A 4‐Polymorphism Risk Score Predicts Steatohepatitis in Children With Nonalcoholic Fatty Liver Disease

“…A reduced SOD2 activity, by decreasing the liver's ability to detoxify mitochondrial superoxide anion, increases the susceptibility to oxidative stress, and NASH in obese children. 78 The interleukin 28B(IL28B) gene stimulates the expression of multiple genes encoding proinflammatory cytokines. The rs12979860 polymorphism of IL28B gene is associated with the severity of lobular inflammation and fibrosis.…”

Section: Molecular Geneticsmentioning

confidence: 99%

Epidemiological modifiers of non-alcoholic fatty liver disease: Focus on high-risk groups

Lonardo

Bellentani

Argo

et al. 2015

Digestive and Liver Disease

393

318

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We aimed to illustrate the epidemiology of nonalcoholic fatty liver disease in high-risk groups, which were identified based on existing literature. To this end, PubMed was searched to retrieve original articles published through May 2015 using relevant and pertinent keywords "nonalcoholic fatty liver disease" and "diabetes", "obesity", "hyperlipidemia", "familial heterozygous hypobelipoproteinemia", "hypertension", "metabolic syndrome", "ethnicity", "family history" or "genetic polymorphisms".We found that age, sex and ethnicity are major physiologic modifiers of the risk of nonalcoholic fatty liver disease, along with belonging to "nonalcoholic fatty liver disease families" and carrying risk alleles for selected genetic polymorphisms. Metabolic syndrome, diabetes, obesity, mixed hyperlipidaemia and hypocholesterolemia due to familial hypobetalipoproteinaemia are the major metabolic modifiers of nonalcoholic fatty liver disease risk. Compared to these metabolic conditions, however, arterial hypertension appears to carry a relatively more modest risk of nonalcoholic fatty liver disease.A better understanding of the epidemiology of nonalcoholic fatty liver disease may result in a more liberal policy of case finding among high-risk groups.

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“…Biopsy is also the gold-standard method to diagnose NASH and hepatic fibrosis. Recently, cytokeratin-18 fragment levels as well as a combined score made up of clinical variables and 5 polymorphisms have been proposed to identify obese children with NASH [63,64]. The paediatric NAFLD fibrosis index and transient elastography have both showed good accuracy in detecting hepatic fibrosis in children with NAFLD [65,66].…”

Section: Markers Of Co-morbiditiesmentioning

confidence: 99%

Predictors of Metabolic Risk in Childhood Obesity

Morandi

Maffeis²

2014

Horm Res Paediatr

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Most of the complications of juvenile obesity are due to metabolic disturbances induced by an excessive accumulation of fat which leads to chronic diseases like type 2 diabetes mellitus (T2DM) and cardiovascular disease (CVD). Finding effective ways of identifying obese paediatric patients who are at increased risk of developing cardiovascular and metabolic complications has been recognised to be a promising strategy to improve prevention of complications of early obesity. Moreover, correctly identifying obese children who are already affected by metabolic co-morbidities should be a clinical priority. According to the state of the art summarised in this review, traditional metabolic variables included in the definitions of metabolic syndrome (MS), pre-diabetes, non-alcoholic fatty liver disease (NAFLD)/non-alcoholic steato-hepatitis and, in obese girls, the presence of polycystic ovary syndrome are the best available longitudinal predictors of CVD and T2DM among obese children and adolescents. In clinical practice, traditional metabolic variables included in the definitions of MS should be assessed in all obese children and adolescents; fasting metabolic variables have been proposed to identify obese patients likely to be affected by impaired glucose tolerance or T2DM, and ultrasound has proved to be a valid surrogate for biopsy in the diagnosis of NAFLD. Further large longitudinal and cross-sectional studies are needed to improve our chances of identifying obese youth at the highest metabolic risk.

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A 4‐Polymorphism Risk Score Predicts Steatohepatitis in Children With Nonalcoholic Fatty Liver Disease

Abstract: A score based on genetic risk factors significantly predicts NASH in obese children with increased liver enzymes, representing a proof-of-principle that genetic scores may be useful to predict long-term outcomes of the disease and guide clinical management.

Cited by 78 publications

References 21 publications

EASL–EASD–EASO Clinical Practice Guidelines for the management of non-alcoholic fatty liver disease

EASL–EASD–EASO Clinical Practice Guidelines for the management of non-alcoholic fatty liver disease

Epidemiological modifiers of non-alcoholic fatty liver disease: Focus on high-risk groups

Predictors of Metabolic Risk in Childhood Obesity

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