Nonalcoholic Fatty Liver Disease and Carotid Atherosclerosis in Children

Pediatric Research, Apr 2008

Nonalcoholic fatty liver disease (NAFLD) is closely associated with several metabolic syndrome features, including obesity, dyslipidemia, insulin resistance, and increased cardiovascular risk. The present study was undertaken to assess whether NAFLD in children is associated with increased carotid artery intima-media thickness (IMT), a marker of early-generalized atherosclerosis. We analyzed carotid IMT along with serum triglycerides, total, low-density lipoprotein and high-density lipoprotein cholesterol, glucose, insulin, insulin resistance index (as homeostasis model assessment of insulin resistance), aminotransferases, leptin, and adiponectin in 29 obese children with NAFLD, 33 obese children without liver involvement, and 30 control children. The diagnosis and severity of NAFLD was based on ultrasound scan, after exclusion of infectious and metabolic disorders. Obese children with NAFLD had significantly increased carotid IMT [mean 0.58 (95% confidence intervals 0.54–0.62 mm)] than obese children without liver involvement [0.49 (0.46–0.52) mm; p = 0.001] and control children [0.40 (0.36–0.43) mm; p < 0.0005]. In a stepwise multiple regression model, after adjusting for age, gender, Tanner stage, and cardiovascular risk factors, the severity of fatty liver was significantly associated with maximum IMT (b = 0.08; p < 0.0005). Our results suggest that NAFLD is strongly associated with carotid atherosclerosis even in childhood.

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Nonalcoholic Fatty Liver Disease and Carotid Atherosclerosis in Children

Abstract Nonalcoholic fatty liver disease (NAFLD) is closely associated with several metabolic syndrome features, including obesity, dyslipidemia, insulin resistance, and increased cardiovascular risk. The present study was undertaken to assess whether NAFLD in children is associated with increased carotid artery intima-media thickness (IMT), a marker of early-generalized atherosclerosis. We analyzed carotid IMT along with serum triglycerides, total, low-density lipoprotein and high-density lipoprotein cholesterol, glucose, insulin, insulin resistance index (as homeostasis model assessment of insulin resistance), aminotransferases, leptin, and adiponectin in 29 obese children with NAFLD, 33 obese children without liver involvement, and 30 control children. The diagnosis and severity of NAFLD was based on ultrasound scan, after exclusion of infectious and metabolic disorders. Obese children with NAFLD had significantly increased carotid IMT [mean 0.58 (95% confidence intervals 0.54–0.62 mm)] than obese children without liver involvement [0.49 (0.46–0.52) mm; p = 0.001] and control children [0.40 (0.36–0.43) mm; p < 0.0005]. In a stepwise multiple regression model, after adjusting for age, gender, Tanner stage, and cardiovascular risk factors, the severity of fatty liver was significantly associated with maximum IMT (b = 0.08; p < 0.0005). Our results suggest that NAFLD is strongly associated with carotid atherosclerosis even in childhood. Main Nonalcoholic fatty liver disease (NAFLD) encompasses a range of liver histology severity and outcomes in the absence of chronic alcohol use (1–3). The mildest form is simple steatosis in which triglycerides accumulate within hepatocytes. A more advanced form of NAFLD, nonalcoholic steatohepatitis (NASH), includes inflammation and liver cell injury. The condition was originally described in diabetic, middle-aged women without a history of significant alcohol use with liver histology consistent with alcoholic hepatitis. NAFLD is strongly associated with obesity, type 2 diabetes, and dyslipidemia, and most patients have evidence of insulin resistance (2,3). Thus, NAFLD shares many features of the metabolic syndrome, a highly atherogenic condition, and its presence could signify a substantial cardiovascular risk above and beyond that conferred by individual risk factors. Although an association between hepatic steatosis and atherosclerotic risk factors has been described in adult patients (4–9), possible relationships between NAFLD and atherosclerosis in children remain to be investigated. Autoptic findings of an interesting study on the association between fatty liver and atherosclerosis in 817 children (age, 2–19 y) who died of external causes (accident, homicide, suicide) showed that fatty liver was present in 15% of the children. Mild atherosclerosis was present in 21% and moderate to severe atherosclerosis in 2%. Atherosclerosis was significantly (p < 0.0001) more common in children with fatty liver (30%) than those without fatty liver (19%) (Schwimmer JB et al., Fatty liver as a determinant of atherosclerosis. Abstract presented at the 56th Annual Meeting of the American Association for the Study of Liver Diseases, November 11–15, 2005, San Francisco, CA. Hepatology 2005; 42:610). Common carotid artery intima-media thickness (IMT) is a noninvasive marker of subclinical atherosclerotic changes and is a feasible, reliable, valid, and cost-effective method. Increased IMT is associated with cardiovascular disease (CVD) risk factors as well as the presence and severity of coronary atherosclerosis and CVD (10–14). The aims of our study were to determine the presence of subclinical atherosclerosis in obese children with and without NAFLD and to evaluate correlates of carotid IMT in children with NAFLD. Identification of such correlates would provide a better understanding of the pathogenesis of subclinical atherosclerosis in persons with NAFLD and might lead to preventative measures. MATERIALS AND METHODS Subjects. Between May 2006 and April 2007, children with primary obesity [body mass index (BMI) above the 95th percentile for age and gender] who had been referred to the Department of Pediatrics, La Sapienza University of Rome, Italy, for evaluation for fatty liver upon detection of hepatomegaly (defined as a liver edge greater than 2 cm below the right costal margin) and/or elevated liver chemistry (defined as serum alanine aminotransferase and/or aspartate aminotransferase levels 1.5 times above normal values for age) were recruited consecutively for study participation. In these subjects, causes of chronic hepatitis other than obesity, including hepatitis B, hepatitis C, alpha-1-antitrypsin deficiency, Wilson disease, autoimmune hepatitis, drug toxicity, and total parenteral nutrition were excluded. Children were excluded if they had type 1 or 2 diabetes, any condition known to influence body composition, insulin action, or insulin secretion (e.g., glucoc (...truncated)


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Lucia Pacifico, Vito Cantisani, Paolo Ricci, John F Osborn, Elisa Schiavo, Caterina Anania, Eva Ferrara, Giuliano Dvisic, Claudio Chiesa. Nonalcoholic Fatty Liver Disease and Carotid Atherosclerosis in Children, Pediatric Research, 2008, pp. 423-427, Issue: 63, DOI: 10.1203/PDR.0b013e318165b8e7