Ethnic and Sex Differences in the Association Between Metabolic Syndrome and Suspected Nonalcoholic Fatty Liver Disease in a Nationally Representative Sample of US Adolescents

Objectives: Nonalcoholic fatty liver disease (NAFLD) is increasingly recognized among overweight adolescents. Metabolic syndrome often coexists with NAFLD in adults. This study aimed to determine whether, in US adolescents, metabolic syndrome increases the odds of alanine aminotransferase (ALT) >40 U/L, a surrogate for NAFLD. Materials and Methods: A cross-sectional study of the association between metabolic syndrome and ALT>40 U/L was undertaken in a sample of 12- to 19-year-olds from the National Health and Nutrition Examination Survey, 1999 to 2002, representative of the US adolescent population. Subjects were excluded for incomplete data, pregnancy, steroid or hepatotoxic drug use, cholestasis or viral hepatitis, and alcohol intake. The metabolic syndrome was defined by adult criteria adapted for pediatric body size and blood pressure. The association of metabolic syndrome with ALT>40U/L, effect modifiers, and confounders were analyzed using National Health and Nutrition Examination Survey sampling weights. Results: Of 4902 adolescents, the 1323 included were similar to the excluded ones, except for the important variable sex (55% vs 49% male, P=0.03, respectively). The metabolic syndrome was associated with ALT>40U/L (odds ratio [OR] 16.7, confidence interval [CI] 6.2-45.1, P < 0.001) with significant interaction by sex: OR 20.4 (CI 6.2-66.7, P < 0.001) for males versus 3.1 (CI 0.4-25.1, P=0.3) for females. Further stratification of males suggested interaction by ethnicity: OR 5.0 (CI 1.3-19.0, P=0.02) for Hispanics versus 34.3 (CI 7.61-55.4, P < 0.001) for non-Hispanics. Among Hispanic males, adjustment for body mass index :, score explained the association (OR 0.6; CI 0.1-2.9, P=0.5), whereas among non-Hispanic males, the association remained after adjustment for BMIz (OR 11.1; CI 3.2-38.0, P<0.001). Conclusions: Metabolic syndrome is strongly associated with ALT>40U/L in US male adolescents. Body mass index z score explained this association among Hispanics, but not among non-Hispanic males. Significant sex and ethnic differences exist in the association of pediatric metabolic syndrome with elevated ALT. JPGN 49:442-449, 2009.