Finance, race, ethnicity, and spoken language impact clinical outcomes for children with acute liver failure.

BACKGROUND: Pediatric acute liver failure (PALF) is an emergency, necessitating prompt referral and management at an experienced liver transplant center. Social determinants of health (SDOH) drive healthcare disparities and can affect many aspects of disease presentation, access to care, and ultimately clinical outcomes. Potential associations between SDOH and PALF outcomes, including spontaneous recovery (SR), liver transplant (LT) or death, are unknown. This study aims to investigate how SDOH may affect PALF and therefore identify areas for intervention to mitigate unrecognized disparities. METHODS: A retrospective, single-center cohort was analyzed and then compared and validated with data from the multicenter National Institutes of Health PALF Study Group. The single-center review included 145 patients admitted with PALF using diagnostic codes. Medical records were reviewed to extract patient demographics, family structure, inpatient social worker assessments, and clinical outcomes. Data were stratified by outcome. RESULTS: This analysis determined that level of family support (p = .02), caretaker employment (p = .02), patient age, race, and language (p = .01) may impact clinical outcomes. Specifically, the cohort of children that died had the largest proportion of non-English speaking patients with limited support systems and parents who worked full-time. Conversely, patients who underwent LT more often belonged to English-speaking families with a homemaker and extensive support systems. CONCLUSION: This study suggests that SDOH impact PALF outcomes and highlights patient populations facing additional challenges during an already complex healthcare emergency. These associations may indicate unconscious biases held by transplant teams when evaluating waitlist candidacy, as well as barriers to healthcare access. Strategies to better understand the broader applicability of our findings and, if confirmed, efforts to mitigate social disparities, may improve clinical outcomes in PALF.

CHALF Score: A Novel Tool to Rapidly Risk Stratify Children in Need of Liver Transplant Evaluation During Acute Liver Failure.

BACKGROUND: Pediatric acute liver failure (PALF) can require emergent liver transplantation (LT, >25%) or lead to death (~15%). Existing models cannot predict clinical trajectory or survival with native liver (SNL). We aimed to create a predictive model for PALF clinical outcomes based on admission variables. METHODS: A retrospective, single-center PALF cohort (April 2003 to January 2022) was identified using International Classification of Disease codes, selected using National Institutes of Health PALF Study Group (PALFSG) criteria, and grouped by clinical outcome (SNL, LT, or death). Significant admission variables were advanced for feature selection using least absolute shrinkage and selection operator regression with bootstrapping (5000×). A predictive model of SNL versus LT or death was created using logistic regression and validated using PALFSG data. RESULTS: Our single-center cohort included 147 patients (58% SNL, 32% LT, 10% expired), while the PALFSG validation cohort included 492 patients (50% SNL, 35% LT, 15% expired). Admission variables associated with SNL included albumin (odds ratio [OR], 16; P < 0.01), ammonia (OR, 2.37; P < 0.01), and total bilirubin (OR, 2.25; P < 0.001). A model using these variables predicted SNL versus LT or death with high accuracy (accuracy [0.75 training, 0.70 validation], area under the curve [0.83 training, 0.78 validation]). A scaled score (CHLA-acute liver failure score) was created that predicted SNL versus LT or death with greater accuracy (C statistic 0.83) than Pediatric End-Stage Liver Disease (C statistic 0.76) and admission liver injury unit (C statistic 0.76) scores. CONCLUSIONS: The CHLA-acute liver failure score predicts SNL versus LT or mortality in PALF using admission laboratories with high accuracy. This novel, externally validated model offers an objective guide for urgent referral to a pediatric LT center.

Hepatic Encephalopathy in Children.

Hepatic encephalopathy, characterized by mental status changes and neuropsychiatric impairment, is associated with chronic liver disease as well as acute liver failure. In children, its clinical manifestations can be challenging to pinpoint. However, careful assessment for the development of hepatic encephalopathy is imperative when caring for these patients as progression of symptoms can indicate impending cerebral edema and systemic deterioration. Hepatic encephalopathy can present with hyperammonemia, but it is important to note that the degree of hyperammonemia is not indicative of severity of clinical manifestations. Newer forms of assessment are undergoing further research, and include imaging, EEG and neurobiomarkers. Mainstay of treatment currently includes management of underlying cause of liver disease, as well as reduction of hyperammonemia with either enteral medications such as lactulose and rifaximin, or even with extracorporeal liver support modalities.

Interoceptive hunger, eating attitudes and beliefs.

Interoceptive individual differences have garnered interest because of their relationship with mental health. One type of individual difference that has received little attention is variability in the sensation/s that are understood to mean a particular interoceptive state, something that may be especially relevant for hunger. We examined if interoceptive hunger is multidimensional and idiosyncratic, if it is reliable, and if it is linked to dysfunctional eating and beliefs about the causes of hunger. Participants completed a survey just before a main meal, with most retested around 1 month later. We found that interoceptive hunger has 11 dimensions, and while people differ considerably in their combinations of interoceptive hungers, these represent only 4% of all possible permutations. Hunger reports were reliable. We found relationships between variability in hunger interoception and dysfunctional eating, especially for uncontrolled eating. We also found that hunger beliefs were in some cases strongly related to aspects of hunger interoception. The implications of these findings are discussed.

The development of interoceptive hunger signals.

Hunger is often reported when people experience certain internal sensations (e.g., fatigue) or when they anticipate that a food will be good to eat. The latter results from associative learning, while the former was thought to signal an energy deficit. However, energy-deficit models of hunger are not well supported, so if interoceptive hungers are not "fuel gauges," what are they? We examined an alternate perspective, where internal states signaling hunger, which are quite diverse, are learned during childhood. A basic prediction from this idea is offspring-caregiver similarity, which should be evident if caregivers teach their child the meaning of internal hunger cues. We tested 111 university student offspring-primary caregiver pairs, by having them complete a survey about their internal hunger states, alongside other information that may moderate this relationship (i.e., gender, body mass index, eating attitudes, and beliefs about hunger). We observed substantial similarity between offspring-caregiver pairs (Cohen's ds from 0.33 to 1.55), with the main moderator being beliefs about an energy-needs model of hunger, which tended to increase similarity. We discuss whether these findings may also reflect heritable influences, the form that any learning might take, and the implications for child feeding practices.

Revisiting transplant immunology through the lens of single-cell technologies.

Solid organ transplantation (SOT) is the standard of care for end-stage organ disease. The most frequent complication of SOT involves allograft rejection, which may occur via T cell- and/or antibody-mediated mechanisms. Diagnosis of rejection in the clinical setting requires an invasive biopsy as there are currently no reliable biomarkers to detect rejection episodes. Likewise, it is virtually impossible to identify patients who exhibit operational tolerance and may be candidates for reduced or complete withdrawal of immunosuppression. Emerging single-cell technologies, including cytometry by time-of-flight (CyTOF), imaging mass cytometry, and single-cell RNA sequencing, represent a new opportunity for deep characterization of pathogenic immune populations involved in both allograft rejection and tolerance in clinical samples. These techniques enable examination of both individual cellular phenotypes and cell-to-cell interactions, ultimately providing new insights into the complex pathophysiology of allograft rejection. However, working with these large, highly dimensional datasets requires expertise in advanced data processing and analysis using computational biology techniques. Machine learning algorithms represent an optimal strategy to analyze and create predictive models using these complex datasets and will likely be essential for future clinical application of patient level results based on single-cell data. Herein, we review the existing literature on single-cell techniques in the context of SOT.

Pediatric acute liver failure: Reexamining key clinical features, current management, and research prospects.

This review aims to synthesize the most updated research, outcomes, and trends in the field of pediatric liver transplantation (LT), specifically focusing on children who have suffered from acute liver failure. Pediatric acute liver failure is a dynamic, life-threatening condition that can either self-resolve or lead to death. LT is a lifesaving intervention. With the introduction of technical variant grafts and recent immunosuppression modifications, overall patient survival, graft survival, and waitlist mortality have improved. Furthermore, recent advances in the knowledge of immunologic mediators of acute liver failure offer the possibility of more detailed understanding of the pathophysiology and new areas for research. Given the success of living donor LT for pediatric patients with acute liver failure, this option should continue to be actively considered as an alternative treatment option for patients who are listed for transplantation and are managed at a multidisciplinary tertiary care transplant center.

Approach to Pediatric Obesity and Nonalcoholic Fatty Liver Disease.

With the rapidly increasing numbers of children diagnosed with obesity, pediatricians are facing more and more challenges regarding the complex care of these patients. Pediatric nonalcoholic fatty liver disease (NAFLD) is now the most prevalent cause of pediatric chronic liver disease, given its association with obesity. As NAFLD increases a child's risk of developing long-term complications including cirrhosis and hepatocellular carcinoma, efficient diagnosis and effective management is paramount. This article aims to provide a brief overview of NALFD, and discuss the updated diagnosis and management approach for pediatric NAFLD, with a particular focus on the role of the pediatrician. [Pediatr Ann. 2021;50(11):e474-e477.].

Liver Biopsy in Children.

Liver biopsy is the cornerstone of medical decision-making for a wide range of hepatic diseases in children. The indications for liver biopsy vary greatly depending on the ease of diagnosis with non-invasive tests, the need to stage of disease, and the role of histological evaluation in management of liver disease. Multiple methods of liver biopsy are available to the clinician and are utilized based on clinical circumstances, cost, and consideration of contraindications. Collaboration between the clinician and pathologist is important in order to handle the tissue sample appropriately and interpret the histology. The purpose of this paper is to provide a broad overview of liver biopsy indications, techniques, pre- and post-biopsy care and complications, interpretations, contraindications, recent advancements, and pitfalls that occur with liver biopsies.