Objectives-To determine short-term outcome for children with acute liver failure (ALF) as it relates to etiology, clinical status, patient demographics and to determine prognostic factors.Study design-A prospective, multi-center case study collecting demographic, clinical, laboratory and short-term outcome data on children from birth to 18 years with ALF. Patients without encephalopathy were included if the prothrombin time and INR remained ≥ 20 seconds and/or >2, respectively, despite vitamin K. Primary outcome measures three weeks after study entry were death, death after transplant, alive with native liver, alive with transplanted organ.Results-The etiology of ALF in 348 children included acute acetaminophen toxicity (14%), metabolic disease (10%), autoimmune liver disease (6%), non-APAP drug-related hepatotoxicity (5%), infections (6%), other diagnosed conditions (10%); 49% were indeterminate. Outcome varied between patient sub-groups; 20% with non-acetaminophen ALF died or underwent liver transplantation and never developed clinical encephalopathy.Conclusions-Etiologies of ALF in children differ from adults. Clinical encephalopathy may not be present in children. The high percentage of indeterminate cases provides an opportunity for investigation.Corresponding Address: Robert H. Squires, Jr., M.D., Professor of Pediatrics, University of Pittsburgh, Children's Hospital of Pittsburgh, 3705 Fifth Avenue, Pittsburgh, PA 15213, Phone: 412-692-8181, Fax: 412-692-7355, Email: Robert.squires@chp.edu. edited by WFB Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. (11), development of a reliable prognostic score will be useful in allocating organs to the most needy patients. NIH Public AccessThe Pediatric Acute Liver Failure (PALF) study group was formed in 1999 to develop a database that would facilitate an improved understanding of the etiopathogenesis, treatment and outcome of ALF in children. These data will also serve to identify factors that will help to predict the likelihood of death or need for liver transplant. Methods OrganizationThe PALF study group began as an adjunct to the Data CollectionFollowing informed consent from a parent or legal guardian, demographic, clinical and laboratory information were recorded daily for seven days. In most patients, an additional aliquot of serum or plasma was collected on each of the seven study days, frozen at −70° C and then shipped to the Data Coordinating Center (DCC) located at the University of Texas Southwestern Medical Center in Dallas, Texas. Diagnostic evaluation and medical management were consistent with the...

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N-acetylcysteine (NAC) was found to improve transplantation-free survival in only those adults with non-acetaminophen (non-APAP) acute liver failure (ALF) and grade 1–2 hepatic encephalopathy (HE). Because non-APAP ALF differs significantly between children and adults, the Pediatric Acute Liver Failure (PALF) Study Group evaluated NAC in non-APAP PALF. Children from birth through age 17 years with non-APAP ALF enrolled in the PALF registry were eligible to enter an adaptively allocated, doubly masked, placebo-controlled trial using a continuous intravenous infusion of NAC (150 mg/kg/day in 5% dextrose in water [D5W]) or placebo (D5W) for up to 7 days. The primary outcome was 1-year survival. Secondary outcomes included liver transplantation-free survival, liver transplantation (LTx), length of ICU and hospital stays, organ system failure and maximum HE score. A total of 184 participants were enrolled in the trial with 92 in each arm. The 1-year survival did not differ significantly (p=0.19) between the NAC (73%) and placebo (82%) treatment groups. The 1-year LTx-free survival was significantly lower (p=0.03) in those who received NAC (35%) than those who received placebo (53%), particularly, but not significantly so, among those less than 2 years old with HE grade 0–1 (NAC 25%; placebo 60%; p=0.0493). There were no significant differences between treatment arms for hospital or ICU length of stay, organ systems failing, or highest recorded grade of HE. Conclusion NAC did not improve 1-year survival in non-APAP PALF. 1-year LTx-free survival was significantly lower with NAC, particularly among those < 2 years old. These results do not support broad use of NAC in non-APAP PALF and emphasizes the importance of conducting controlled pediatric drug trials, regardless of results in adults.

In a multinational study of children with acute liver failure, we found that incorporating diagnostic test recommendations into electronic medical record order sets accessed at time of admission reduced the percentage with an indeterminate diagnosis that may have reduced liver transplants without increasing mortality. Widespread use of this approach could significantly enhance care of acute liver failure in children.

A small but significant percentage of children with acute liver failure of indeterminate cause tested positive for acetaminophen cysteine protein adducts, strongly suggesting acetaminophen toxicity as the cause of acute liver failure. An assay for the detection of acetaminophen cysteine protein adducts can aid the diagnosis of acetaminophen-related liver injury in children.

Background: The COVID-19 pandemic has drastically changed healthcare systems and training around the world. The Training Committee of the North American Society for Pediatric Gastroenterology, Hepatology and Nutrition (NASPGHAN) sought to understand how COVID-19 has affected pediatric gastroenterology fellowship training. Methods: A 21 question survey was distributed to all 77 pediatric gastroenterology fellowship program directors (PDs) in the NASPGHAN program director database via email on April 7.

The optimal management strategy for children with immune‐tolerant chronic hepatitis B virus (HBV) infection remains unknown. The purpose of this clinical trial was to determine the safety and efficacy of therapy with entecavir and peginterferon in a group of children in the immune‐tolerant phase of HBV infection. Children with immune‐tolerant features of chronic hepatitis B (CHB) received entecavir once‐daily in a dose of 0.015 mg/kg (0.5 mg maximum) for 48 weeks; peginterferon alfa‐2a (180 µg/1.73m2 subcutaneously) once‐weekly was added at the end of week 8 and continued until week 48. The primary endpoint was lack of detectable hepatitis B e antigen (HBeAg) with HBV DNA levels ≤1,000 IU/mL 48 weeks after stopping therapy. Sixty children (75% female), median age 10.9 (range, 3.4‐17.9) years, were enrolled. All were positive for hepatitis B surface antigen (HBsAg) and HBeAg and had high levels of HBV DNA with normal or minimally elevated levels of alanine aminotransferase (ALT). Fifty‐five children completed the entire 48‐week course of therapy. At 48 weeks after treatment ended (week 96), 2 children (3%) achieved the primary endpoint and were also HBsAg negative and anti–hepatitis B surface antigen antibody (anti‐HBs) positive. One child was HBeAg positive but HBsAg negative at week 60; another was HBeAg negative but HBsAg positive at week 72, which were their last clinic visits. In the remaining children, serum ALT and HBV DNA levels at week 96 were similar to baseline. Thirty‐seven children experienced adverse events (AEs), and 1 had a serious AE (SAE). Conclusion: The combination of entecavir and peginterferon for up to 48 weeks rarely led to loss of HBeAg with sustained suppression of HBV DNA levels in children in the immune‐tolerant phase of HBV infection, and treatment was associated with frequent AEs.

Rotavirus and astrovirus are common symptomatic infections on pediatric wards and contribute greatly to inpatient morbidity. Adenoviruses played a limited role in gastroenteritis in hospitalized children in this study.