PREVALENCE AND PREDICTORS OF NONALCOHOLIC FATTY LIVER DISEASE (NAFLD) IN VETERANS

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The objective of this application is to determine the burden of non-alcoholic fatty liver disease (NAFLD) among patients receiving primary care at the Department of Veterans Affairs (VA) health care system. NAFLD affects an estimated 20%-30% of the adult non-VA US population and is projected to become the main cause of end- stage liver disease in the next 10 years. NAFLD encompasses a histologic spectrum ranging from simple steatosis to non-alcoholic steatohepatitis (NASH). Around 20% of patients with NASH undergo fibrotic progression to cirrhosis, which increases risk of liver failure the risk of hepatocellular carcinoma. NAFLD is considered the hepatic complication of obesity and insulin resistance. Proper diagnosis of NAFLD and subsequent treatment (e.g., dietitian services) is associated with improved biochemical and histological features of NAFLD. There are also ongoing clinical trials with promising medications (e.g., obeticholic acid) for NASH. Given the veteran population is disproportionately affected by the main risk factors for NAFLD (e.g., diabetes, obesity), our central hypothesis is that the veteran population in primary care is particularly susceptible to a high burden from NAFLD. It is unclear whether the VA is currently equipped to deal with this costly disorder given the lack of basic information on the prevalence, determinants, and clinical recognition of NAFLD in the VA. Advances in magnetic resonance imaging (MRI) has revolutionized the diagnosis and severity staging of NAFLD, thus obviating the need for liver biopsy in most cases. However, the use of MRI for NAFLD screening in a primary care setting is impractical and expensive. There are no agreed upon clinical prediction rules, and none that is tested in VA settings. We will address our hypothesis by conducting a probability-based cross-sectional study of 1000 veterans (500 males and 500 females) enrolled in the VA for their primary healthcare. Specific Aim #1: To determine the overall and race- and sex- specific prevalence of NAFLD (and Advanced Hepatic Fibrosis) using highly sensitive and specific MRI criteria in a large and representative sample of veterans enrolled at the Michael E. DeBakey VA Medical Center in Houston for their primary healthcare. This aim will be accomplished by combined use of liver magnetic resonance imaging proton density fat fraction (MRI-PDFF) and elastography (MRE). Specific Aim #2: To evaluate the association between presence and severity of NAFLD and potential risk factors, including demographic (gender, race/ethnicity), anthropometric (BMI, waist circumference, and body fat by bioimpedance analysis), clinical (medical history, family history, and medications), serologic (CD18), genetic (PNPLA3), biochemical (LFTs, serologic biomarkers of hepatic fibrosis and steatosis), metabolic (serologic markers of metabolic syndrome), and lifestyle (smoking, alcohol, exercise) factors. Specific Aim #3: Use the information on risk factors and biomarkers to construct and validate an algorithm that can be used at the primary care level to identify patients at high risk of NAFLD and NASH for further referral. The information on prevalence in different groups are essential for effective VA healthcare planning and resource allocation. The study will aid in the clinical recognition of NAFLD in the VA primary care setting using VA specific risk factors. Finally, our study will provide data needed to support future research to develop clinical pathways for detection and referral.