S2365 Emerging Liver Epidemics: 25-Year Mortality Patterns of Non-Alcoholic Fatty Liver Disease (NAFLD) and Hepatocellular Carcinoma (HCC) in the United States

Introduction: Nonalcoholic Fatty Liver Disease (NAFLD), the hepatic manifestation of metabolic syndrome, is strongly associated with obesity, insulin resistance, and type 2 diabetes. It has become a leading cause of chronic liver disease in the U.S. and a major risk factor for Hepatocellular Carcinoma (HCC), even in non-cirrhotic patients. As both conditions rise in prevalence, understanding mortality trends is essential for public health planning. This study analyzes long-term mortality trends and demographic disparities related to NAFLD and HCC in the U.S. from 1999 to 2023. Methods: Mortality data were obtained from the CDC WONDER database using International Classification of Diseases, Tenth Revision (ICD-10) codes for NAFLD and HCC. Age-adjusted mortality rates (AAMRs) per 100,000 were calculated using the 2000 U.S. standard population. Joinpoint regression was used to estimate Annual Percent Change (APC) and Average Annual Percent Change (AAPC). Trends were assessed by sex, age, race/ethnicity, region, urban-rural status, and state. Significance was set at P < 0.05. Results: From 1999 to 2023, 57,862 deaths were attributed to NAFLD and HCC. Inpatient facilities accounted for 42% of deaths; 35.5% occurred at home. The overall AAMR doubled from 0.65 to 1.30 (AAPC: 2.8; 95% CI: 2.5–3.0; P < 0.000001). Men had 310% higher AAMRs than women (1.56 vs 0.38), although women had a steeper increase (AAPC: 3.6 vs 2.4; both P < 0.000001). Adults aged 55–74 had the highest AAMR (2.4), but those ≥75 experienced the sharpest rise (AAPC: 4.4; 95% CI: 4.0–5.1). Young adults (25–54) showed a decline (AAPC: -2.6; P < 0.00001). Hispanics had the highest AAMR (1.83), while non-Hispanic Whites had the fastest growth (AAPC: 3.2; P < 0.000001). The West had the highest regional AAMR (1.17), and the Midwest saw the steepest rise (AAPC: 3.7). Urban AAMRs were higher than rural (0.93 vs 0.74), though rural areas had faster increases (AAPC: 4.4 vs 2.6). States in the top 90th percentile included Texas, Oregon, Washington, Kentucky, and New Mexico. Conclusion: NAFLD and HCC mortality rates in the U.S. have more than doubled over 25 years, with marked disparities by sex, age, race, and geography. Rising trends in women, elderly adults, and rural populations highlight a shift in disease burden. The steep increases among non-Hispanic Whites and in the Midwest signal emerging hotspots requiring targeted prevention and early detection strategies.