Mean Pediatric End-stage Liver Disease Research Articles

Pediatric liver transplantation for autoimmune liver disease: Ten-year experience from a liver transplant center in India.

Liver transplantation (LT) has emerged as the best therapeutic modality for end-stage liver disease in pediatric autoimmune liver disease (AILD). We aimed to describe our experience of pediatric living donor liver transplantation for AILD from India over a period of 10 years.We did a retrospective analysis of 244 liver transplants at our center over the last 10 years to identify children with AILD (18 years or younger). We aimed to describe the demographic features, clinical profile, graft survival, patient outcome, and predictors of mortality in our cohort.Between July 2010 and May 2020, 13 liver transplants were performed for AILD out of total 244 children transplanted over the last 10 years at our center. Mean (standard deviation [SD]) age at LT was 12 (± 3.84) years. Leading indications for LT were decompensated liver disease (61.5%), acute-on-chronic liver failure (23.1%), acute liver failure (ALF) (7.7%), and recurrent cholangitis and growth failure (7.7%). Mean Pediatric End-stage Liver Disease (PELD) score/model for end-stage liver disease (MELD) score and international normalized ratio (INR) (SD) at presentation were 24 (± 12.81) and 2.48 (± 1.54), respectively. Median discharge duration was 23 days (interquartile range [IQR] 21-36 days). 30.7% (4/13) of the subjects had no postoperative complications. Diarrhea (15.3%), pneumonia (7.7%), jejunostomy site bleed (7.7%), tacrolimus toxicity (7.7%), and vascular complications (7.7%) were seen, which resolved with satisfactory graft function. Three subjects died post-LT; causes of death included sepsis (n=3), renal dysfunction (n=1), and pneumonia (n=1). Others have been well on follow-up with no graft rejection or need for re-transplantation. Overall, 1-year and 5-year patient survival rates were 76.9% and 70%, respectively. Lower platelet count, autoimmune hepatitis (AIH) 2, and PELD/MELD score were found to be significant predictors of mortality on univariate analysis, which were not significant on multivariate modelling.Thecomplications, graft and patient survival rates in our experience were quite encouraging, and are comparable with the best centers worldwide. After instituting appropriate treatment, early referral of such patients to an equipped center should be facilitated.

Long-term Outcome of Transjugular Intrahepatic Portosystemic Shunt in Children With Portal Hypertension.

A proportion of children with chronic liver disease have severe portal hypertension (PH) and a preserved synthetic and biliary function. In our institution these children have been managed with transjugular intrahepatic portosystemic shunts (TIPS). We aimed to evaluate the long-term patency of TIPS placed in pediatric patients with PH. Retrospective study of children who underwent TIPS in the last 15 years. We compared patients with cirrhotic PH to those with noncirrhotic PH, and all with an historical cohort of children who underwent a surgical portosystemic shunt. Kaplan-Meier analysis measured long-term shunt patency. Twenty-nine patients were recorded (cirrhotic PH = 11, noncirrhotic PH = 18, mean age 10.3 years[±4.3], mean weight 36.7 kg [±20.1], mean pediatric end-stage liver disease score 4.1 [±7.1]); in 5 TIPS was placed after split liver transplantation. Indication for TIPS was variceal bleeding in 18, refractory ascites in 11. Primary patency rates at 6 months and at 1, 2, and 4 years were 91%, 83%, 60%, and 46%, respectively. At last follow-up (mean of 2.8 years [±2.4, range 0.1-8.1 years]) secondary patency (after radiological revision) was 100%. The patency rate of the historical cohort of patients who underwent a surgical portosystemic shunt was 26 of 31 (82%) at a median follow-up of 12.5 years (1.6-25.8). TIPS appears to have a high mid-term patency rate, especially if monitored and revised. Its high clinical success rate, along with a minimally invasive approach, suggests that in this setting TIPS should not be regarded only as a bridge to liver transplantation.

Evaluation of Underlying Liver Disease and Its Severity in Children Referred for Liver Transplant: a Single-Center Report From Nemazee Hospital of Shiraz.

Liver transplant has been used as a curative approach for children with end-stage liver diseases. Here, we describe the underlying causes for pediatric liver transplant performed at the Shiraz Organ Transplantation Center, Nemazee Hospital, Shiraz, Iran. In this cross-sectional descriptive study, children < 18 years old who were candidates for liver transplant from 2007 to 2010 at the Shiraz Organ Transplantation Center were included. Patients were evaluated for their underlying diseases leading to liver failure. Disease severity was assessed and compared with Pediatric End-Stage Liver Disease model and the Model for End-Stage Liver Disease scores. Of 107 patients, 60.8% were males and 39.2% were females. The mean age was 11.6 ± 4.9 years. Thirteen patients (12.5%) were < 2 years old, 26 (24%) were 2 to 6 years old, 33 (30.8%) were 6 to 12 years old, and 35 (32.7%) were 12 to 18 years old. Underlying liver diseases comprised biliary atresia (27.1%), cryptogenic cirrhosis (21.5%), autoimmune cirrhosis (13.1%), familial intrahepatic cholestasis (11.2%), Wilson disease (9.3%), tyrosinemia (7.4%), neonatal hepatitis (4.7%), congenital hepatic fibrosis (3.7%), and Caroli disease (1.9%). Jaundice (83.2%), ascites (57%), and esophageal varices (43%) were the most common clinical findings. Mean serum direct bilirubin, total bilirubin, international normalized ratio, and serum creatinine values were 3.6 ± 0.8 mg/dL, 9.3 ± 9.1 mg/dL, 2.1 ± 1.1, and 0.6 ± 0.2 mg/dL, respectively. The mean Pediatric End-Stage Liver Disease score in children < 12 years old was 11.4 ± 9.1. The mean Model for EndStage Liver Disease score in children > 12 years old was 13.7 ± 5.9. There were no differences in scores among sex, age groups, or different etiologies. Scores for disease severity were not significantly different with regard to different causes of underlying diseases for liver transplant in Iranian children.

Acute Liver Failure: Outcome and Value of Pediatric End-Stage Liver Disease Score in Pediatric Cases.

The aims of this study were to analyze the characteristics of patients with acute liver failure (ALF) in our center and evaluate the prognostic value of the Pediatric End-Stage Liver Disease (PELD) score calculated at admission. A retrospective analysis of patients with ALF younger than 15 years between 2005 and 2013 was performed. Information collected included age, sex, etiology of ALF, laboratory tests, PELD score, stage of encephalopathy, and need for liver support devices such as MARS and/or liver transplant (LT) and survival. A poor prognosis was defined as the need for LT or death. Twenty patients (10 male patients, 50%) with a median age of 2.6 years (3 days-14.5 y old) were included. Acute liver failure was of indeterminate cause in 5 cases (25%). Within the recognized causes, the most frequent were viral hepatitis (herpes simplex virus, adenovirus, influenza B, Epstein-Barr virus), autoimmune hepatitis, and metabolopathies. Sixty percent presented with encephalopathy at diagnosis. Four patients were aided by a MARS liver support device. Six patients received a total of 7 transplants, all from deceased donors. The rate of spontaneous recovery was 45%. Currently 13 patients (65%) are living, 4 of them with an LT. Six patients died because of ALF. The mean PELD score of patients with spontaneous recovery was 15.31 (5.3-27.6) compared with a mean of 29.5 (17.2-39.4) in LT patients and 31.55 (15.8-52.4) for nonsurvivors (P = 0.013). High PELD scores at diagnosis were accurate predictors of a poor prognosis in our patients with ALF. This model may help in the clinical management of this entity, although prospective validation is needed.

Long Term Outcomes of Pediatric Liver Transplantation According to Age

Liver transplantation (LT) has been the key therapy for end stage liver diseases. However, LT in infancy is still understudied. From 1992 to 2010, 152 children had undergone LT in Seoul National University Hospital. Operations were performed on 43 patients aged less than 12 months (Group A) and 109 patients aged over 12 months (Group B). The mean age of the recipients was 7 months in Group A and 74 months in Group B. The patients' survival rates and post-LT complications were analyzed. The mean Pediatric End-stage Liver Disease score was higher in Group A (21.8) than in Group B (13.4) (P = 0.049). Fulminant hepatitis was less common in Group A (4.8%) than in Group B (13.8%) (P = 0.021). The post-transplant lymphoproliferative disorder and portal vein complication were more common in Group A (14.0%, 18.6%) than in Group B (1.8%, 3.7%) (P = 0.005). However, the 1, 5, and 10 yr patient survival rates were 93%, 93%, and 93%, in Group A and 92%, 90%, and 88% in Group B (P = 0.212). The survival outcome of pediatric LT is excellent and similar regardless of age. LTs in infancy are not riskier than those of children.

Pediatric End‐stage Liver Disease Score in Acute Liver Failure to Assess Poor Prognosis

Although establishing accurate prognosis in acute liver failure (ALF) is of paramount importance, prognostic scoring systems still fail to achieve success. The pediatric end-stage liver disease (PELD) score has been used as a predictor of mortality in children with chronic liver disease listed for liver transplantation (LT); however, experience with the PELD score in ALF is limited. The goal of the present study was to investigate the prognostic accuracy of the PELD score in children with ALF. PELD score was calculated based on results of blood tests obtained at hospital admission from June 1999 to January 2009, in 40 consecutive patients younger than 18 years who presented with ALF. Poor outcome was defined as LT or death. Mean (±SD) age of patients was 5.3 ± 4.4 years (range 6 months-17 years); 52.5% were girls (n = 21). Etiologies of ALF were hepatitis A in 42.5% (17), indeterminate in 35% (14), autoimmune hepatitis in 17.5% (type 1 12.5% [n5], type 2 5% [n2]), and toxic in 5% (2). Mean PELD score was 34.92 ± 10.48 (range 6-55). PELD scores obtained on admission were significantly higher among nonsurvivors (39.8 ± 9.5) and recipients of an LT (39 ± 7.1) compared with those who survived without LT (31.3 ± 3) (P < 0.001). A cutoff of 33 in PELD score using receiver operating characteristic curves showed 81% specificity and 86% sensitivity for poor outcome (positive predictive value 92% and negative predictive value 69%; area under curve 0.88 95% confidence interval 0.77-1.0; P < 0.0001). PELD score obtained upon admission may be of help to establish the optimal timing for LT evaluation and listing. Further validation in larger and more diverse populations is needed.

Living donor liver transplantation for acute liver failure in pediatric patients caused by the ingestion of fireworks containing yellow phosphorus

Yellow phosphorus is a protoplasmic toxicant that targets the liver. The ingestion of fireworks containing yellow phosphorus, either by children who accidentally consume them or by adults who are attempting suicide, often results in death due to acute liver failure (ALF). We present the outcomes of 10 children who ingested fireworks containing yellow phosphorus. There were 6 boys and 4 girls, and their ages ranged from 21 to 60 months. One patient remained stable without liver complications and was discharged. Three patients died of hepatorenal failure and cardiovascular collapse, and living donor liver transplantation (LDLT) was performed for 6 patients. The patients had grade II or III encephalopathy, a mean alanine aminotransferase level of 1148.2 IU/L, a mean aspartate aminotransferase level of 1437.5 IU/L, a mean total bilirubin level of 6.9 mg/dL, a mean international normalized ratio of 6.6, a mean Pediatric End-Stage Liver Disease score of 33.7, and a mean Child-Pugh score of 11.3. Postoperatively, 2 patients had persistent encephalopathy and died on the second or third postoperative day, and 1 patient died of cardiac arrest on the first postoperative day despite a well-functioning graft. The other 3 patients were still alive at a mean of 204 days. In conclusion, the ingestion of fireworks containing yellow phosphorus causes ALF with a high mortality rate. When signs of irreversible ALF are detected, emergency LDLT should be considered as a lifesaving procedure; however, if yellow phosphorus toxicity affects both the brain and the heart in addition to the liver, the mortality rate remains very high despite liver transplantation.

934 Artificial Liver Support in Children with Fulminant Hepatic Failure: Our Experience

Background: Fulminant hepatic failure (FHF) is characterized by the development of encephalopathy and impaired synthetic liver capacity in patients with previous normal liver function or well compensated liver disease. Orthotopic liver transplantation (OLTx) seems to be the only therapy proven to improve patient survival in most cases. The role of artificial liver support encompasses toxin removal and the reversal of the inflammatory process. Design: Retrospective analysis in children affected by FHF who underwent artificial liver support. Setting: Pediatric Intensive Care Unit in a Tertiary referral Hospital. Patients: 10 children with FHF were admitted to our PICU from January 1 2005 to December 31 2008. Results: Fifty per cent of patients were female and mean age was 57 months± 9,5. Most common cause of FHF was autoimmune (50%) followed by drugs and toxins induced (40%). The mean Pediatric End-Stage Liver Disease (PELD) score was 33± 9 and the electroencephalography recording showed severe signs of encephalopaty in all the patients. All patients but one underwent continuous veno-venous hemodiafiltration (CVVH). Delay from suspected diagnosis to the beginning of the depuration therapy ranged from few hours to 3 days. 5 patients underwent OLTx. All patients were dicharged with a good neurological status. Conclusions: The most important factor in predicting survival in FHF are the degree of encephalopathy, the patient's age, and the cause of FHF. Artificial support systems did not appear to affect the mortality rate and may “bridge” patients to OLTx or spontaneous recovery.

Atrial septal defect in end-stage liver disease children before and after liver transplantation

Atrial septal defect (ASD) is a common congenital heart defect. The course and impact of hemodynamically insignificant ASD in end-stage liver disease (ESLD) patients remains to be elucidated. Our objective is to present our experience in live donor liver transplantation in children with secundum type of ASD and to find out whether ASD has an impact on the outcome of liver transplantation. Fourteen recipients (7 male, 7 female) whose median age was 14.2 months (range, 8-28) were included. The diagnosis of secundum type of ASD was confirmed by transthoracic 2-dimensional Doppler echocardiography preoperatively. The mean Child's score was 9.9, and the mean Pediatric End-stage Liver Disease Score was 14.7. The ASD were classified based on physiologic-hemodynamic (insignificant vs significant) and structural size (small [</=4 mm], medium [5-9 mm], or large [>/=10 mm]) parameters. Only 1 patient showed hemodynamically significant ASD based on echocardiography and cardiac catheterization findings. Six small ASD spontaneously closed during the waiting period for transplantation. Four small ASD spontaneously closed posttransplant. The medium- and large-sized ASD persisted or increased in size posttransplantation. There were no perioperative cardiac complications. There were no neurologic complications. All patients are alive with the original grafts. The median follow-up was 49.7 months (range, 19.8-79.4). Hemodynamic insignificant ASD seems to not impact the outcome of liver transplantation in children with ESLD. Further, this series demonstrated that transplantation can be successfully and safely performed in the presence of hemodynamically stable patients with small- to large-sized ASD.

Comparison of Child-Turcotte-Pugh and Pediatric End-Stage Liver Disease Scoring Systems to Predict Morbidity and Mortality of Children Awaiting Liver Transplantation

Background The pediatric end-stage liver disease (PELD) scoring system has been used widely for prioritizing children awaiting orthotopic liver transplantation (OLT). The aim of the present study was to compare the Child-Turcotte-Pugh scoring system with PELD to predict morbidity and mortality of children scheduled for OLT before the organ was available. Materials and Methods From 1999 to 2006, 83 infants and children were evaluated and scheduled for OLT. Child and PELD scores were determined according to the initial assessment at the time of listing. Outcome was examined using records and follow-up data. Results Among 83 patients, 12% were Child A; 53%, Child B; and 35%, Child C. The mean PELD score at listing was 19.8 ± 12.8. Patients with Child scores A, B, and C displayed mean PELD scores of 7.1 ± 4.9, 15.7 ± 9.3, and 30.5 ± 11.7, respectively. Child classification and scoring showed a positive correlation with the PELD score (Spearman’s correlation coefficient: 0.666, P = .001). A higher PELD score was associated with greater morbidity and mortality. Conclusion Child classification has several shortcomings; therefore, PELD scores appear to be the best metric to prioritize children listed for OLT.

Cardiac Surgery in Children With End-Stage Liver Disease Awaiting Liver Transplantation

Cardiac repair for congenital heart disease in children awaiting liver transplantation presents unique therapeutic challenges and dilemmas. We tested the hypothesis that operations in these children requiring cardiopulmonary bypass (CPB) were not associated with prohibitive morbidity and mortality. Over the last 10 years (1994-2004), five infants were identified in our database with end-stage liver disease and awaiting liver transplantation that required cardiac surgery. Primary end point for the study was mortality. Secondary end points included morbidity and time to liver transplantation. The new pediatric end-stage liver disease (PELD) model was used to score liver disease severity. Three boys and two girls with mean age of 8.6 months (range, 1.5-21 months) and mean PELD of 18.0 (range, 10-29) required CPB for repair. The only early mortality in the series occurred after cardiac arrest during creation of a central shunt. The child expired two days later despite extracorporeal membrane oxygenation support. The patient had important myocardial hypertrophy. All other patients survived and underwent successful liver transplantation. Children with significant congenital heart disease awaiting liver transplantation can undergo safe cardiac repair with judicious perioperative support thereby reducing the risks of subsequent liver transplantation.

National and regional analysis of exceptions to the pediatric end-stage liver disease scoring system (2003-2004)

Since February 2002, the Pediatric End Stage Liver Disease (PELD) scoring system has been utilized as a means of prioritizing children for liver transplantation. The United Network for Organ Sharing database was queried to assess utilization of PELD in 2003 and 2004; 682 liver transplants were performed in pediatric recipients where the PELD score was potentially the primary determinant of liver allocation. In the majority of circumstances (53%) the actual calculated PELD score was not utilized to determine liver allocation. An exception to the PELD score was utilized in 24% of cases. An additional 29% of the children were listed as urgent (status 1) without having acute liver failure. There was considerable regional variability in the inability to utilize actual PELD scores for liver allocation to children. PELD utilization was higher in regions of the country where pediatric donor organs were more available, presumably because children have some priority for organs from pediatric donors. There were 87 deaths in children awaiting liver transplantation. The mean PELD score in children without acute liver failure or metabolic liver disease (n = 33) near the time of death was 24.2, which has a purported 3-month risk of mortality of less than 10%. In our opinion the assigned 3-month risk of mortality associated with PELD scores is understated. Three-month mortality risk is used to inter-convert the adult and pediatric scoring systems. Therefore exceptions to the scoring system are required when children compete with adults for donor organs. In conclusion, urgent reassessment of the PELD scoring system is needed to avoid morbidity and mortality in children.