Mortality trends from hepatocellular carcinoma associated with non-alcoholic fatty liver disease in the United States, 1999–2020: An analysis of the CDC WONDER database.

e16217 Background: Hepatocellular carcinoma (HCC) is a leading cause of cancer-related deaths, with non-alcoholic fatty liver disease (NAFLD) emerging as a significant risk factor. The rising prevalence of NAFLD, linked to obesity and metabolic syndrome, has led to its progression to HCC. This study analyzes trends in HCC mortality related to NAFLD from 1999 to 2020 to assess the disease burden and guide interventions. Methods: HCC deaths linked to NAFLD in adults aged 25 and older were retrieved from the CDC WONDER database (1999–2020) using ICD-10 codes liver cancer and NAFLD. Crude mortality rates (CMRs) and Age-adjusted mortality rates (AAMRs) per 100,000 were calculated by age, gender, region and race, with 95% confidence intervals (CI) for precision. Temporal trends and annual percentage changes (APCs) were analyzed using Joinpoint regression. Results: From 2005 to 2020, deaths increased by 1423%, from 23 to 277 annually, with total deaths reaching 1,446 and CMR rising from 0.001 to 0.083 per 100,000. Individuals aged 75-84 years had the highest CMR of 0.13 per 100,000 with an [APC: 23.26%; 95% CI: 18.61–31.40, p < 0.01], followed by 65-74 years at 0.13 per 100,000 [APC: 5.56%; 95% CI: 12.69–20.28, p < 0.0)] and 55-64 years at 0.04 [APC: 9.01%; 95% CI: 5.29–14.16, p < 0.01]. Conversely, 85+ years group had a decline with CMR of 0.05 per 100,000 [APC: -6.33%; 95% CI: -6.33 to -6.33, p < 0.01]. In the 45-54 years age group, the CMR was 0.02 per 100,000 [APC: 20%; 95% CI: 18.61–23.40, p < 0.01]. 20% of total deaths of the 45-54 years group occured in 2020, highlighting a growing impact on younger populations linked to NAFLD-associated HCC. Males had a higher CMR (0.03, APC: 18.72%, p < 0.01) compared to females (0.02, APC: 21.29%, p < 0.01). For AAMR, males had a higher rate (0.0372, APC: 15.84%, p < 0.01) than females (0.0216, APC: 19.87%, p < 0.01). Geographically, CMRs were highest in the West (0.03, APC: 21.26%, p < 0.01), followed by the South (0.02, APC: 22.86%, p < 0.01), Midwest (0.02, APC: 15.00%, p < 0.01), and Northeast (0.01, APC: 16.21%, p < 0.01). AAMRs mirrored these trends, with the West again having the highest rate (0.0499, APC: 17.55%, p < 0.01), followed by the Midwest (0.0378, APC: 19.30%, p < 0.01), South (0.0300, APC: 20.02%, p < 0.01), and Northeast (0.0285, APC: 56.99%, p < 0.01). Racially, Whites had the highest CMR (0.03, APC: 19.87%, p < 0.01), followed by American Indians/Alaska Natives, Asians/Pacific Islanders, and Black/African Americans. Conclusions: The sharp rise in mortality and tripling of deaths between 2016 and 2020, highlights a growing public health concern. Public health strategies should focus on equitable screening, early detection, and culturally tailored interventions to address systemic barriers. Expanding healthcare access, raising awareness, and incorporating social determinants are key to reducing the burden of HCC due to NAFLD.