Nonalcoholic fatty liver disease (NAFLD) is now thought to be the most common liver disease worldwide. Cardiovascular complications are a leading cause of mortality in NAFLD. Fructose, a common nutrient in the westernized diet, has been reported to be associated with increased cardiovascular risk, but its impact on adolescents with NAFLD is not well understood. We designed a 4-week randomized, controlled, double-blinded beverage intervention study. Twenty-four overweight Hispanic-American adolescents who had hepatic fat >8% on imaging and who were regular consumers of sweet beverages were enrolled and randomized to calorie-matched study-provided fructose only or glucose only beverages. After 4 weeks, there was no significant change in hepatic fat or body weight in either group. In the glucose beverage group there was significantly improved adipose insulin sensitivity, high sensitivity C-reactive protein (hs-CRP), and low-density lipoprotein (LDL) oxidation. These findings demonstrate that reduction of fructose improves several important factors related to cardiovascular disease despite a lack of measurable improvement in hepatic steatosis. Reducing dietary fructose may be an effective intervention to blunt atherosclerosis progression among NAFLD patients and should be evaluated in longer term clinical trials.

Nonalcoholic fatty liver disease (NAFLD) has emerged as the major pediatric chronic liver disease, and it is estimated to affect more than one third of obese children in the U.S. Cardiovascular complications are a leading cause of increased mortality in adults with NAFLD and many adolescents with NAFLD already manifest signs of subclinical atherosclerosis including increased carotid intima-media thickness. Volume of intrahepatic fat was assessed in 50 Hispanic-American, overweight adolescents, using Magnetic Resonance Spectroscopy. Lipoprotein compositions were measured using Nuclear Magnetic Resonance. Plasma triglycerides (TG) (p = 0.003), TG/HDL ratio (p = 0.006), TG/apoB ratio (p = 0.011), large VLDL concentration (p = 0.019), VLDL particle size (p = 0.012), as well as small dense LDL concentration (p = 0.026) progressively increased across higher levels of hepatic fat severity, while large HDL concentration progressively declined (p = 0.043). This pattern of associations remained even after controlling for gender, BMI, visceral fat, and insulin resistance. Our findings suggest that increased hepatic fat is strongly associated with peripheral dyslipidemia and the amount of fat in the liver may influence cardiovascular risk. Further studies are needed to longitudinally monitor dyslipidemia in children with NAFLD and to examine whether the reduction of hepatic fat would attenuate their long-term CVD risk.

Summary: Background: Plasminogen activator inhibitor‐1 (PAI‐1) is the primary inhibitor of the endogenous fibrinolytic system and is known to be increased in obesity, insulin resistance and non‐alcoholic fatty liver disease (NAFLD). We previously demonstrated that PAI‐1 levels were closely related to the amount of hepatic steatosis in children.Objectives: The aim of this study was to characterize plasma PAI‐1 in relationship to severity of inflammation and fibrosis, as well as to plasma lipids in children with NAFLD.Methods: In 44 children with NAFLD, plasma PAI‐1 levels and lipids were measured at the time of a liver biopsy. Hepatic histological features were systematically scored. Trend analysis was applied to determine the correlation of plasma PAI‐1 levels with lipid markers for cardiovascular disease and with the staging of histological features in the liver.Results: We found that plasma PAI‐1 levels were significantly increased in children with increased severity of steatosis, lobular inflammation, ballooning and fibrosis. Furthermore, PAI‐1 was strongly correlated with plasma lipids and insulin resistance indices.Conclusions: PAI‐1 appears to be tightly related to both histologic severity of NAFLD as well as systemic features of the disease including insulin resistance and dyslipidemia. PAI‐1 may be a mediator of disease progression and future cardiovascular complications in children with NAFLD.