Ten-Year Trends in Hepatocellular Carcinoma Mortality: Examining the Interaction Between Fibrosis Score and Patient Age.

Abstract

Background: Hepatocellular carcinoma (HCC) remains a major cause of cancer-related mortality worldwide, with survival outcomes influenced by a range of demographic and pathological factors. While cirrhosis is a well-established risk factor, recent evidence shows that HCC can also develop in patients with only mild to moderate liver fibrosis. However, there is limited understanding of how fibrosis severity interacts with other clinical variables, such as patient age, to affect mortality. This study aims to explore how fibrosis scores relate to both overall and cancer-specific mortality in US HCC patients, with an emphasis on how this relationship may shift across different age groups.

Methods: We utilized data from the Surveillance, Epidemiology, and End Results (SEER) database to identify 15,796 adult patients diagnosed with HCC between 2010 and 2021. Baseline demographics, disease characteristics, and treatment variables were examined. Mortality outcomes were evaluated using Cox proportional hazard regression. Variables significant at p < 0.1 in univariate analysis were included in multivariate models to identify independent predictors of mortality (with hazard ratios [HRs] > 1 signifying increased risk). A secondary analysis assessed how age modifies the association between fibrosis score and mortality.

Results: The study population was predominantly male (77.2%), with most patients aged 60-79 (59.6%) and presenting with localized disease (61%). A majority had advanced liver fibrosis or cirrhosis (81.7%) and lived in large urban areas (62.9%). Crude comparisons indicated that male sex, older age, single status, advanced tumor stage, lower income, and cirrhosis were linked to worse outcomes. In adjusted models, independent predictors of increased mortality included male sex, older age, unmarried status, and more advanced disease stage. Receipt of surgery or chemotherapy was associated with a lower risk of death. Notably, the influence of fibrosis on mortality was found to be greater in older patients than in their younger counterparts.

Conclusions: This analysis identifies key prognostic indicators in HCC and suggests that the relationship between fibrosis and survival is not uniform across age groups. These findings support the need for age-specific clinical management strategies and highlight the potential benefit of early detection and appropriate interventions, even in non-cirrhotic patients.