Background: Nonalcoholic fatty liver disease (NAFLD) is thought to be the main driver for the recent rise of chronic liver disease and liver cancer. NAFLD is also associated with other obesity-related metabolic diseases. Relative fat deposition in the liver varies by race/ethnicity and may partially account for liver cancer disparities. Thus, we aimed to compare liver fat content across five racial/ethnic groups, assess their contribution to the metabolic syndrome (MetSx), and predict NAFLD using common blood biomarkers.
Methods: We conducted a cross-sectional study within the Multiethnic Cohort. A total of 1,861 healthy men and women aged 60-77 years were recruited, after stratification on sex, ethnicity (African, Japanese, Latino, Native Hawaiian, or white ancestry), and six BMI categories (range, 17.1-49.8 kg/m2). We estimated total fat mass using DXA and liver fat content using abdominal MR imaging. Fasting blood was analyzed for ~50 markers including adipocytokines, insulin and IGFs, lipids and lipid-soluble micronutrients, liver enzymes, and steroid hormones, using multiple assay platforms. Liver fat amounts were compared across sex and ethnic groups after adjustment for age, total fat mass, and height. The contribution of liver fat to MetSx was estimated in multivariable-adjusted mediation analysis. A prediction model for NAFLD was developed using regularized logistic regression.
Results: The correlation between liver fat and total fat was only moderate (rSp = 0.34) and varied across ethnic groups (0.20-0.55). Liver fat content was similar between the sexes but differed by ethnicity (p<.0001), with a four-fold range in NAFLD prevalence between Japanese Americans (57% in men, 72% in women) and African Americans (12%, 19%) after adjustment for total fat mass. Total fat-adjusted prevalence of MetSx also differed by ethnicity: compared to whites, it was higher among Japanese Americans and Native Hawaiian women and lower among African Americans and Latinos. This ethnic difference was significantly mediated by liver fat among African Americans (proportion mediated =19-24%), Japanese Americans (22-34%), and Native Hawaiian women (20%). The final prediction model for NAFLD included age, sex, BMI, waist circumference, waist/hip, and top five biomarker predictors (IGFBP2, HOMA-IR, TG, adiponectin, SHBG). Discrimination of NAFLD cases in a validation dataset had high accuracy (AUC=0.90), across ethnic groups (AUCs of 0.80-0.96), and was significantly improved by the biomarkers (p's for contrast<.0001, except in African Americans).
Conclusions: Relative fat storage in the liver varies substantially by race/ethnicity. In particular, Japanese Americans and Native Hawaiian women appear to experience a greater metabolic burden from their propensity to store excess fat in ectopic areas, which is consistent with a stronger association of BMI with liver cancer in these groups. Key metabolism markers may be used to successfully detect and monitor NAFLD patients of in various ethnic groups.
Citation Format: Unhee Lim, Lynne R. Wilkens, Kristine R. Monroe, Iona Cheng, Bruce S. Kristal, Johanna W. Lampe, Meredith A. Hullar, John Shepherd, Thomas Ernst, Loic Le Marchand. Racial/ethnic differences in liver fat, an obesity-associated risk factor for liver cancer [abstract]. In: Proceedings of the Eleventh AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2018 Nov 2-5; New Orleans, LA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(6 Suppl):Abstract nr IA38.