Rural-Urban Disparities in Hepatocellular Carcinoma Deaths Are Driven by Hepatitis C-Related Hepatocellular Carcinoma

Recent data suggest emerging rural-urban disparities in hepatocellular carcinoma (HCC) burden in the United States. We aimed to assess (i) trends in rural vs urban HCC-related mortality and (ii) differences in underlying chronic liver disease etiologies contributing to HCC-related deaths.

We used the National Vital Statistics System to examine crude and age-adjusted HCC death rates overall and by etiology for rural and urban residents from 2005 to 2023. Using the National Cancer Institute Joinpoint Trend Analysis Software, we identified statistically significant changes in annual percentage change (APC) in HCC mortality rates.

Examining mortality rates over time, average APC in HCC deaths was significantly higher in rural residents (crude average annual percentage change [AAPC] 4.64, 95% confidence interval [CI] 4.10, 5.34; age-adjusted AAPC 3.53, 95% CI 3.09, 4.07) compared with urban residents (crude AAPC 2.72, 95% CI 2.43, 3.01; age-adjusted AAPC 1.68, 95% CI 1.28, 2.13). Differences in HCC death rate changes were driven by a significantly greater recent decline in HCC cases from hepatitis C virus (HCV) in urban residents (crude APC -6.69, 95% CI -8.85, -5.30 from 2017 to 2023) compared with rural residents (crude APC -3.31, 95% CI -8.05, 0.73 from 2016 to 2023).

Annual increases in HCC deaths have been more pronounced in rural compared with urban populations. Deaths from HCV-related HCC have declined with a geographical disparity that favors urban populations, possibly driven by decreased access to HCV screening or availability of highly effective direct-acting antiviral therapies for rural residents. These findings underscore the need for targeted HCV screening and treatment strategies in rural populations in addition to ongoing strategies to combat alcohol use and metabolic diseases.