Shifting etiologic burden of hepatocellular carcinoma hospitalizations in the United States, 2016–2022: A National Inpatient Sample analysis.

e16345 Background: The epidemiology of chronic liver disease is evolving with widespread use of direct-acting antivirals (DAAs) for hepatitis C virus (HCV) and rising prevalence of metabolic dysfunction and alcohol use. We evaluated national trends in diagnosis-code–based etiologic attribution among hospitalizations for hepatocellular carcinoma (HCC) in the United States. Methods: We conducted a repeated cross-sectional analysis of the National Inpatient Sample (2016–2022). Adult (≥18 years) hospitalizations with a principal diagnosis of HCC (ICD-10-CM C22.0) were identified. Etiologies were assigned using ICD-10-CM codes in any diagnosis field and categorized as HCV, hepatitis B virus (HBV), alcohol-associated liver disease (ALD), nonalcoholic fatty liver disease/nonalcoholic steatohepatitis (NAFLD/NASH), mixed (≥2 etiologies), or none/other (no listed etiology codes). Trends in etiology shares were assessed with survey-weighted logistic regression (odds ratio [OR] per year). Survey-weighted multivariable models evaluated associations between etiology and in-hospital mortality (adjusted OR [aOR]) and resource utilization (log[LOS+1], log[charges+1]), adjusting for demographics, payer, and hospital characteristics. Results: We identified 17,049 unweighted hospitalizations, representing an estimated 85,245 HCC hospitalizations nationally. Annual volume declined from 12,680 in 2016 (95% CI, 11,789–13,571) to 11,610 in 2022 (95% CI, 10,915–12,305). The proportion attributed to HCV decreased from 34.9% (95% CI, 32.9–37.0) to 19.5% (95% CI, 17.8–21.2; OR per year 0.88, 95% CI 0.86–0.89; p < 0.001). NAFLD/NASH increased from 5.0% to 8.8% (OR per year 1.11, 95% CI 1.08–1.14; p < 0.001) and ALD increased from 7.2% to 9.7% (OR per year 1.04, 95% CI 1.01–1.07; p = 0.003). None/other increased from 37.5% to 48.6%. Compared with HCV-related admissions, mixed etiology had higher in-hospital mortality (aOR 1.34, 95% CI 1.08–1.66) and none/other also had higher mortality (aOR 1.19, 95% CI 1.03–1.39), while NAFLD/NASH showed borderline lower mortality (aOR 0.74, 95% CI 0.54–1.00). NAFLD/NASH and mixed etiologies were associated with higher adjusted charges (ratios 1.21 and 1.11, respectively) and longer LOS (ratios 1.05 and 1.10, respectively) versus HCV. Conclusions: From 2016 to 2022, the inpatient burden of HCC shifted substantially from HCV toward metabolic and alcohol-associated etiologies, alongside a growing proportion of unclassified cases. These trends underscore the need for prevention and care strategies addressing metabolic and alcohol-related risk factors and for improved capture of liver disease etiology in administrative data.