re-LT with LD is an acceptable alternative for children who experience liver graft failure and it does not compromise the donor pool. Further experience with re-LT with LD may support this therapy.

Impact of Kasai portoenterostomy on liver transplantation outcomes: A retrospective cohort study of 347 children with biliary atresia.

Biliary atresia (BA) is the main diagnosis leading to liver transplantation (LT) in children. When diagnosed early in life, a Kasai portoenterostomy (Kasai-PE) can prevent or postpone LT. Instances of previous operations can result in difficulties during the LT. We hypothesized that a previous Kasai-PE could affect LT outcomes. A retrospective cohort study of 347 BA patients submitted to LT between 1995 and 2013 at Hospital Sírio-Libanês and A. C. Camargo Cancer Center was conducted. Patients were divided into those with a previous Kasai portoenterostomy early failure (K-EF), Kasai portoenterostomy late failure (K-LF), and those with no Kasai portoenterostomy (No-K). Primary outcomes were patient and graft survival. A total of 94 (27.1%) patients had a K-EF, 115 (33.1%) had a K-LF, and 138 (39.8%) had No-K before LT. Children in the K-LF group were older and had lower Pediatric End-Stage Liver Disease (PELD) scores. Patients in both K-EF and K-LF groups had more post-LT biliary complications. After Cox-multivariate analysis adjusting for confounding factors to determine the influence of Kasai-PE on patient and graft survival, the K-LF group had an 84% less probability of dying and a 55% less chance to undergo retransplantation. The K-LF group had a protective effect on posttransplant patient and graft survival. When properly performed, the Kasai procedure can postpone LT and positively affect outcomes. Having a K-EF and having not performed a Kasai-PE had the same effect in patient and graft survival; however, a previous Kasai-PE can increase post-LT complications as biliary complications and bowel perforations.

Ascites and serum sodium are markers of increased waiting list mortality in children with chronic liver failure.

UNLABELLED: Ascites is the most common complication of cirrhosis and in adults it is associated with 50% mortality at 5 years if patients do not receive a liver transplant. The occurrence of hyponatremia in these patients has been associated with increased mortality on the waiting list. The importance of serum sodium levels and the presence of ascites in the pediatric setting remain to be clarified. A retrospective analysis of pediatric patients with cirrhosis on the transplant list was carried out between October 2000 and February 2012. The primary objective of this study was to evaluate the association of pretransplant variables with mortality within 90 days following the inclusion of patients on the waiting list. In all, 522 patients were included in the study; 345 (66%) patients were under 1 year of age; 208 (40%) of the children presented ascites. A multivariate Cox proportional hazards analysis was conducted and total bilirubin (P < 0.001, hazard ratio [HR] = 2.09, 95% confidence interval [CI] = 1.35-3.21), international normalized ratio (INR) (P < 0.001, HR = 9.83, 95% CI = 4.51-21.45), serum sodium levels (P = 0.03, HR = 0.96, 95% CI = 0.92-0.99), ascites (P = 0.001, HR = 2.59, 95% CI = 1.44-4.64), and categorized age (0-1 versus ≥ 1 year old) (P = 0.025, HR = 2.33, 95% CI = 1.11-4.86) were independently associated with risk of death in 90 days. Malnutrition (Z score height/age, weight/age) and serum albumin (pediatric endstage liver disease [PELD] formula) were not included in the final model. CONCLUSION: The presence of ascites and serum sodium levels are important variables associated with decreased patient survival while candidates wait for a liver graft. Multicenter studies are necessary to validate these findings in order to improve current allocation policies based on the PELD score.

Analysis of factors associated with portal vein thrombosis in pediatric living donor liver transplant recipients.

The technique of vascular reconstruction plays a major role in the outcome of living donor liver transplantation (LDLT). An increased use of vascular grafts (VGs) as replacements for sclerotic portal veins has become a standard technique for our group. The aim of this study was to analyze the factors associated with portal vein thrombosis (PVT) in pediatric LDLT. We performed a retrospective analysis of 486 primary pediatric LDLT procedures performed between October 1995 and May 2013. VGs used for portal reconstruction included living donor inferior mesenteric veins, living donor ovarian veins, recipient internal jugular veins, deceased donor iliac arteries, and deceased donor iliac veins. Thirty-four patients (7.0%) developed PVT. The incidence of PVT dropped from 10.1% to 2%; the overall utilization of VGs increased from 3.5% to 37.1%. In a multivariate analysis, only the use of VGs remained an independent risk factor for the occurrence of PVT (hazard ratio = 7.2, 95% confidence interval = 2.8-18.7, P < 0.001). There was no difference in survival rates between patients with PVT and patients without PVT. No patient with PVT underwent retransplantation. In conclusion, the use of VGs was independently associated with the development of PVT. Over time, there was a reduction in the incidence of early PVT in this cohort, and there was a trend toward a reduction in total PVT. The occurrence of isolated PVT in this study was not associated with decreased patient or graft survival.

Diagnosis and management of biliary complications in pediatric living donor liver transplant recipients.

The incidence of biliary complications (BCs) after living donor liver transplantation (LDLT) can reach 40%. Published data on the pediatric population are limited, and treatment protocols vary. Our aim was to describe the clinical scenario for BCs and treatment approaches after LDLT. Between October 1995 and December 2012, 489 pediatric LDLT procedures were performed. BCs developed in 71 patients (14.5%). Biliary strictures (BSs) developed in 45 (9.2%) patients, and bile leaks (BLs) developed in 33 patients (6.7%). The BL diagnosis was clinical in all cases, and 69.7% of the patients underwent surgery. Nearly half of the BS cases had clinical features or suggestive ultrasound findings. Liver biopsy findings suggested BSs in 51.7%. Percutaneous transhepatic cholangiography was performed in 95.6% of the BS patients. The success rate was 77% [mean number of percutaneous biliary interventions (PBIs) = 3.9 ± 1.98, median drainage time = 8 months]. In conclusion, BL patients can be managed with conservative therapy, even though most of these patients will ultimately be treated with surgery. Diagnosing a BS requires a high degree of clinical suspicion because the available resources for its identification can fail in up to 50% of cases. A higher number of PBIs and the use of a drainage catheter for a longer time may be required to achieve better results with this technique.

Technical aspects and outcomes of living donor liver transplantation for pediatric patients with situs inversus.

The vascular anomalies encountered in patients with biliary atresia associated with polysplenia syndrome and situs inversus (SI) demand technical refinements when liver transplantation is being performed. The available data describing the technique used in living donor liver transplantation (LDLT) in this population are limited; the short vascular stumps of the donor's liver can impart additional technical difficulties during vascular reconstruction. Here we describe our experience with 9 children with biliary atresia and SI who underwent LDLT. In our series, the retrohepatic vena cava was absent for 7 patients, 7 had a preduodenal portal vein (PV), and 4 had a variant arterial anatomy. The donor's left hepatic vein was anastomosed to the confluence of the recipient's 3 hepatic veins in 7 patients. Vascular grafts were used for PV reconstruction in 3 cases. A left lateral segment graft was used in all but 1 patient who needed a graft reduction. All grafts were placed in the upper left abdomen. There were no vascular complications after transplantation. All patients were alive and well at a median follow-up of 55 months. In conclusion, LDLT can be successfully performed in pediatric patients with SI. Complex vascular anomalies associated with the use of partial liver grafts obtained from living donors are not associated with an increased occurrence of vascular complications.

Liver transplantation after stage II palliation for hypoplastic left heart syndrome.

The association of biliary atresia (BA) with congenital heart diseases has been extensively described, and there are a number of reports on the outcomes of patients in this group who undergo liver transplantation (LT). The intraoperative management and the timing of LT for patients with end-stage liver disease are matters of debate, especially when complex heart diseases are involved. This report describes the outcome after LT for a pediatric recipient with BA and hypoplastic left heart syndrome. The patient underwent Norwood-Sano and Glenn procedures for heart palliation before LT. He was cyanotic, was severely malnourished, and had complications secondary to chronic liver failure. At the time of transplantation, the child was 16 months old and weighed 5175 g. Despite the critical clinical scenario and the long hospitalization period, there were no cardiac, vascular, or biliary complications after LT. At the age of 48 months, the patient was awaiting the final cardiac repair. In conclusion, the presence of complex cardiac malformations may not be a contraindication to LT. An experienced surgical team and a multidisciplinary approach are key to a successful outcome.

Four hundred thirty consecutive pediatric living donor liver transplants: variables associated with posttransplant patient and graft survival.

The availability of living donors allows transplant teams to indicate living donor liver transplantation (LDLT) early in the course of liver disease before the occurrence of life-threatening complications. Late referral to transplant centers is still a problem and can compromise the success of the procedure. The aim of this study was to examine the perioperative factors associated with patient and graft survival for 430 consecutive pediatric LDLT procedures at Sirio-Libanes Hospital/A. C. Camargo Hospital (São Paulo, Brazil) between October 1995 and April 2011. The studied pretransplant variables included the following: recipient age and body weight, Pediatric End-Stage Liver Disease score, z score for height/age, bilirubin, albumin, international normalized ratio, hemoglobin, sodium, presence of ascites, and previous surgery. The analyzed technical aspects included the graft-to-recipient weight ratio and the use of vascular grafts for portal vein reconstruction. In addition, the occurrence of hepatic artery thrombosis (HAT), portal vein thrombosis (PVT), and biliary complications was also analyzed. The liver grafts included 348 left lateral segments, 5 monosegments, 51 left lobes, and 9 right lobes. In a univariate analysis, an age < 12 months, a low body weight (≤10 kg), malnutrition, hyperbilirubinemia, and HAT were associated with decreased patient and graft survival after LDLT. In a multivariate analysis, a body weight ≤ 10 kg and HAT were significantly associated with decreased patient and graft survival. The use of vascular grafts significantly increased the occurrence of PVT. In conclusion, a low body weight (≤10 kg) and the occurrence of HAT independently determined worse patient and graft survival in this large cohort of pediatric LDLT patients.

Living Donor Liver Transplantation as a Backup Procedure: Treatment Strategy for Hepatocellular Adenomas Requiring Complex Resections.

METHODS: We present a series of three patients with large hepatocellular adenoma lesions showing a central location, for which the living donor liver transplantation strategy was used as a backup procedure. RESULTS: Hepatocellular adenoma was confirmed by biopsy in all patients. Surgical resection was indicated because of the patients' symptoms and lesion size and growth. All patients had a lesion that was central or in close contact with major vessels. The final decision to proceed with the resection was made intraoperatively. A live donor was prepared for all three patients. Two patients underwent portal vein embolization associated with extended hepatectomy, and a total hepatectomy plus liver transplantation with a living donor was performed in one patient. All patients had good postoperative outcomes. CONCLUSIONS: In the treatment of hepatocellular adenomas for which complex resections are necessary and resectability can only be confirmed intraoperatively, surgical safety can be improved through the use of a living donor backup. Center expertise with living donor liver transplantation is paramount for the success of this approach.

Schistosoma mansoni infection in the liver graft: The impact on donor and recipient outcomes after transplantation.

The increasing number of transplants performed each year has led to the identification of unusual diseases in liver grafts from asymptomatic donors that were unrecognized before liver transplantation. Here we report our experience with patients who received liver grafts infected with schistosomiasis. From September 1991 to August 2010, 482 pediatric liver transplants were performed at A. C. Camargo Hospital/Sírio-Libanês Hospital (São Paulo, Brazil). For the identification of Schistosoma mansoni infections, pathology slides for the recipients were reviewed; these included postreperfusion and follow-up liver biopsy samples. We were able to identify 6 cases of schistosomiasis transmitted through infected grafts (5 of these grafts were from living donors). All living donors were confirmed to have normal liver chemistries, negative fecal tests for parasitic diseases, and normal abdominal ultrasound findings. Liver biopsy was not performed before transplantation. In all cases, features of schistosomiasis were absent in the liver explants. The living donors were treated with praziquantel and were taught to avoid risk factors for reinfection. No specific treatment for schistosomiasis was given to the recipients. There were no perioperative deaths, but 2 recipients died after living donor liver transplantation (LDLT) because of Kaposi's sarcoma and non-Hodgkin's lymphoma. In conclusion, using liver grafts infected with S. mansoni eggs did not compromise the results of LDLT in this pediatric cohort. Because of the parasite's life cycle and the therapeutic target of praziquantel, only donors should be treated for the infection. Three years of follow-up showed an uneventful recovery for the living donors.

Analysis of Factors Associated With Biliary Complications in Children After Liver Transplantation.

BACKGROUND: Biliary complications (BCs) remain an important cause of morbidity after pediatric liver transplantation. Technical factors have already been implicated in the development of BCs. Previous reports have associated the use of partial grafts, particularly living donor grafts, with a higher incidence of BCs. Our aim is to study the factors associated with the development of BCs in a large cohort of pediatric liver transplant recipients. METHODS: Retrospective cohort study of 670 children (<18 years of age) who underwent a primary liver transplant between March 2000 and January 2015. Patients who did and did not develop BCs were compared with identify associated factors. Univariate and multivariate analyses were performed. RESULTS: A total of 115 patients (17.2%) developed BCs (83 strictures and 44 leaks). Of the study participants, 594 had living donor liver transplants. Multiple arterial anastomoses was a protective factor for BCs, and a ductoplasty was a risk factor. Living donor grafts and multiple biliary anastomoses were more frequently associated with leaks. Patients with BCs had a higher reoperation rate and longer hospital stays. There was no difference in patient or graft survival. CONCLUSIONS: Technical factors play a major role in the development of BCs, particularly leaks. Strictures are more frequently associated with an inadequate arterial supply to the bile duct, and multiple arterial anastomoses may protect children from this complication. The use of partial grafts was not an independent factor for BCs in high-volume centers that are experienced with this technique.

Twenty Years of Experience in Pediatric Living Donor Liver Transplantation: Focus on Hepatic Artery Reconstruction, Complications, and Outcomes.

BACKGROUND: Hepatic artery thrombosis (HAT) increases morbidity and mortality after liver transplantation (LT). The identification of risk factors for HAT may aid transplant teams in the development of strategies aimed at reducing HAT. This article describes the risk factors for HAT and outcomes after LT. METHODS: This report describes a retrospective study (1995 to 2015) of primary pediatric living donor LT (LDLT). Pretransplant and technical variables were included in the study. Binary logistic regression was used for data analysis. RESULTS: This study included 656 primary LDLT. The median age, body weight, and pediatric end-stage liver disease score at the time of transplant were 13 months, 8.4 kg and 15, respectively. Twenty-one (3.2%) patients developed HAT. Intraoperative HAT (odds ratio, 62.63; 95% confidence interval, 12.64-310.19; P < 0.001) and the use of liver grafts with a graft-to-recipient weight ratio less than 1.1% (odds ratio, 24.46; 95% confidence interval, 4.55-131.56; P < 0.001) retained statistical significance in the multivariate model. Patient and graft survivals were significantly worse in cases with HAT. The overtime trend analysis revealed a decrease in the incidence of HAT (P = 0.008) and an increase in the use of 2-arterial anastomosis (P < 0.001). CONCLUSIONS: A graft-to-recipient weight ratio of 1.1% or less and intraoperative HAT were independently associated with HAT. Trend analysis further revealed a significant reduction in the incidence of HAT over time, as well as the increased use of 2 hepatic arteries for anastomosis during graft implantation. The double artery anastomosis may represent an extra protection to pediatric recipients undergoing LDLT.

Risk Factors Associated with Increased Morbidity in Living Liver Donation.

Living donor liver donation (LDLD) is an alternative to cadaveric liver donation. We aimed at identifying risk factors and developing a score for prediction of postoperative complications (POCs) after LDLD in donors. This is a retrospective cohort study in 688 donors between June 1995 and February 2014 at Hospital Sírio-Libanês and A.C. Camargo Cancer Center, in São Paulo, Brazil. Primary outcome was POC graded ≥III according to the Clavien-Dindo classification. Left lateral segment (LLS), left lobe (LL), and right lobe resections (RL) were conducted in 492 (71.4%), 109 (15.8%), and 87 (12.6%) donors, respectively. In total, 43 (6.2%) developed POCs, which were more common after RL than LLS and LL (14/87 (16.1%) versus 23/492 (4.5%) and 6/109 (5.5%), resp., p < 0.001). Multivariate analysis showed that RL resection (OR: 2.81, 95% CI: 1.32 to 3.01; p = 0.008), smoking status (OR: 3.2, 95% CI: 1.35 to 7.56; p = 0.012), and blood transfusion (OR: 3.15, 95% CI: 1.45 to 6.84; p = 0.004) were independently associated with POCs. RL resection, intraoperative blood transfusion, and smoking were associated with increased risk for POCs in donors.

Transplante de fígado intervivos em criança com falência hepática fulminante: Primeiro caso do Norte/Nordeste do Brasil / Adult-to-child living donor liver transplantation for fulminant hepatic failure: First report from Northeast of Brazil

Nos últimos anos houve importante aumento no número de transplante de fígado, indicados pra tratar hepatite aguda ou subaguda. Essas doenças representam significante parcela do total de transplantes de fígado realizados nos principais centros de transplante de fígado do mundo. Os autores descrevem o primeiro caso do Norte-Nordeste do Brasil de transplante de fígado a partir de doador vivo indicado para tratar hepatite fulminante