Pediatric nonalcoholic fatty liver disease, metabolic syndrome and cardiovascular risk

Table 1 Published studies on the association between nonalcoholic fatty liver disease and markers of atherosclerosis in the pediatric population

Authors	Study population and sample size (No.)	Diagnosis	Outcomes	Main results
Schwimmer et al[49]	Children (817) who died of external causes (accident, homicide, suicide) from 1993 to 2003. Fatty liver was present in 15% of the children	Autoptic liver biopsy	Atherosclerosis was assessed as absent, mild (aorta only), moderate (coronary artery streaks/plaques), or severe (coronary artery narrowing)	For the entire cohort, mild atherosclerosis was present in 21% and moderate to severe atherosclerosis in 2%. Atherosclerosis was significantly more common in children with fatty liver than those without the disease (30% vs 19%; P < 0.001)
Schwimmer et al[32]	Overweight children with (150) and without (150) NAFLD matched for gender, age, and severity of obesity	Liver biopsy	Prevalence of cardiovascular risk factors (abdominal obesity, dyslipidemia, hypertension, insulin resistance, and glucose abnormalities)	NAFLD was strongly associated with multiple cardiovascular risk factors independently of both BMI and hyperinsulinemia
Pacifico et al[50]	Obese children with (29) and without (33) NAFLD; Healthy lean children (30)	Liver ultrasound	cIMT	cIMT was significantly higher in obese children with NAFLD compared with obese children without NAFLD and control group. Yet, the severity of fatty liver was associated with cIMT independently of anthropometric and metabolic features
Demircioglu et al[51]	Obese children with mild (32), moderate-severe (22) NAFLD, and without NAFLD (26); Healthy lean subjects (30) matched for age and gender	Liver ultrasound	cIMT	cIMT measured at left sites of common carotid artery, carotid bulb, and internal carotid artery was significantly higher in obese children compared with controls. Moreover, there was an increase in the mean cIMT of each segment with the increase in steatosis grade
Kelishadi et al[54]	Obese adolescents with (25) and without (25) components of MetS; Normal weight adolescents with (25) and without (25) components of MetS	Liver ultrasound and elevated ALT	cIMT	cIMT was significantly associated with insulin resistance and NAFLD
Manco et al[52]	Overweight and obese children with (31) and without (49) NAFLD matched for gender, age, and BMI	Liver biopsy	cIMT	cIMT was similar in cases and controls on the right side but significantly higher on the left site. There was no association between cIMT and severity of steatosis as well as fibrosis, and NAFLD activity score
Caserta et al[53]	Randomly selected adolescents (642) of whom 30.5% and 13.5% were, respectively, overweigth and obese. Overall prevalence of NAFLD, 12.5%	Liver ultrasound	cIMT	NAFLD, BMI (or waist circumference) and systolic blood pressure were independently associated with increased cIMT
		Liver biopsy	Atherogenic lipid profile (TG/HDL-c, TC/HDL-c, and LDL-c/HDL-c ratios)	The severity of liver injury was strongly associated with a more atherogenic lipid profile, independently of BMI, insulin resistance, and presence of MetS
Nobili et al[56]	Children with NAFLD (118)
Pacifico et al[47]	Obese children with (100) and without (150) NAFLD; Healthy lean children (150)	Liver ultrasound and elevated ALT	cIMT and FMD	Obese children had more functional and morphologic vascular changes than healthy lean controls, regardless of liver involvement. However, obese children with NAFLD had significantly decreased FMD response and increased cIMT compared to obese children without NAFLD independently of other cardiovascular risk factors and MetS
Weghuber et al[55]	Obese children with (14) and without (14) NAFLD	Proton MR spectroscopy	FMD	FMD was comparable between the two groups

NAFLD: Nonalcoholic fatty liver disease; BMI: Body mass index; cIMT: Carotid intima-media thickness; TG: Triglycerides; HDL-c: High-density lipoprotein cholesterol; TC: Total cholesterol; LDL-c: Low--density lipoprotein cholesterol; ALT: Alanine aminotransferase; FMD: Flow mediated dilation; MetS: Metabolic syndrome; MR: Magnetic resonance.