Impact of metabolic and lifestyle risk factors on hepatocellular carcinoma incidence and outcomes.

Abstract

524 Background: Hepatocellular carcinoma (HCC) arises from a spectrum of underlying liver conditions and metabolic risk factors, such as the broadly defined steatotic liver disease (SLD), liver fibrosis, diabetes mellitus type 2 (DM2), hypertension (HTN), hyperlipidemia, and metabolic syndrome (MetS). Defining the incidence of these risk factors among patients with HCC and how they impact survival, stage at presentation, and trajectory of the disease, remains essential to surveillance and management strategies. Methods: We analyzed 1,231 Renown Health patients with HCC, incorporating data from diagnostic categories. Non-parametric tests, logistic regression, Kaplan-Meier survival estimates, and Cox proportional hazard models were used to assess associations between metabolic risk factors and survival, staging, and time from risk factor diagnosis to HCC onset. Demographic prognosticators of metabolic comorbidities and disparities in disease progression were also evaluated. Results: Across the cohort, the prevalence of metabolic comorbidities was substantial, with 380 patients with MetS (30.9%), 445 patients with DM2 (36.1%), and 809 patients with HTN (65.7%). Five-year survival estimates varied by risk factor, with the highest mortality observed among patients with alcoholism (5-year survival: 39.9%, 95% CI 35.3-45.0%). Demographically, patients with metabolic risk factors tended to be older and more frequently male. Hispanics were more likely to have DM2 (OR 2.13, 95% CI 1.46-3.12), and males more likely to have HTN (OR 1.37, 95% CI 1.06-1.77). Among 164 patients with cancer staging, no significant association was observed between DM2 and stage at HCC diagnosis (p = 0.31). Among 103 patients with accessible cancer staging and cholesterol measurements, cholesterol levels at diagnosis did not differ by stage (p = 0.53). Among 136 patients with diagnosed SLD, median time to HCC diagnosis was highly variable; however, no demographic disparities in time to progression were identified. Patients with MetS demonstrated heterogeneous timelines from first meeting criteria to HCC diagnosis, with some identified only after HCC was established. Limited sample sizes precluded direct comparisons of staging outcomes for SLD and fibrosis. Conclusions: Metabolic comorbidities, including MetS, DM2, HTN, and hyperlipidemia, are highly prevalent among patients with HCC. While certain risk factors, such as alcoholism, confer markedly worse survival, others like DM2 and cholesterol levels were not associated with stage at presentation. The variability in timelines from metabolic disease and SLD to the onset of HCC diagnosis underscores the heterogeneity of disease progression and highlights the need for tailored surveillance strategies. However, due to our small sample size, larger studies are warranted to clarify staging associations and to better define at-risk subgroups for earlier intervention.