Perspectives on youth‐onset nonalcoholic fatty liver disease

Castillo‐Leon, Eduardo; Cioffi, Catherine E.; Vos, Miriam B.

doi:10.1002/edm2.184

Cited by 35 publications

(46 citation statements)

References 133 publications

(205 reference statements)

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“…Non-alcoholic fatty liver disease (NAFLD) has become the most common form of chronic liver disease in children and adolescents globally in recent years [ 1 ]. NAFLD in children is a major risk factor for the development of cirrhosis and hepatocellular carcinoma in adult [ 2 , 3 ], and it is also an early predictor of hypertension and type 2 diabetes [ 4 , 5 ]. Pregnancy is a critical period for fetal organ development [ 6 ], and maternal diet during pregnancy plays an important role in protecting against or exacerbating the offspring’s risk of developing NAFLD [ 7 , 8 ].…”

Section: Introductionmentioning

confidence: 99%

Perinatal High-Salt Diet Induces Gut Microbiota Dysbiosis, Bile Acid Homeostasis Disbalance, and NAFLD in Weanling Mice Offspring

et al. 2021

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A perinatal high-salt (HS) diet was reported to elevate plasma triglycerides. This study aimed to investigate the hypothesis that a perinatal HS diet predisposed offspring to non-alcoholic fatty liver disease (NAFLD), the hepatic manifestation of abnormal lipid metabolism, and the possible mechanism. Female C57BL/6 mice were fed a control diet (0.5% NaCl) or HS diet (4% NaCl) during pregnancy and lactation and their offspring were sacrificed at weaning. The perinatal HS diet induced greater variation in fecal microbial beta-diversity (β-diversity) and increased bacteria abundance of Proteobacteria and Bacteroides. The gut microbiota dysbiosis promoted bile acid homeostasis disbalance, characterized by the accumulation of lithocholic acid (LCA) and deoxycholic acid (DCA) in feces. These alterations disturbed gut barrier by increasing the expression of tight junction protein (Tjp) and occludin (Ocln), and increased systemic lipopolysaccharide (LPS) levels and hepatic inflammatory cytokine secretion (TNF-α and IL-6) in the liver. The perinatal HS diet also inhibited hepatic expression of hepatic FXR signaling (CYP7A1 and FXR), thus triggering increased hepatic expression of pro-inflammatory cytokines (TNF-α and IL-6) and hepatic lipid metabolism-associated genes (SREBP-1c, FAS, ACC), leading to unique characteristics of NAFLD. In conclusion, a perinatal HS diet induced NAFLD in weanling mice offspring; the possible mechanism was related to increased bacteria abundance of Proteobacteria and Bacteroides, increased levels of LCA and DCA in feces, and increased expressions of hepatic FXR signaling.

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Section: Introductionmentioning

confidence: 99%

Perinatal High-Salt Diet Induces Gut Microbiota Dysbiosis, Bile Acid Homeostasis Disbalance, and NAFLD in Weanling Mice Offspring

et al. 2021

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“…Non-alcoholic fatty liver disease (NAFLD) represents a heterogeneous and progressive condition with a major pathogenic interplay between both metabolic (e.g., obesity, insulin resistance) and genetic (e.g., PNPLA3 and TM6SF2) factors [ 1 ]. Parallel to the rising trend in obesity and diabetes, it has been increasingly recognized as the most common chronic liver disease both in adults and children, representing an enormous global health concern due to its cardiometabolic burden [ 2 , 3 , 4 ]. Over the past 20 years, accumulating evidence has indicated NAFLD as the hepatic manifestation of a systemic metabolic disorder [ 1 , 5 ].…”

Section: Introductionmentioning

confidence: 99%

“…Of concern, several studies have linked NAFLD to cardiometabolic derangements even in childhood [6]. Despite several promising researches investigating pharmacological approaches, to date no drug therapy for NAFLD has been licensed and lifestyle interventions remain the mainstay of this treatment [3].…”

Section: Introductionmentioning

confidence: 99%

MAFLD in Obese Children: A Challenging Definition

Sessa¹,

Guarino²,

Umano³

et al. 2021

Children

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Background: Recently, the new definition of Metabolic (dysfunction) associated fatty liver disease (MAFLD) has gained remarkable scientific interest. We aimed to evaluate the effectiveness of MAFLD definition in selecting obese children at higher cardiovascular risk. Methods: A total of 954 obese children and adolescents was retrospectively enrolled. Clinical, biochemical, and metabolic evaluations were performed. Hepatic steatosis was assessed by liver ultrasound. According to the metabolic status, the population was divided in three groups. Group 1 included obese patients without both non-alcoholic fatty liver disease (NAFLD) and metabolic dysregulation; group 2 included patients with obesity and NAFLD (then encompassing one MAFLD criterion); group 3 included patients with obesity, NAFLD and evidence of metabolic dysregulation (then encompassing more than 1 MAFLD criteria). Results: Patients of Group 3 showed a worse cardiometabolic profile, as also proven by the higher percentage of prediabetes (defined as the presence of impaired fasting glucose or impaired glucose tolerance) compared to other groups (p = 0.001). Conclusions: MAFLD criteria in obese children seem to be less accurate in identifying patients having an intrinsic higher cardiometabolic risk. This suggests the need for a more accurate definition in the context of pediatric obesity.

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“…A recent metanalysis performed in subjects aged 1 to 19 years reported a prevalence of FL of 2.3% in normal-weight, 12.5% in overweight, and 36.1% in obese children [ 2 ]. Even if the natural history of FL in children is largely unknown and cause–effect relationships between FL and associated diseases are hard to prove with the present evidence base [ 3 ], it is reasonable to assume that FL persisting from childhood to adulthood may have harmful hepatic and extrahepatic consequences [ 4 , 5 , 6 , 7 ].…”

Section: Introductionmentioning

confidence: 99%

Development and Internal Validation of Fatty Liver Prediction Models in Obese Children and Adolescents

Bedogni

Tamini

Caroli

et al. 2021

JCM

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To develop predictive models of fatty liver (FL), we performed a cross-sectional retrospective study of 1672 obese children with a median (interquartile range) age of 15 (13–16) years. The outcome variable was FL diagnosed by ultrasonography. The potential predictors were: (1) binary: sex; (2) continuous: age, body mass index (BMI), waist circumference (WC), alanine transaminase (ALT), aspartate transaminase, gamma-glutamyltransferase, glucose, insulin, homeostasis model assessment of insulin resistance (HOMA-IR), HDL-cholesterol, LDL-cholesterol, triglycerides, mean arterial pressure, uric acid, and c-reactive protein; (3) ordinal: Pubertal status. Bootstrapped multivariable logistic regression with fractional polynomials was used to develop the models. Two models were developed and internally validated, one using BMI and the other using WC as the anthropometric predictor. Both models included ALT, HOMA-IR, triglycerides, and uric acid as predictors, had similar discrimination (c-statistic = 0.81), and were similarly well calibrated as determined by calibration plots. These models should undergo external validation before being employed in clinical or research practice.

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Perspectives on youth‐onset nonalcoholic fatty liver disease

Cited by 35 publications

References 133 publications

Perinatal High-Salt Diet Induces Gut Microbiota Dysbiosis, Bile Acid Homeostasis Disbalance, and NAFLD in Weanling Mice Offspring

Perinatal High-Salt Diet Induces Gut Microbiota Dysbiosis, Bile Acid Homeostasis Disbalance, and NAFLD in Weanling Mice Offspring

MAFLD in Obese Children: A Challenging Definition

Development and Internal Validation of Fatty Liver Prediction Models in Obese Children and Adolescents

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