Age, comorbidity burden, and mortality risk in hospitalized patients with hepatocellular carcinoma

Hepatocellular carcinoma (HCC) is a cancer of older adults, yet the extent to which age versus comorbidity burden drives outcomes is underexplored. Understanding this distinction is critical to avoid both under-treatment and over-treatment in older adults with HCC. Adult patients with a diagnosis of HCC or cirrhosis were identified from the National Inpatient Sample, years 2016-2018. Age was categorized as <45, 45-64, 65-74, and ≥75 years. Comorbidity burden was assessed with the Hospital Frailty Risk Score (HFRS). Nested multivariable logistic regression models were used to examine the effect of comorbidity adjustment on the association between age and in-hospital mortality, stratifying by HCC status. Among 426,633 patients, 26,653 (6.2%) had HCC, and 5.9% died in the hospital. Comorbidity burden varied significantly by age, with HCC patients ≥65 years having a more than 2-fold increased prevalence of comorbidities such as coronary artery disease and heart failure ( p <0.001 for each). Among patients with HCC, age was associated with in-hospital mortality in unadjusted models (Age 45-64 y: OR=1.35; 95% CI: 1.02, 1.78; p =0.04; Age 65-74 y: OR=1.32, 95% CI: 1.00, 1.74; p =0.048). Adjustment for HFRS attenuated the association between age and in-hospital mortality such that it was no longer significant. In contrast, HFRS remained associated with mortality in fully adjusted models; each point increase in HFRS was associated with a 15% increased odds of in-hospital mortality (95% CI: 1.14, 1.16; p <0.001). Among a nationally representative cohort of hospitalized patients with HCC, comorbidity burden-not chronological age-was associated with in-hospital mortality. These findings highlight the importance of considering measures of physiologic reserve when engaging in treatment decision-making in patients with HCC, and moving beyond a focus on chronologic age as a predictor of outcomes.