Trends in mortality from unspecified malignant neoplasm of the liver among U.S. adults aged ≥45 years, 1999–2023.

Abstract

e16196 Background: Unspecified malignant neoplasm of the liver (ICD-10: C22.9) represents a diagnostic category encompassing liver cancers that lack detailed histologic or anatomic classification. Although this category may reflect limitations in diagnostic testing, reporting, or documentation, it has substantial implications for the accuracy of cancer surveillance and mortality trend interpretation. Over the past two decades, advances in diagnostic imaging, pathology, and coding practices have improved cancer classification, yet a considerable proportion of liver cancer deaths continue to be recorded as “unspecified.” Such cases may obscure the true epidemiologic patterns of hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC), complicating national and regional assessments of disease burden. Moreover, mortality patterns related to unspecified malignancies may reveal underlying inequities. Thus, this study evaluates long-term trends in mortality attributed to unspecified malignant neoplasm of the liver among U.S. adults aged ≥45 years from 1999 through 2023, stratified by sex, age, race and ethnicity, geographic region, and level of urbanization. Methods: We analyzed CDC WONDER underlying cause-of-death data, identifying deaths coded as C22.9. Age-adjusted mortality rates (AAMRs) per 100,000 population were calculated, and Joinpoint regression was used to estimate average annual percent change (AAPC) with 95% confidence intervals (CIs). Results: A total of 198,299 deaths were recorded from 1999–2023. The overall AAMR decreased slightly but in a statistically insignificant manner from 5.4 to 5.2 (AAPC:-0.02%, 95% CI: -0.49 to 0.45). Males had lower decrease in mortality than females (AAPC: -0.082% vs. -0.21%, P-value: 0.75 vs. 0.68). Non-Hispanic (NH) Asian or Pacific Islander individuals showed the largest decrease (AAPC: -2.57%), while NH Black (AAPC: -0.85%) and Hispanic populations (AAPC: -0.51%) maintained elevated AAMRs. Regionally, the South had the highest mortality burden (n = 88,703; AAPC: 0.32%, P-value: 0.46). Adults aged 65–85+ had the greatest mortality increase (AAPC: 0.34%), while those aged 45–64 showed declines (AAPC: -0.9%, P-value: < 0.01). Non-metropolitan areas had greater mortality increase than metropolitan areas (AAPC: 0.58% vs. 0.51%). Conclusions: Despite marked progress in liver cancer diagnostics and classification, mortality associated with unspecified malignant neoplasm of the liver has remained largely stable in the United States over the past quarter century. However, addressing these disparities through enhanced diagnostic precision, standardized reporting, and targeted public health interventions could improve understanding of true liver cancer epidemiology and guide equitable resource allocation for prevention, detection, and treatment across demographic and geographic subgroups.