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Pediatric non-alcoholic fatty liver disease: Recent solutions, unresolved issues, and future research directions

View Article: PubMed Central - PubMed

ABSTRACT

Non-alcoholic fatty liver disease (NAFLD) in children is becoming a major health concern. A “multiple-hit” pathogenetic model has been suggested to explain the progressive liver damage that occurs among children with NAFLD. In addition to the accumulation of fat in the liver, insulin resistance (IR) and oxidative stress due to genetic/epigenetic background, unfavorable lifestyles, gut microbiota and gut-liver axis dysfunction, and perturbations of trace element homeostasis have been shown to be critical for disease progression and the development of more severe inflammatory and fibrotic stages [non-alcoholic steatohepatitis (NASH)]. Simple clinical and laboratory parameters, such as age, history, anthropometrical data (BMI and waist circumference percentiles), blood pressure, surrogate clinical markers of IR (acanthosis nigricans), abdominal ultrasounds, and serum transaminases, lipids and glucose/insulin profiles, allow a clinician to identify children with obesity and obesity-related conditions, including NAFLD and cardiovascular and metabolic risks. A liver biopsy (the “imperfect” gold standard) is required for a definitive NAFLD/NASH diagnosis, particularly to exclude other treatable conditions or when advanced liver disease is expected on clinical and laboratory grounds and preferably prior to any controlled trial of pharmacological/surgical treatments. However, a biopsy clearly cannot represent a screening procedure. Advancements in diagnostic serum and imaging tools, especially for the non-invasive differentiation between NAFLD and NASH, have shown promising results, e.g., magnetic resonance elastography. Weight loss and physical activity should be the first option of intervention. Effective pharmacological treatments are still under development; however, drugs targeting IR, oxidative stress, proinflammatory pathways, dyslipidemia, gut microbiota and gut liver axis dysfunction are an option for patients who are unable to comply with the recommended lifestyle changes. When morbid obesity prevails, bariatric surgery should be considered.

No MeSH data available.


Related in: MedlinePlus

Simplified cartoon of the multiple pathomechanisms involved in development and progression of non-alcoholic fatty liver disease, and proposed stepwise treatment options. NAFLD: Non-alcoholic fatty liver disease; NASH: Non-alcoholic steato-hepatitis; FXR: Farnesoid X receptor; AT: Adipose tissue.
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Figure 1: Simplified cartoon of the multiple pathomechanisms involved in development and progression of non-alcoholic fatty liver disease, and proposed stepwise treatment options. NAFLD: Non-alcoholic fatty liver disease; NASH: Non-alcoholic steato-hepatitis; FXR: Farnesoid X receptor; AT: Adipose tissue.

Mentions: Lifestyle interventions (i.e., diet and exercise) represent the mainstay treatment; however, compliance in both adults and children is poor. Research on the pathogenesis, genetic markers, and the role of gut microbiome in NAFLD has led to development of several medical and surgical therapeutic approaches. Figure 1 summarizes the currently available information.


Pediatric non-alcoholic fatty liver disease: Recent solutions, unresolved issues, and future research directions
Simplified cartoon of the multiple pathomechanisms involved in development and progression of non-alcoholic fatty liver disease, and proposed stepwise treatment options. NAFLD: Non-alcoholic fatty liver disease; NASH: Non-alcoholic steato-hepatitis; FXR: Farnesoid X receptor; AT: Adipose tissue.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC5037077&req=5

Figure 1: Simplified cartoon of the multiple pathomechanisms involved in development and progression of non-alcoholic fatty liver disease, and proposed stepwise treatment options. NAFLD: Non-alcoholic fatty liver disease; NASH: Non-alcoholic steato-hepatitis; FXR: Farnesoid X receptor; AT: Adipose tissue.
Mentions: Lifestyle interventions (i.e., diet and exercise) represent the mainstay treatment; however, compliance in both adults and children is poor. Research on the pathogenesis, genetic markers, and the role of gut microbiome in NAFLD has led to development of several medical and surgical therapeutic approaches. Figure 1 summarizes the currently available information.

View Article: PubMed Central - PubMed

ABSTRACT

Non-alcoholic fatty liver disease (NAFLD) in children is becoming a major health concern. A “multiple-hit” pathogenetic model has been suggested to explain the progressive liver damage that occurs among children with NAFLD. In addition to the accumulation of fat in the liver, insulin resistance (IR) and oxidative stress due to genetic/epigenetic background, unfavorable lifestyles, gut microbiota and gut-liver axis dysfunction, and perturbations of trace element homeostasis have been shown to be critical for disease progression and the development of more severe inflammatory and fibrotic stages [non-alcoholic steatohepatitis (NASH)]. Simple clinical and laboratory parameters, such as age, history, anthropometrical data (BMI and waist circumference percentiles), blood pressure, surrogate clinical markers of IR (acanthosis nigricans), abdominal ultrasounds, and serum transaminases, lipids and glucose/insulin profiles, allow a clinician to identify children with obesity and obesity-related conditions, including NAFLD and cardiovascular and metabolic risks. A liver biopsy (the “imperfect” gold standard) is required for a definitive NAFLD/NASH diagnosis, particularly to exclude other treatable conditions or when advanced liver disease is expected on clinical and laboratory grounds and preferably prior to any controlled trial of pharmacological/surgical treatments. However, a biopsy clearly cannot represent a screening procedure. Advancements in diagnostic serum and imaging tools, especially for the non-invasive differentiation between NAFLD and NASH, have shown promising results, e.g., magnetic resonance elastography. Weight loss and physical activity should be the first option of intervention. Effective pharmacological treatments are still under development; however, drugs targeting IR, oxidative stress, proinflammatory pathways, dyslipidemia, gut microbiota and gut liver axis dysfunction are an option for patients who are unable to comply with the recommended lifestyle changes. When morbid obesity prevails, bariatric surgery should be considered.

No MeSH data available.


Related in: MedlinePlus