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World J Gastroenterol. Jul 21, 2014; 20(27): 9055-9071
Published online Jul 21, 2014. doi: 10.3748/wjg.v20.i27.9055
Nonalcoholic fatty liver disease and the heart in children and adolescents
Lucia Pacifico, Claudio Chiesa, Caterina Anania, Antonio De Merulis, John Frederick Osborn, Sara Romaggioli, Eugenio Gaudio
Lucia Pacifico, Caterina Anania, Antonio De Merulis, Sara Romaggioli, Department of Pediatrics and Child Neuropsychiatry, Sapienza University of Rome, 00161 Rome, Italy
Claudio Chiesa, Institute of Translational Pharmacology, National Research Council, 00133 Rome, Italy
John Frederick Osborn, Department of Public Health and Infectious Diseases, Sapienza University of Rome, 00161 Rome, Italy
Eugenio Gaudio, Department of Human Anatomy, Histology, Forensic Medicine and Orthopedics Sciences, Sapienza University of Rome, 00161 Rome, Italy
Author contributions: Pacifico L, Chiesa C, Osborn JF and Gaudio E designed the study, analyzed the data and wrote the manuscript; Anania C, De Merulis A and Romaggioli S collected the data; all the authors participated in the critical review and in the final approval of the manuscript.
Correspondence to: Claudio Chiesa, MD, Institute of Translational Pharmacology, National Research Council, Via Fosso del Cavaliere, 100, 00133-Rome, Italy. claudio.chiesa@ift.cnr.it
Telephone: +39-6-49979215 Fax: +39-6-49979216
Received: November 26, 2013
Revised: February 7, 2014
Accepted: May 12, 2014
Published online: July 21, 2014
Abstract

Over the last two decades, the rise in the prevalence rates of overweight and obesity explains the emergence of nonalcoholic fatty liver disease (NAFLD) as the leading cause of chronic liver disease worldwide. As described in adults, children and adolescents with fatty liver display insulin resistance, glucose intolerance, and dyslipidemia. Thus NAFLD has emerged as the hepatic component of the metabolic syndrome (MetS) and a strong cardiovascular risk factor even at a very early age. Several studies, including pediatric populations, have reported independent associations between NAFLD and markers of subclinical atherosclerosis including impaired flow-mediated vasodilation, increased carotid artery intima-media thickness, and arterial stiffness, after adjusting for cardiovascular risk factors and MetS. Also, it has been shown that NAFLD is associated with cardiac alterations, including abnormal left ventricular structure and impaired diastolic function. The duration of these subclinical abnormalities may be important, because treatment to reverse the process is most likely to be effective earlier in the disease. In the present review, we examine the current evidence on the association between NAFLD and atherosclerosis as well as between NAFLD and cardiac dysfunction in the pediatric population, and discuss briefly the possible biological mechanisms linking NAFLD and cardiovascular changes. We also address the approach to treatment for this increasingly prevalent disease, which is likely to have an important future global impact on the burden of ill health, to prevent not only end-stage liver disease but also cardiovascular disease.

Keywords: Nonalcoholic fatty liver disease, Children, Atherosclerosis, Cardiac structure, Cardiac function

Core tip: Nonalcoholic fatty liver disease (NAFLD) is an important and emerging health problem in childhood. It is recognized as part of the metabolic syndrome and especially the necroinflammatory form is associated with a high risk for the development of functional and structural vascular changes as well as left ventricular dysfunction at an early age. In addition, there seems to be a complex bidirectional relationship between the progression to nonalcoholic steatohepatitis (NASH) and the development of insulin resistance and cardiovascular abnormalities. Early intervention during childhood to recognize NAFLD, as well as to prevent its progression to NASH, may be a crucial step in averting an unfavorable cardiac phenotype.