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Objectives: The Hepatology Committee of the European Society for Pediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) aims to educate pediatric gastroenterologists, members of ESPGHAN and professionals from other specialties promoting an exchange of clinical expertise in the field of pediatric hepatology., Methods: The 2020 single topic ESPGHAN monothematic 3-day conference on pediatric liver disease, was organized in Athens, Greece and was entitled " Acute Liver Failure" (ALF). ALF is a devastating disease with high mortality and in a considerable fraction of patients, the cause remains unresolved. As knowledge in diagnosis and treatment of ALF in infants and children has increased in the past decades, the objective was to update physicians in the field with developments in medical therapy and indications for liver transplantation (LT) and to identify areas for future research in clinical and neurocognitive outcomes in ALF., Results: We recently reported the epidemiology, diagnosis, and initial intensive care management issues in separate manuscript. Herewith we report on the medical treatment, clinical lessons arising from pediatric studies, nutritional and renal replacement therapy (RRT), indications and contraindications for LT, neurocognitive outcomes, new techniques used as bridging to LT, and areas for future research. Oral presentations by experts in various fields are summarized highlighting key learning points., Conclusions: The current report summarizes the current insights in medical treatment of pediatric ALF and the directions for future research., Competing Interests: The authors report no conflicts of interest., (Copyright © 2021 by European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition.)

Objectives: The Hepatology Committee of the European Society for Pediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) aims to educate pediatric gastroenterologists, members of ESPGHAN and professionals from other specialties promoting an exchange of clinical expertise in the field of pediatric hepatology. Herewith we have concentrated on detailing the recent advances in acute liver failure in infants and children., Methods: The 2020 ESPGHAN monothematic three-day conference on pediatric hepatology disease, entitled "acute liver failure" (ALF), was organized in Athens, Greece. ALF is a devastating disease with high mortality and most cases remain undiagnosed. As knowledge in diagnosis and treatment of ALF in infants and children has increased in the past decades, the objective was to update physicians in the field with the latest research and developments in early recognition, curative therapies and intensive care management, imaging techniques and treatment paradigms in these age groups., Results: In the first session, the definition, epidemiology, various causes of ALF, in neonates and older children and recurrent ALF (RALF) were discussed. The second session was dedicated to new aspects of ALF management including hepatic encephalopathy (HE), coagulopathy, intensive care interventions, acute on chronic liver failure, and the role of imaging in treatment and prognosis. Oral presentations by experts in various fields are summarized highlighting key learning points., Conclusions: The current report summarizes the major learning points from this meeting. It also identifies areas where there is gap of knowledge, thereby identifying the research agenda for the near future., Competing Interests: The authors report no conflicts of interest., (Copyright © 2021 by European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition.)

Objectives: The aim of the study was to describe the 5-year follow-up of children who received peginterferon and ribavirin in a global, open-label study., Methods: A 5-year follow-up study of 107 children and adolescents ages 3 to 17 years with chronic hepatitis C virus infection who received peginterferon and ribavirin for 24 or 48 weeks. No drugs were administered during follow-up., Results: Ninety-four patients were enrolled in the long-term follow-up portion of the study; the median duration of follow-up was 287 weeks (range, 73-339). Of 63 patients with sustained virologic response who were enrolled, 54 completed 5 years of follow-up; none had relapse in the 5-year follow-up period. Significant decreases in height z scores were observed during treatment. The effect of treatment on height z score was larger in patients treated for 48 weeks compared with those treated for 24 weeks (mean change from baseline to the end of treatment was -0.13 [P < 0.001] and -0.44 [P < 0.001] in the 24- and 48-week treatment groups, respectively). Among patients treated for 24 weeks, full recovery of height z scores to baseline was observed by 1 year of follow-up, whereas only partial recovery was observed during 5 years of follow-up in patients treated for 48 weeks (mean change from baseline to the final follow-up visit was -0.16 (P = NS) and -0.32 (P < 0.05) in the 24- and 48-week treatment groups, respectively). Similar patterns were observed for weight and body mass index z scores., Conclusions: Impairment of growth should be considered when assessing the risk-benefit profile of peginterferon/ribavirin therapy in children with hepatitis C virus infection. In deciding to treat children with chronic hepatitis C virus, considerations should include both deferring treatment in patients during optimal growth periods, and the possibility that interferon-free regimens may be available to children in the next 5 to 10 years.

Objectives: Survivors of pediatric liver transplantation are at risk for developing complications related to posttransplant immunosuppressive medications. Withdrawal is possible in selected patients but carries the risk of graft rejection and loss. We modeled the effect of withdrawing immunosuppressive medications on survival, cost, and quality-adjusted life-years (QALYs) in a hypothetical cohort of pediatric patients who received transplantation for biliary atresia with stable liver enzymes and no recent episodes of rejection, and who were free from immunosuppression-related adverse effects., Methods: A decision analysis tree was developed, and Monte Carlo simulations were used to track patients through the model during a 10-year time course with 1-year cycles. Data from the literature were used to assign probabilities to major clinical events and preference-based utility scores to the values of health outcomes. One-way and probabilistic sensitivity analyses were used to evaluate the impact of uncertainty., Results: Patients following the withdrawal strategy had a 10-year survival rate of 95.8% and experienced 8.61 QALYs versus 88.6% survival and 8.01 QALYs for those taking immunosuppressive medications. Each additional QALY is attained at a cost of -$18,992.41 and was therefore cost saving., Conclusions: Patients in our model who had their immunosuppression withdrawn had improved survival and QALYs with lower costs. Although every effort was made to validate the model, it is limited by the accuracy of the underlying assumptions. Therefore, clinical trials are needed to determine predictors of successful immunosuppression withdrawal to allow for personalization of medication regimens.

Objectives: There are limited data on the incidence of seizures and utility of brain imaging and electroencephalogram (EEG) to predict outcome of children with acute liver failure (ALF). We investigated the association between hepatic encephalopathy (HE) scores, abnormal EEG or neuroimaging, and short-term outcome., Methods: Single-center retrospective observational study of infants and children with ALF who underwent continuous EEG monitoring and brain imaging within 24 hours of admission to the intensive care unit (ICU)., Results: A total of 19 patients with ALF with a mean age of 6.8 ± 1.5 years were evaluated. The majority of cases (74%) were indeterminate. Of the total, 10 patients (53%) survived to discharge without liver transplant (LT), 5 (26%) received LT, and 4 (21%) died without LT. Seizures occurred in only 2 cases (19%). Patients who had an abnormal EEG on admission (n = 7) were significantly more likely to die or require LT (P < 0.05, Fisher exact test). Patients with either an admission HE score ≤ 2, or liver injury unit score <222, combined with a normal or mildly abnormal EEG were more likely to survive without LT. Neuroimaging was normal in the majority of cases (87%) and was not associated with outcome., Conclusions: Children with a moderate or severe abnormality of EEG background on admission were significantly more likely to require LT or to die. Children with an HE score ≤ 2, and a normal or only mildly abnormal EEG, were significantly more likely to survive without needing LT. These findings are an initial step toward distinguishing patients with ALF who may recover spontaneously from those who will require LT.

Objectives: To evaluate the safety, outcomes, and complications of percutaneous liver biopsies (PLB) in infants aged 0 to 3 months., Methods: We retrospectively reviewed the hospital records of all infants less than 3 months old who underwent PLB at Children's Memorial Hospital between July 1, 1997 and June 30, 2004 for complications surrounding the procedure and risk factors that might lead to complications., Results: Sixty-six PLBs were performed in 63 infants. Most patients tolerated the procedure without complications. Twelve complications were recorded, for an overall complication rate of 18%. Of these, five were directly related to the procedure, and seven were sedation related. Three patients experienced a drop in hemoglobin greater than 2 gm/dL, one patient developed a bile leak, and one developed a skin hematoma. Seven patients had respiratory difficulty related to sedation, which manifested as increased work of breathing or decreased respiratory rate with depression in pulse oximetry., Conclusion: We conclude that PLB in young infants is associated with a somewhat higher risk of complications than in older children, particularly complications related to sedation.

Background: The development of de novo autoimmune hepatitis as a long-term complication after liver transplantation has been recently reported. The authors describe five liver allograft recipients who developed chronic hepatitis associated with autoimmune features., Methods: Five of 155 liver transplant recipients at risk (2.5%) developed this particular form of graft dysfunction. The authors review the clinical records, liver histology, therapy, and outcome of these five patients., Results: Patients included two boys and three girls. Median age at transplantation was 3.5 years (range, 0.5-14 years), median age at presentation was 9 years (range, 2-17 years), and median interval after transplantation was 5.1 years (range, 1.5-9 years). Indications for liver transplant included biliary atresia in four patients and primary sclerosing cholangitis in one patient. At the time of presentation, all patients were receiving cyclosporine as their primary immunosuppressive agent. Only one patient had a history of rejection, which had resolved. All patients presented with increased transaminase levels, and one had a mildly elevated conjugated bilirubin level. Only one patient had constitutional complaints. Acute and chronic rejection, viral hepatitis, vascular insufficiency, and biliary tract obstruction were excluded. Antinuclear antibody levels were elevated in four patients (titer range, 1:160-1:640), one of whom also had positive antismooth muscle antibody (titer 1:80) results. The fifth patient had an elevated serum total protein level. Histologic analysis of liver biopsy samples from the five patients showed findings consistent with chronic autoimmune hepatitis. All patients were treated with standard therapy for autoimmune hepatitis, which included daily steroids and azathioprine. Cyclosporine doses were reduced in three patients and eliminated in two. All patients responded with normalization (n = 2) or improvement (n = 3) of liver transaminases within the first 3 months of therapy. Histologic analysis of the 3-month follow-up liver biopsy was normal (n = 2) or showed improvement in inflammation (n = 2). Two patients developed acute allograft rejection within 6 to 12 months after discontinuation or reduction in cyclosporine., Conclusions: Autoimmune hepatitis occurs after liver transplantation in patients without a previous history of autoimmune hepatitis. The risk of developing autoimmune hepatitis appears to be greater in children after liver transplantation than in the general pediatric population. Standard therapy for autoimmune hepatitis is effective.

The clinical findings in 33 patients with progressive familial intrahepatic cholestasis (PFIC) are presented. Symptoms developed almost invariably before 6 months of age with severe pruritus and moderate jaundice. Other clinical findings included wheezing and nosebleeds, fat-soluble vitamin deficiency states, and cholelithiasis. Lower values for gamma-glutamyl transpeptidase, averaging 15 IU/L before the administration of phenobarbital, and cholesterol, which averaged 156 mg/dl, are helpful in distinguishing PFIC from other pediatric cholestatic liver diseases. Autosomal recessive inheritance is probable. Twenty-six patients are alive at 12.9 +/- 6.7 years of age, all having had successful surgical treatment, either partial biliary diversion (n = 17) or orthotopic liver transplantation (n = 10). Seven patients died at a mean age of 3.9 +/- 2.4 years, as a result of liver failure in two, hepatocellular carcinoma in two, and complications of liver transplantation in three.

This work details the histologic findings in 84 liver biopsy specimens from 28 patients with progressive familial intrahepatic cholestasis (PFIC), who met the clinical criteria of early onset of chronic unremitting cholestasis, exclusion of any known metabolic or anatomic etiology, and low serum gamma-glutamyl transpeptidase (GGTP) values. Hepato-canalicular cholestasis and disruption of the liver cell plate arrangement were early, uniform findings, and giant cell transformation was found in 56% of initial biopsies. Duct loss was a prominent finding; 70% of patients had ductal paucity, and many had abnormal bile duct epithelium, suggesting degeneration. Fibrosis was seen in the samples from 16 patients, including bridging fibrosis in specimens obtained from six patients during the first 2 years of life. Proliferating ductules at the margins of portal tracts increased as fibrosis progressed and were especially prominent in end-stage histology. Cirrhosis developed in nine of these patients and had a characteristic histologic pattern, consisting of biliary cirrhosis with diffuse stellate lobular fibrosis associated with severe cholestasis and pseudoacinar transformation. Mallory hyalin and hepatocellular carcinoma were observed in materials from some patients with advanced cirrhosis. The constellation of histologic findings in PFIC forms a recognizable pattern, and the liver histology appears to have a predictable progression.

We reviewed data from 184 percutaneous liver biopsies performed as an outpatient procedure in 104 patients (5 weeks to 22 years of age) over a 4-year period. Hepatic allograft rejection was the indication for 130 of the biopsy procedures, while 54 were performed for a variety of indications in patients who had not undergone transplant. Abnormalities of coagulation that necessitated correction were present in 19 patients at the time of biopsy. Patients tolerated the procedure well. There were no major complications. None of the patients required blood product transfusion or hospitalization as a result of the procedure. Two patients suffered respiratory depression as a complication of sedation, which was easily reversed with administration of intravenous naloxone. Two specimens were insufficient for interpretation. We conclude that percutaneous liver biopsy in the proper outpatient setting can reduce the need for hospitalization solely for the purpose of the procedure.

We report the case of a 21-month-old child with a fibroinflammatory tumor of the liver causing biliary obstruction. The patient had fever, diarrhea, and jaundice. Abdominal ultrasonography, computerized tomography, and endoscopic retrograde cholangiopancreatography demonstrated the tumor to be in the porta hepatis. Growth of the mass resulted in destruction of the common hepatic duct, and chronic obstruction led to biliary cirrhosis over 4 months' time. Histologic study of the tumor revealed a fibrous stroma infiltrated by inflammatory cells. The patient was successfully treated with an orthotopic liver transplantation and is doing well 18 months following initial diagnosis without evidence of recurrence.