Childhood and Adolescent Nonalcoholic Fatty Liver Disease: Is It Different from Adults?

Fitzpatrick, Emer; Dhawan, Anil

doi:10.1016/j.jceh.2019.05.005

Cited by 26 publications

(23 citation statements)

References 66 publications

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“…This meta‐analysis addressed the effects of the PNPLA3 I148M polymorphism on NAFLD in paediatric and adolescent populations, whose histological features are different from those of the adult NAFLD populations . On the basis of pooled estimates, not only was the influence of the I148M variant on NAFLD susceptibility and severity determined but also its impact on metabolic comorbidities was quantitatively elucidated.…”

Section: Discussionmentioning

confidence: 99%

Effect of the patatin‐like phospholipase domain containing 3 gene (PNPLA3) I148M polymorphism on the risk and severity of nonalcoholic fatty liver disease and metabolic syndromes: A meta‐analysis of paediatric and adolescent individuals

Hua

Rui

et al. 2020

Pediatric Obesity

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Background: The effect of the patatin-like phospholipase domain containing 3 gene (PNPLA3) I148M polymorphism on the risk and severity of paediatric and adolescent nonalcoholic fatty liver disease (NAFLD) remains inconclusive.Objectives: We aimed to estimate the effect of this polymorphism not only on earlyonset NAFLD risk and severity but also on metabolic syndromes susceptibility.Methods: A systematic literature search was performed to identify relevant datasets.The odds ratio of the dichotomic variables and the standardized mean difference of quantitative variables with corresponding 95% confidence intervals were calculated to assess the strength of the associations.Results: Twenty-seven studies comprising 10 070 subjects were eligible. The summary effect showed that this polymorphism increased susceptibility to NAFLD development. Furthermore, it also indicated that nonalcoholic steatohepatitis (NASH) was more frequently observed in G allele carriers among paediatric and adolescent NAFLD patients. Moreover, the meta-analysis suggested that the variant was significantly associated with elevated liver damage indexes, including serum alanine transaminase, aspartate transaminase, gamma-glutamyltransferase concentrations, and liver fat content. However, the summary estimates for insulin resistance, lipid metabolism, and adiposity showed no significant associations. Conclusions:The PNPLA3 I148M polymorphism is associated with elevated earlyonset NAFLD risk, severity, and liver damage but not with related metabolic syndromes.

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Section: Discussionmentioning

confidence: 99%

Effect of the patatin‐like phospholipase domain containing 3 gene (PNPLA3) I148M polymorphism on the risk and severity of nonalcoholic fatty liver disease and metabolic syndromes: A meta‐analysis of paediatric and adolescent individuals

Hua

Rui

et al. 2020

Pediatric Obesity

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“…compared with other datasets that analyzed adults [10]. As we know, NAFLD in adolescents is different from that in adults [11]. In this study, the three microarray datasets including GSE48452, GSE63067 and GSE89632…”

Section: Introductionmentioning

confidence: 95%

Identification of Shared Gene Signatures in Different Stages of Non-Alcoholic Fatty Liver Disease Using Integrated Microarray Dataset

Gh¹,

Arabfard²

2020

Preprint

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Purpose: Non-alcoholic fatty liver disease (NAFLD) is the most preventable type of chronic liver disease worldwide and a risk factor for developing cirrhosis or hepatocellular carcinoma (HCC) if untreated. Although experts have performed lots of efforts to find the underlying mechanisms of NAFLD, it remains a challenge to recognize them. The aim of this study is to distinguish common gene signature and pathways in the human liver during NAFLD progression through the systems biology method.Methods: In this study, the three microarray datasets, GSE48452, GSE63067 and GSE89632, were selected from the NCBI GEO database to explore differentially expressed genes (DEGs) among healthy controls, simple steatosis and non-alcoholic steatohepatitis (NASH) patients. Furthermore, protein-protein interaction (PPI) networks and pathway enrichment analysis were used to detect common genes and biological pathways in different stages of NAFLD.Results: The current study was included 47 healthy subjects, 36 patients with simple steatosis and 46 NASH patients. Common high degree genes among all three sets were CHI3L1, GFBP2, NRG1, PEG10 and FADS2. The top five genes in the hepatic PPI networks of three datasets were STAT3, JUN, CANX, FN1 and MYC. Signal transduction, immune response, and anti-apoptosis were the most important biological pathways between healthy vs. NASH, while cell communication, signal transduction and immune response were three top biological pathways between healthy vs. simple steatosis. Also, the most eminent biological pathways between NASH vs. simple steatosis were metabolism and energy pathways. Conclusion: The present study represented the unique and shared key genes and pathways between different stages of NAFLD, which may facilitate the understanding of the NAFLD mechanism and identify potential therapeutic targets in this disease.

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“…Diet is shown to act as a risk factor in pediatric NAFLD [9]. Nevertheless, it is unclear which dietary components affect the development and progression of NAFLD in children [10].…”

Section: Introductionmentioning

confidence: 99%

“…Nevertheless, it is unclear which dietary components affect the development and progression of NAFLD in children [10]. Based on epidemiological data, obese children with NAFLD seem to have higher intakes of fructose, saturated fat, as well as the lower fiber intakes compared to those without NAFLD [9,11]. Concerning dietary patterns, in a population-based cohort study of adolescents, a close adherence in a Western dietary pattern at 14 years was associated with an increased risk of NAFLD at 17 years, an association that was dependent on BMI [12].…”

Section: Introductionmentioning

confidence: 99%

Effects of Dietary and Lifestyle Interventions on Liver, Clinical and Metabolic Parameters in Children and Adolescents with Non-Alcoholic Fatty Liver Disease: A Systematic Review

et al. 2020

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Non-alcoholic fatty liver disease (NAFLD) affects 5.5–10.3% of children worldwide, while in obese individuals, it increases to almost 34%. Pediatric NAFLD is consistently associated with metabolic syndrome and insulin resistance. As no pharmacological agents exist for the treatment of NAFLD, lifestyle modifications remain the only therapy. However, as not all overweight/obese children have NAFLD, high-quality data, focused exclusively on NAFLD population are needed. Therefore, the present systematic review assessed the efficacy of lifestyle (diet or exercise) based on randomized controlled clinical trials (RCTs) on liver, anthropometric, glucose, and lipid parameters in children, with imaging or biopsy-proven NAFLD. In general, the results were inconclusive and therefore no specific recommendations could be drawn. In most studies, differences were derived from within group comparisons, which are known to be highly misleading. However, both low-carbohydrate and low-fat diets could benefit liver outcomes, as long as weight loss is achieved, but not necessary glucose and lipid parameters. No RCTs were found on exercise alone, as compared to no intervention on pediatric NAFLD. Concerning diet plus exercise interventions, all studies led to improvements in liver outcomes accompanied with weight loss. Resolution of NAFLD was found in considerably high percentages, while improvements were also seen in glucose but were modest in lipid parameters.

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Childhood and Adolescent Nonalcoholic Fatty Liver Disease: Is It Different from Adults?

Cited by 26 publications

References 66 publications

Effect of the patatin‐like phospholipase domain containing 3 gene (PNPLA3) I148M polymorphism on the risk and severity of nonalcoholic fatty liver disease and metabolic syndromes: A meta‐analysis of paediatric and adolescent individuals

Effect of the patatin‐like phospholipase domain containing 3 gene (PNPLA3) I148M polymorphism on the risk and severity of nonalcoholic fatty liver disease and metabolic syndromes: A meta‐analysis of paediatric and adolescent individuals

Identification of Shared Gene Signatures in Different Stages of Non-Alcoholic Fatty Liver Disease Using Integrated Microarray Dataset

Effects of Dietary and Lifestyle Interventions on Liver, Clinical and Metabolic Parameters in Children and Adolescents with Non-Alcoholic Fatty Liver Disease: A Systematic Review

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