Clinically Actionable Hypercholesterolemia and Hypertriglyceridemia in Children with Nonalcoholic Fatty Liver Disease.

OBJECTIVE: To determine the percentage of children with nonalcoholic fatty liver disease (NAFLD) in whom intervention for low-density lipoprotein cholesterol or triglycerides was indicated based on National Heart, Lung, and Blood Institute guidelines. STUDY DESIGN: This multicenter, longitudinal cohort study included children with NAFLD enrolled in the National Institute of Diabetes and Digestive and Kidney Diseases Nonalcoholic Steatohepatitis Clinical Research Network. Fasting lipid profiles were obtained at diagnosis. Standardized dietary recommendations were provided. After 1 year, lipid profiles were repeated and interpreted according to National Heart, Lung, and Blood Institute Expert Panel on Integrated Guidelines for Cardiovascular Health and Risk Reduction. Main outcomes were meeting criteria for clinically actionable dyslipidemia at baseline, and either achieving lipid goal at follow-up or meeting criteria for ongoing intervention. RESULTS: There were 585 participants, with a mean age of 12.8 years. The prevalence of children warranting intervention for low-density lipoprotein cholesterol at baseline was 14%. After 1 year of recommended dietary changes, 51% achieved goal low-density lipoprotein cholesterol, 27% qualified for enhanced dietary and lifestyle modifications, and 22% met criteria for pharmacologic intervention. Elevated triglycerides were more prevalent, with 51% meeting criteria for intervention. At 1 year, 25% achieved goal triglycerides with diet and lifestyle changes, 38% met criteria for advanced dietary modifications, and 37% qualified for antihyperlipidemic medications. CONCLUSIONS: More than one-half of children with NAFLD met intervention thresholds for dyslipidemia. Based on the burden of clinically relevant dyslipidemia, lipid screening in children with NAFLD is warranted. Clinicians caring for children with NAFLD should be familiar with lipid management.

Low and High Birth Weights Are Risk Factors for Nonalcoholic Fatty Liver Disease in Children.

OBJECTIVES: To examine the distribution of birth weight in children with nonalcoholic fatty liver disease (NAFLD) compared with the general US population, and to investigate the relationship between birth weight and severity of NAFLD. STUDY DESIGN: A multicenter, cross-sectional study of children with biopsy-proven NAFLD enrolled in the Nonalcoholic Steatohepatitis Clinical Research Network Database. Birth weight was categorized as low birth weight (LBW), normal birth weight (NBW), or high birth weight (HBW) and compared with the birth weight distribution in the general US population. The severity of liver histology was assessed by birth weight category. RESULTS: Children with NAFLD (n = 538) had overrepresentation of both LBW and HBW compared with the general US population (LBW, 9.3%; NBW, 75.8%; HBW, 14.9% vs LBW, 6.1%; NBW, 83.5%; HBW 10.5%; P < .0001). Children with HBW had significantly greater odds of having more severe steatosis (OR, 1.82, 95% CI. 1.15-2.88) and nonalcoholic steatohepatitis (OR, 2.03; 95% CI, 1.21-3.40) compared with children with NBW. In addition, children with NAFLD and LBW had significantly greater odds of having advanced fibrosis (OR, 2.23; 95% CI, 1.08-4.62). CONCLUSION: Birth weight involves maternal and in utero factors that may have long-lasting consequences. Children with both LBW and HBW may be at increased risk for developing NAFLD. Among children with NAFLD, those with LBW or HBW appear to be at increased risk for more severe disease.

Obesity, insulin resistance, and other clinicopathological correlates of pediatric nonalcoholic fatty liver disease.

OBJECTIVE: To describe the clinical characteristics of nonalcoholic fatty liver disease (NAFLD) in children, including insulin resistance, and to test for correlation with liver pathology. STUDY DESIGN: A retrospective review of children with biopsy-proven NAFLD at Children's Hospital San Diego from 1999 to 2002. Liver biopsy specimens were independently reviewed by two pathologists. RESULTS: Children with NAFLD (n=43) were mostly male (70%), Hispanic American (53%) and obese (88%). The criteria for insulin resistance were met by 95% of subjects. Steatosis was predicted by the combination of quantitative insulin sensitivity check index, age, and ethnicity (P<.0001). Portal inflammation was predicted by the combination of ALT and fasting insulin (P=.0009). Perisinusoidal fibrosis was predicted by the combination of AST, fasting insulin, and BMI Z score (P<.0001). Portal fibrosis was predicted by the combination of right upper quadrant pain and homeostasis model assessment of insulin resistance (P=.0028). CONCLUSIONS: We identified significant predictors of liver pathology in children with NAFLD. Children being evaluated for NAFLD should be screened for insulin resistance, which is nearly universal and correlates with liver histology.