Xanthakos, Stavra A.

Pediatric metabolic dysfunction–associated steatotic liver disease (MASLD) has become more prevalent on a global scale over the last decades and is associated with significant comorbidities in childhood and a 40-fold higher risk of early mortality in young adulthood. MASLD has now become the leading indication for liver transplantation in young adults in the United States. However, pediatric MASLD is still perceived as an indolent condition by many patients, families, and clinicians. In this Call to Action, we aim to raise awareness of pediatric MASLD as a public health crisis. Herein, we describe insufficient screening and disease staging practices, and a lack of accurate non-invasive tests and effective pharmacotherapy, both stemming from a paucity of multicenter clinical trials in pediatric MASLD. We provide clear steps to address this public health emergency by promoting awareness campaigns, educating and empowering patients and families, addressing barriers including access to care, nutritional and exercise support programs, establishing multidisciplinary care, launching community initiatives, and conducting clinical trials in pediatric MASLD for an age-based evaluation of novel diagnostic and therapeutic options. We conclude by highlighting the urgent need for comprehensive public health policies to control the tide of pediatric MASLD and call upon stakeholders to act now.

AbstractAs rates of obesity rise worldwide, incidence of metabolic dysfunction‐associated steatotic liver disease (MASLD), formerly referred to as nonalcoholic fatty liver disease, is increasing, worsening the burden of healthcare systems. The council of the Federation of International Societies for Pediatric Gastroenterology, Hepatology, and Nutrition (FISPGHAN) identified the topic of MASLD epidemiology, treatment, and prevention as a global priority issue to be addressed by an expert team, with the goal to describe feasible and evidence‐based actions that may contribute to reducing MASLD risk. The FISPGHAN member societies nominated experts in the field. The FISPGHAN council selected and appointed members of the expert team and a chair. The subtopics included in this manuscript were chosen through a consensus of the experts involved. We review the epidemiology, natural history, and screening and management. We further expand to relevant public health measures aimed at MASLD prevention, including identifying interventions that could reduce risk factors (environmental and iatrogenic), optimize maternal and newborn health, and support healthier lifestyles for older children and adolescents on a local, national, and international scale. While recognizing that various aspects of population health and public policy can shape MASLD risk, we also review what we can do on an individual level to support our patients to reduce the significant burden of this ever rising disease in pediatrics.

The principal limitations of the terms NAFLD and NASH are the reliance on exclusionary confounder terms and the use of potentially stigmatising language. This study set out to determine if content experts and patient advocates were in favor of a change in nomenclature and/or definition. A modified Delphi process was led by three large pan-national liver associations. The consensus was defined a priori as a supermajority (67%) vote. An independent committee of experts external to the nomenclature process made the final recommendation on the acronym and its diagnostic criteria. A total of 236 panelists from 56 countries participated in 4 online surveys and 2 hybrid meetings. Response rates across the 4 survey rounds were 87%, 83%, 83%, and 78%, respectively. Seventy-four percent of respondents felt that the current nomenclature was sufficiently flawed to consider a name change. The terms “nonalcoholic” and “fatty” were felt to be stigmatising by 61% and 66% of respondents, respectively. Steatotic liver disease was chosen as an overarching term to encompass the various aetiologies of steatosis. The term steatohepatitis was felt to be an important pathophysiological concept that should be retained. The name chosen to replace NAFLD was metabolic dysfunction–associated steatotic liver disease. There was consensus to change the definition to include the presence of at least 1 of 5 cardiometabolic risk factors. Those with no metabolic parameters and no known cause were deemed to have cryptogenic steatotic liver disease. A new category, outside pure metabolic dysfunction–associated steatotic liver disease, termed metabolic and alcohol related/associated liver disease (MetALD), was selected to describe those with metabolic dysfunction–associated steatotic liver disease, who consume greater amounts of alcohol per week (140–350 g/wk and 210–420 g/wk for females and males, respectively). The new nomenclature and diagnostic criteria are widely supported and nonstigmatising, and can improve awareness and patient identification.

ABSTRACTBackground:The relations between hepatic steatosis and histological features of hepatocyte injury in children with nonalcoholic fatty liver disease have yet to be examined. The aims of the present study were to establish associations between steatosis amount, type, and distribution in a well‐characterized group of children with biopsy‐proven nonalcoholic fatty liver disease (NAFLD).Patients and Methods:One hundred eight children with NAFLD seen in 5 centers were studied. Clinical and laboratory data were collected. Hematoxylin‐eosin and Masson trichrome stains were evaluated by 2 expert liver pathologists. Steatosis grade (0–3), type (macrovesicular, microvesicular, or mixed), and zone (1, 3, azonal, or panacinar) were determined. The NAFLD activity score and fibrosis stage were determined.Results:Median patient age was 12 years and median body mass index was 31 kg/m2. Fibrosis was present in 87%. The median NAFLD activity score was 4. Mild, moderate, and severe steatosis were present in 42%, 34%, and 24% of biopsies, respectively. Macrovesicular steatosis was present in 81% and mixed steatosis was present in 19%. Panacinar distribution of steatosis was most frequent (40%), followed by azonal (27%). Steatosis grade positively correlated with portal inflammation (P = 0.018). Azonal distribution positively correlated with presence of hepatocyte ballooning (P = 0.03). Biopsies with mixed steatosis were approximately 20 times more likely to have megamitochondria than those with macrovesicular steatosis alone (95% confidence interval 2.3–204.9). There was no relation between steatosis amount, type, or distribution to fibrosis stage.Conclusions:Specific histological patterns of steatosis in children are associated with histological markers of steatohepatitis. Ballooning and portal inflammation correlated well with features of steatosis.