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Challenges in the diagnosis of NASH
PEDIATRIC NASH: IS IT DIFFERENT AND SHOULD WE
LOOK FOR IT?
Valerio Nobili
Hepatometabolic Department and Liver Research Unit,
Bambino Gesù Children’s Hospital,
Rome, Italy
Email: nobili66@yahoo.it
Take home messages
• NAFLD has rapidly become the leading cause of chronic hepatopathies in children. Considering the
strict association between NAFLD, MetS and CVD this scenario appears particularly worrisome.
• Genetic analyses may aid the identification of children susceptible to NAFLD/NASH.
• Non-invasive tools to diagnose NAFLD in children could greatly reduce the need for liver biopsy.
• To date none of the available drugs has been shown to be effective in totally reversing NAFLD-
related liver damage.
• Adequate diagnostic and therapeutic management is crucial to prevent and counteract progression
of pediatric NAFLD.
Introduction: epidemiology and pathogenesis
NAFLD now represents the most frequent cause of chronic liver disease in industrialized countries in
children and adolescents, as a direct consequence of the rise in childhood obesity. Although the exact
prevalence of NAFLD in the pediatric setting is still unknown, recent epidemiological data indicate
a prevalence of 3-10% in the general pediatric population. Prevalence increases up to >70%, with a
male-to-female ratio of 2:1, in obese children [1]. The term NAFLD encompasses a broad spectrum of
diverse liver conditions. The histological features of NAFLD vary from fat accumulation in >5% of the
hepatocytes (simple hepatic steatosis) to NASH with necroinflammation (sometimes associated with
fibrosis), which in turn can progress to cirrhosis and hepatocellular carcinoma during early adolescence.
The pathogenesis of NAFLD appears to be multifactorial, involving both genetic and environmental
factors. In fact, although pediatric NAFLD is generally related to a sedentary lifestyle and hyper-
caloric diet leading to a progressive increase of body mass index (BMI) and visceral adiposity, recent
epidemiological, familial, and twins studies suggested a strong heritability for NAFLD [2]. Several
genetic studies have demonstrated that single nucleotide polymorphisms (SNPs) in genes involved in
lipid metabolism, oxidative stress, insulin signalling and fibrogenesis have been associated with a high
risk for NAFLD development and progression [3]. In a recent study, Nobili et al. have described a
multivariate logistic model based on four polymorphisms, which allowed a NASH risk score in obese
children with increased liver enzymes to be extrapolated [3].
The complex interplay between genes and environment in NAFLD pathogenesis is sustained by multiple
mechanisms that involve liver interactions with other organs and tissues, especially gut (the so-called
‘gut-liver axis’) and adipose tissue.
The International Liver Congress™ 2015 • Vienna, Austria • April 22–23, 2015 31
PEDIATRIC NASH: IS IT DIFFERENT AND SHOULD WE
LOOK FOR IT?
Valerio Nobili
Hepatometabolic Department and Liver Research Unit,
Bambino Gesù Children’s Hospital,
Rome, Italy
Email: nobili66@yahoo.it
Take home messages
• NAFLD has rapidly become the leading cause of chronic hepatopathies in children. Considering the
strict association between NAFLD, MetS and CVD this scenario appears particularly worrisome.
• Genetic analyses may aid the identification of children susceptible to NAFLD/NASH.
• Non-invasive tools to diagnose NAFLD in children could greatly reduce the need for liver biopsy.
• To date none of the available drugs has been shown to be effective in totally reversing NAFLD-
related liver damage.
• Adequate diagnostic and therapeutic management is crucial to prevent and counteract progression
of pediatric NAFLD.
Introduction: epidemiology and pathogenesis
NAFLD now represents the most frequent cause of chronic liver disease in industrialized countries in
children and adolescents, as a direct consequence of the rise in childhood obesity. Although the exact
prevalence of NAFLD in the pediatric setting is still unknown, recent epidemiological data indicate
a prevalence of 3-10% in the general pediatric population. Prevalence increases up to >70%, with a
male-to-female ratio of 2:1, in obese children [1]. The term NAFLD encompasses a broad spectrum of
diverse liver conditions. The histological features of NAFLD vary from fat accumulation in >5% of the
hepatocytes (simple hepatic steatosis) to NASH with necroinflammation (sometimes associated with
fibrosis), which in turn can progress to cirrhosis and hepatocellular carcinoma during early adolescence.
The pathogenesis of NAFLD appears to be multifactorial, involving both genetic and environmental
factors. In fact, although pediatric NAFLD is generally related to a sedentary lifestyle and hyper-
caloric diet leading to a progressive increase of body mass index (BMI) and visceral adiposity, recent
epidemiological, familial, and twins studies suggested a strong heritability for NAFLD [2]. Several
genetic studies have demonstrated that single nucleotide polymorphisms (SNPs) in genes involved in
lipid metabolism, oxidative stress, insulin signalling and fibrogenesis have been associated with a high
risk for NAFLD development and progression [3]. In a recent study, Nobili et al. have described a
multivariate logistic model based on four polymorphisms, which allowed a NASH risk score in obese
children with increased liver enzymes to be extrapolated [3].
The complex interplay between genes and environment in NAFLD pathogenesis is sustained by multiple
mechanisms that involve liver interactions with other organs and tissues, especially gut (the so-called
‘gut-liver axis’) and adipose tissue.
The International Liver Congress™ 2015 • Vienna, Austria • April 22–23, 2015 31
