Nonalcoholic fatty liver disease (NAFLD) leading to nonalcoholic steatohepatitis (NASH) is a major cause of chronic liver disease that may progress to cirrhosis and hepatocellular carcinoma (HCC). Considering the prevalence, particularly among Hispanics, understanding the etiology and mechanisms of this disease by race/ethnicity is imperative. We have established a multidisciplinary team to comprehensively characterize the dynamic interplay of multiple factors (genetics, lifestyle, environmental and immune factors) in NAFLD/NASH and the underlying mechanisms driving incidence, severity and progression that result in health disparities in Hispanics. We will identify factors associated with NAFLD development and progression in Hispanics and non- Hispanic whites (NHW) in Los Angeles County (LAC). The large immigrant populations in LAC offer unique perspectives and opportunities to examine health disparities in Hispanics. We will enroll 2,000 patients (1,000 Hispanics and 1,000 NHW) with FibroScan-confirmed advanced (>F2) and mild (?F1) hepatic fibrosis and 1,000 matched controls without ultrasonographic evidence of NAFLD recruited from the LAC and USC Keck Hospitals. We will collect biological specimens, clinical and detailed questionnaire data for sociodemographic and risk factors and use geospatial approaches to ascertain social and neighborhood-related factors. Case groups will be followed prospectively for disease progression.
Our specific aims are 1) to determine the contribution of lifestyle, clinical, social/environmental factors and genetics (nuclear and mitochondrial) to ethnic disparities in NAFLD risk, disease severity (advanced/mild fibrosis) in Hispanics and NHW; 2) to examine how differential gene expression revealed by scRNA-transcriptomic profiling of circulating innate immune cells in NAFLD varies according to polygenic risk scores and dietary factors; utilize bioinformatics approach to identify plasma proteins with diagnostic and predictive accuracy for NAFLD severity and progression; 3) to identify high-risk groups for NAFLD risk and progression by integrating genetics, lifestyle, clinical, social and contextual factors in Hispanics and NHW using an innovative latent variable analysis. Our study will culminate in novel, comprehensive, and innovative characterization of multi-level factors associated with phenotypic spectrum of NAFLD and disease progression and contribute significantly to the understanding of the etiology and mechanisms that influence disparities in NAFLD in high-risk Hispanic population.
Non-alcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease in modern society. NAFLD is predicted to become the leading indication for liver transplantation and is a risk factor for the development of hepatocellular carcinoma that can develop even without cirrhosis. In a large Hispanic and non- Hispanic White population with unequivocally staged levels of fibrosis, we will combine state-of-the-art approaches (e.g., lifestyle and environmental factors, unbiased genetic variation analyses, single-cell transcriptomic analyses of peripheral innate immune cells resulting in identification of diagnostic protein biomarkers, and structural integrated analyses) to gain novel mechanistic insights into NAFLD disparities in Hispanics and disease progression to fibrosis which is the single most important predictor of outcome.