Pediatric non-alcoholic fatty liver disease: Recent solutions, unresolved issues, and future research directions.
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.
Maria Grazia Clemente, Pediatric Clinic, Department of Surgical, Microsurgical and Medical Sciences, University of Sassari, 07100 Sassari, Italy.
Maria Grazia
MG
Clemente
Maria Grazia Clemente, Pediatric Clinic, Department of Surgical, Microsurgical and Medical Sciences, University of Sassari, 07100 Sassari, Italy.
Claudia
C
Mandato
Maria Grazia Clemente, Pediatric Clinic, Department of Surgical, Microsurgical and Medical Sciences, University of Sassari, 07100 Sassari, Italy.
Marco
M
Poeta
Maria Grazia Clemente, Pediatric Clinic, Department of Surgical, Microsurgical and Medical Sciences, University of Sassari, 07100 Sassari, Italy.
Pietro
P
Vajro
D000273:Adipose Tissue / Q000378:metabolism; D000886:Anthropometry; D001794:Blood Pressure; D015992:Body Mass Index; D002648:Child; D002675:Child, Preschool; D003937:Diagnosis, Differential; D018450:Disease Progression; D000431:Ethanol / Q000737:chemistry; D005234:Fatty Liver / Q000175:diagnosis* / Q000628:therapy*; D000069196:Gastrointestinal Microbiome; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007249:Inflammation; D007333:Insulin Resistance; D007413:Intestinal Mucosa / Q000378:metabolism; D008019:Life Style; D008099:Liver / Q000378:metabolism / Q000473:pathology; D018977:Micronutrients / Q000378:metabolism; D065626:Non-alcoholic Fatty Liver Disease / Q000175:diagnosis* / Q000628:therapy*; D009765:Obesity; D018384:Oxidative Stress; D010372:Pediatrics; D014807:Vitamin D / Q000378:metabolism; D055105:Waist Circumference
D018977:Micronutrients; D014807:Vitamin D; D000431:Ethanol
Childhood obesity; Hepatic metabolic syndrome; Non-alcoholic fatty liver disease; Non-alcoholic fatty liver disease diagnosis; Non-alcoholic steatohepatitis
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