Nonalcoholic Fatty Liver Disease in Children: Unique Considerations and Challenges

Goldner, Dana; Lavine, Joel E.

doi:10.1053/j.gastro.2020.01.048

Cited by 87 publications

(101 citation statements)

References 182 publications

(178 reference statements)

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“…Although NAFLD has epidemic proportions in adults, children are not spared either [167]. Additionally, pediatric NAFLD has distinctive histological and pathogenic features, and is an ever escalating cause of chronic liver disease, with the potential of impacting health outcomes in adolescents and young adults [168]. This justifies the publication of NAFLD guidelines from pediatric scientific societies.…”

Section: History Of Guidelines On Nafld Issued By Scientific Societiesmentioning

confidence: 99%

History of Nonalcoholic Fatty Liver Disease

Lonardo¹,

Leoni

Alswat

et al. 2020

IJMS

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Based on the assumption that characterizing the history of a disease will help in improving practice while offering a clue to research, this article aims at reviewing the history of nonalcoholic fatty liver disease (NAFLD) in adults and children. To this end, we address the history of NAFLD histopathology, which begins in 1980 with Ludwig’s seminal studies, although previous studies date back to the 19th century. Moreover, the principal milestones in the definition of genetic NAFLD are summarized. Next, a specific account is given of the evolution, over time, of our understanding of the association of NAFLD with metabolic syndrome, spanning from the outdated concept of “NAFLD as a manifestation of the Metabolic Syndrome”, to the more appropriate consideration that NAFLD has, with metabolic syndrome, a mutual and bi-directional relationship. In addition, we also report on the evolution from first intuitions to more recent studies, supporting NAFLD as an independent risk factor for cardiovascular disease. This association probably has deep roots, going back to ancient Middle Eastern cultures, wherein the liver had a significance similar to that which the heart holds in contemporary society. Conversely, the notions that NAFLD is a forerunner of hepatocellular carcinoma and extra-hepatic cancers is definitely more modern. Interestingly, guidelines issued by hepatological societies have lagged behind the identification of NAFLD by decades. A comparative analysis of these documents defines both shared attitudes (e.g., ultrasonography and lifestyle changes as the first approaches) and diverging key points (e.g., the threshold of alcohol consumption, screening methods, optimal non-invasive assessment of liver fibrosis and drug treatment options). Finally, the principal historical steps in the general, cellular and molecular pathogenesis of NAFLD are reviewed. We conclude that an in-depth understanding of the history of the disease permits us to better comprehend the disease itself, as well as to anticipate the lines of development of future NAFLD research.

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Section: History Of Guidelines On Nafld Issued By Scientific Societiesmentioning

confidence: 99%

History of Nonalcoholic Fatty Liver Disease

Lonardo¹,

Leoni

Alswat

et al. 2020

IJMS

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“…The trends in NAFLD incidence were followed for 17 years in a US community, finding that the incidence of NAFLD increased 5-fold, and even more (7-fold) in young adults [ 3 ]. Importantly, due to the growing increase in childhood obesity and children presenting greater vulnerability to genetic and environmental factors, NAFLD is now affecting up to 20% of the general pediatric population [ 4 , 5 ]. NAFLD in non-obese patients, so-called lean NAFLD, is also increasing, particularly in Asian patients [ 6 ].…”

Section: Nafldmentioning

confidence: 99%

Peroxisome Proliferator-Activated Receptors and Their Novel Ligands as Candidates for the Treatment of Non-Alcoholic Fatty Liver Disease

Fougerat

Montagner

Loiseau

et al. 2020

Cells

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Non-alcoholic fatty liver disease (NAFLD) is a major health issue worldwide, frequently associated with obesity and type 2 diabetes. Steatosis is the initial stage of the disease, which is characterized by lipid accumulation in hepatocytes, which can progress to non-alcoholic steatohepatitis (NASH) with inflammation and various levels of fibrosis that further increase the risk of developing cirrhosis and hepatocellular carcinoma. The pathogenesis of NAFLD is influenced by interactions between genetic and environmental factors and involves several biological processes in multiple organs. No effective therapy is currently available for the treatment of NAFLD. Peroxisome proliferator-activated receptors (PPARs) are nuclear receptors that regulate many functions that are disturbed in NAFLD, including glucose and lipid metabolism, as well as inflammation. Thus, they represent relevant clinical targets for NAFLD. In this review, we describe the determinants and mechanisms underlying the pathogenesis of NAFLD, its progression and complications, as well as the current therapeutic strategies that are employed. We also focus on the complementary and distinct roles of PPAR isotypes in many biological processes and on the effects of first-generation PPAR agonists. Finally, we review novel and safe PPAR agonists with improved efficacy and their potential use in the treatment of NAFLD.

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“…In adults, steatosis, inflammation, and accumulation of collagen start in the perivenular area (zone 3), while in children, it usually starts in the periportal area (zone 1) with lack of ballooning (22). However, it is not clear whether patients with pediatric MAFLD pattern differ in pathogenesis, prognosis, or response to treatment (23). In addition, due to lack of long-term follow-up from children to adults, the natural history and prognosis of MAFLD in children are still uncertain.…”

Section: Introductionmentioning

confidence: 99%

New Perspectives on Genetic Prediction for Pediatric Metabolic Associated Fatty Liver Disease

Lin

2020

Front. Pediatr.

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Non-alcoholic or recently re-defined metabolic associated fatty liver disease (MAFLD), a spectrum of progressive hepatic disease, has become a public health issue in obese children and adolescents. MAFLD is a complex metabolic disease strongly associated with obesity and insulin resistance. It is not known why not every obese subject will develop MAFLD. Different ethnic/racial groups display differences in MAFLD prevalence, indicating genetic factor plays a role. In the past two decades, sequence variations in genetic loci, including PNPLA3, TM6SF2, GCKR, MBOAT7, HSD17B13, etc. have been shown to confer susceptibility to MAFLD in children and adults. This review article provides an updated viewpoint of genetic predictors related to pediatric MAFLD. We discuss whether these susceptible genes can be clinically used for risk stratification and personalized care. Understanding human genetics and molecular mechanisms can give important information not only for prediction of risk but also on how to design drugs. In view of current epidemic of MAFLD worldwide, it is necessary to identify which children with MAFLD progress rapidly and need earlier intervention. In the future, a comprehensive analysis of individualized genetic and environmental factors may help assess the risk of children with MAFLD and personalize their treatment.

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Nonalcoholic Fatty Liver Disease in Children: Unique Considerations and Challenges

Cited by 87 publications

References 182 publications

History of Nonalcoholic Fatty Liver Disease

History of Nonalcoholic Fatty Liver Disease

Peroxisome Proliferator-Activated Receptors and Their Novel Ligands as Candidates for the Treatment of Non-Alcoholic Fatty Liver Disease

New Perspectives on Genetic Prediction for Pediatric Metabolic Associated Fatty Liver Disease

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