Pediatric Acute Liver Failure Secondary to Autoimmune Hepatitis in an Infant With Thrombocytopenia-Absent Radius (TAR) Syndrome: A Case Report.

Thrombocytopenia absent radius (TAR) syndrome is a rare genetic disorder that has been associated with food protein-induced allergic proctocolitis and transient leukemoid reactions, among other manifestations. There has been no prior reports of its association with autoimmune disease, more specifically, autoimmune hepatitis (AIH) or the development of pediatric acute liver failure (PALF). We present a case of an 8-month-old infant with TAR syndrome who presented with PALF, secondary to AIH with elevated liver-kidney microsomal antibody (>1:2560). She received a liver transplant and had a very complicated postoperative course including severe T-cell-mediated rejection, infection, biliary stricture, persistently elevated liver-kidney microsomal antibodies, and antibody-mediated rejection. Ultimately, these complications led to graft failure, severe sepsis, and death. This case highlights a new association of TAR syndrome with AIH and PALF and a potentially aggressive nature of AIH both pre- and post-transplant.

Nutritional management of children with acute kidney injury-clinical practice recommendations from the Pediatric Renal Nutrition Taskforce.

The nutritional management of children with acute kidney injury (AKI) is complex. The dynamic nature of AKI necessitates frequent nutritional assessments and adjustments in management. Dietitians providing medical nutrition therapies to this patient population must consider the interaction of medical treatments and AKI status to effectively support both the nutrition status of patients with AKI as well as limit adverse metabolic derangements associated with inappropriately prescribed nutrition support. The Pediatric Renal Nutrition Taskforce (PRNT), an international team of pediatric renal dietitians and pediatric nephrologists, has developed clinical practice recommendations (CPR) for the nutritional management of children with AKI. We address the need for intensive collaboration between dietitians and physicians so that nutritional management is optimized in line with AKI medical treatments. We focus on key challenges faced by dietitians regarding nutrition assessment. Furthermore, we address how nutrition support should be provided to children with AKI while taking into account the effect of various medical treatment modalities of AKI on nutritional needs. Given the poor quality of evidence available, a Delphi survey was conducted to seek consensus from international experts. Statements with a low grade or those that are opinion-based must be carefully considered and adapted to individual patient needs, based on the clinical judgment of the treating physician and dietitian. Research recommendations are provided. CPRs will be regularly audited and updated by the PRNT.

Acute liver failure and unique challenges of pediatric liver transplantation amidst a worldwide cluster of adenovirus-associated hepatitis.

Investigation into a recent cluster of acute hepatitis in children from the southeastern United States identified human adenovirus (HAdV) DNAemia in all 9 cases. Molecular genotyping in 5 of 9 (56%) children identified HAdV type 41 in all cases (100%). Importantly, 2 children from this cluster progressed rapidly to pediatric acute liver failure (PALF) and required liver transplantation. HAdV type 41, a known cause of self-limited gastroenteritis, has not previously been associated with severe cholestatic hepatitis and liver failure in healthy children. Adenovirus polymerase chain reaction assay and sequencing of amplicons performed on DNA extracted from formalin-fixed, paraffin-embedded liver tissue also identified adenovirus species F (HAdV type 40 or 41) in these 2 children with PALF. Transplant considerations and successful liver transplantation in such situations remain scarce. In this report, we describe the clinical course, laboratory results, liver pathology, and treatment of 2 children with PALF associated with HAdV type 41, one of whom developed secondary hemophagocytic lymphohistiocytosis. Their successful posttransplant outcomes demonstrate the importance of early multidisciplinary medical management and the feasibility of liver transplantation in some children with PALF and HAdV DNAemia.

A phase 2 trial of N-Acetylcysteine in Biliary atresia after Kasai portoenterostomy.

BACKGROUND: Biliary atresia (BA) is a life-threatening liver disease of infancy, characterized by extrahepatic biliary obstruction, bile retention, and progressive liver injury. The Kasai portoenterostomy (KP) is BA's only nontransplant treatment. Its success is variable and depends on restoration of hepatic bile flow. Many adjunctive therapeutics have been studied to improve outcomes after the KP, but none demonstrate effectiveness. This study tests if N-acetylcysteine (NAC), a precursor to the choleretic glutathione, improves bile flow after KP. METHODS: This report describes the design of an open-label, single center, Phase 2 study to determine the effect of NAC following KP on markers of bile flow and outcomes in BA. The intervention is intravenous NAC (150 mg/kg/day) administered continuously for seven days starting 0-24 h after KP. The primary outcome is normalization of total serum bile acid (TSBA) concentrations within 24 weeks of KP. The secondary objectives are to describe NAC therapy's effect on other clinical parameters followed in BA for 24 months and to report adverse events occurring with therapy. This study follows the "minimax" clinical trial design. DISCUSSION: This is the first clinical trial to test NAC's effectiveness in improving bile flow after KP in BA. It introduces three important concepts for future BA therapeutic trials: (1) the "minimax" study design, a pertinent design for rare diseases because it detects potential effects quickly with small subject size; (2) the more sensitive bile flow marker, TSBAs, which may correlate with positive long-term outcomes better than traditional bile flow markers such as serum bilirubin; and (3) liver enzyme changes immediately after KP, which can be a guideline for potential drug-induced liver injury in other BA peri-operative adjunctive therapeutic trials.