Nonalcoholic fatty liver disease and the heart in children and adolescents

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: Atherosclerosis; Cardiac function; Cardiac structure; Children; Nonalcoholic fatty liver disease.

Figure 1

Suggested pathophysiological mechanisms linking nonalcoholic fatty liver disease to atherosclerosis and cardiac abnormalities in obese subjects. FFAs: Fatty free acids; CRP: C-reactive protein; IL-6: Interleukin-6; TNF-α: Tumor necrosis factor-α; FGF-21: Fibroblast growth factor-21; VLDL: Very low density lipoprotein; LDL-c: Low density lipoprotein cholesterol; HDL-c: High density lipoprotein cholesterol; NAFLD: Nonalcoholic fatty liver disease; NASH: Nonalcoholic steatohepatitis.

Figure 2

Histological and immunohistochemical features of nonalcoholic fatty liver disease. A: Hematoxylin-Eosin (HE) in nonalcoholic fatty liver disease (NAFLD) biopsy shows hepatic steatosis (fatty liver). Original Magnification: 10 ×; B: Immunohistochemistry for phosphorylated (p) nuclear factor κB shows the nuclear expression by hepatocytes in NAFLD (arrows). Original Magnification: 40 ×; C: Macrophages in NAFLD. Immunohistochemistry for CD68 shows the presence of macrophages in nonalcoholic steatohepatitis (yellow arrows). Original Magnification: 40 ×. Photos were obtained from a liver biopsy of a 60-year-old male affected by NAFLD. Photos are original and taken in Prof. Gaudio’s Laboratory.