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Pediatric non-alcoholic fatty liver disease: Recent solutions, unresolved issues, and future research directions.
World J Gastroenterol 2016; 22(36):8078-93WJ

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.

Authors+Show Affiliations

Maria Grazia Clemente, Pediatric Clinic, Department of Surgical, Microsurgical and Medical Sciences, University of Sassari, 07100 Sassari, Italy.Maria Grazia Clemente, Pediatric Clinic, Department of Surgical, Microsurgical and Medical Sciences, University of Sassari, 07100 Sassari, Italy.Maria Grazia Clemente, Pediatric Clinic, Department of Surgical, Microsurgical and Medical Sciences, University of Sassari, 07100 Sassari, Italy.Maria Grazia Clemente, Pediatric Clinic, Department of Surgical, Microsurgical and Medical Sciences, University of Sassari, 07100 Sassari, Italy.

Pub Type(s)

Journal Article
Review

Language

eng

PubMed ID

27688650

Citation

Clemente, Maria Grazia, et al. "Pediatric Non-alcoholic Fatty Liver Disease: Recent Solutions, Unresolved Issues, and Future Research Directions." World Journal of Gastroenterology, vol. 22, no. 36, 2016, pp. 8078-93.
Clemente MG, Mandato C, Poeta M, et al. Pediatric non-alcoholic fatty liver disease: Recent solutions, unresolved issues, and future research directions. World J Gastroenterol. 2016;22(36):8078-93.
Clemente, M. G., Mandato, C., Poeta, M., & Vajro, P. (2016). Pediatric non-alcoholic fatty liver disease: Recent solutions, unresolved issues, and future research directions. World Journal of Gastroenterology, 22(36), pp. 8078-93. doi:10.3748/wjg.v22.i36.8078.
Clemente MG, et al. Pediatric Non-alcoholic Fatty Liver Disease: Recent Solutions, Unresolved Issues, and Future Research Directions. World J Gastroenterol. 2016 Sep 28;22(36):8078-93. PubMed PMID: 27688650.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Pediatric non-alcoholic fatty liver disease: Recent solutions, unresolved issues, and future research directions. AU - Clemente,Maria Grazia, AU - Mandato,Claudia, AU - Poeta,Marco, AU - Vajro,Pietro, PY - 2013/06/30/received PY - 2016/08/04/revised PY - 2016/08/23/accepted PY - 2016/10/1/entrez PY - 2016/10/1/pubmed PY - 2017/5/20/medline KW - Childhood obesity KW - Hepatic metabolic syndrome KW - Non-alcoholic fatty liver disease KW - Non-alcoholic fatty liver disease diagnosis KW - Non-alcoholic steatohepatitis SP - 8078 EP - 93 JF - World journal of gastroenterology JO - World J. Gastroenterol. VL - 22 IS - 36 N2 - 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. SN - 2219-2840 UR - https://www.unboundmedicine.com/medline/citation/27688650/Pediatric_non_alcoholic_fatty_liver_disease:_Recent_solutions_unresolved_issues_and_future_research_directions_ L2 - http://www.wjgnet.com/1007-9327/full/v22/i36/8078.htm DB - PRIME DP - Unbound Medicine ER -