Nonalcoholic fatty liver disease and the heart in children and adolescents.

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.

Left ventricular dysfunction in obese children and adolescents with nonalcoholic fatty liver disease.

UNLABELLED: Nonalcoholic fatty liver disease (NAFLD) may increase the risk for cardiac dysfunction. The present study aimed to determine whether, in children, NAFLD is associated with subclinical left ventricular (LV) structural and functional abnormalities independently of metabolic risk factors. We performed a complete echocardiographic study including tissue Doppler imaging, magnetic resonance imaging (MRI) for measurement of hepatic fat fraction (HFF) and abdominal fat mass distribution, along with lipid profile, insulin sensitivity, and high-sensitivity C-reactive protein in 108 obese children, 54 with (HFF ≥5%) and 54 without NAFLD, and 18 lean healthy subjects. The three groups were matched for age, gender, and pubertal status, and obese children with NAFLD were matched for body mass index/standard deviation score with those without NAFLD. Forty-one of the children with NAFLD underwent liver biopsy. Compared to controls and children without liver involvement, those with NAFLD had features of LV diastolic dysfunction, including higher E-to-e' ratio and lower e' tissue velocity. The Tei index (reflecting the combined systolic and diastolic LV function) was also significantly higher in NAFLD children. Among children with biopsy-proven NAFLD, 26 had definite nonalcoholic steatohepatitis (NASH) and 15 were not-NASH. Patients with definite-NASH had significantly lower e' velocity and significantly higher E-to-e' and Tei index (P < 0.001, respectively) than those without NASH. In multiple logistic regression analysis, NAFLD was the only statistically significant variable associated with increased E-to-e' ratio, whereas NAFLD and systolic blood pressure were significantly associated with increased Tei index. CONCLUSION: Asymptomatic obese children with NAFLD exhibit features of early LV diastolic and systolic dysfunction, and these abnormalities are more severe in those with NASH.