Presentation (CTI)

OBJECTIVES: Fibrolamellar hepatocellular carcinoma (FLC) is an ultra-rare primary liver malignancy affecting mainly adolescents and young adults without chronic liver disease. This targeted literature review synthesized published epidemiologic evidence on FLC incidence, demographic patterns, temporal trends, and prevalence evidence gaps to inform disease burden assessment, health technology assessment, and economic evaluations.
METHODS: A literature search was conducted in PubMed and Google Scholar to identify studies reporting epidemiologic outcomes in patients with FLC. Eligible studies included population-based registry analyses, retrospective cohort studies, and observational studies reporting incidence, prevalence, mortality, or survival. Data were extracted into evidence tables and synthesized narratively.
RESULTS: The search identified 1,173 records; 50 underwent full-text review, and 5 studies met inclusion criteria. All included studies used US population-based registries, primarily SEER. Age-adjusted incidence was consistently low, with most estimates near 0.02 per 100,000 population. One analysis estimated 602 annual US cases, equivalent to 0.185 per 100,000; regional incidence was 0.017 per 100,000. Some analyses suggested increasing incidence, including growth in FLC as a proportion of liver cancer cases from 1.9% in 2005 to 5.8% in 2020. FLC showed slight male predominance and a median diagnosis age of 27 years, with peaks among adolescents/young adults and older adults. Incidence was broadly similar across major racial and ethnic groups, although lower rates were reported among American Indian/Alaska Native populations. No prevalence estimates were identified.
CONCLUSIONS: FLC is an ultra-rare liver malignancy with very low incidence and limited epidemiologic evidence. Available data suggest diagnosis often occurs in younger patients, with possible temporal increases in reported incidence. Lack of robust population-based prevalence estimates remains a key evidence gap for burden estimation, economic modeling, and HTA. Further registry-based and multinational studies are needed to better characterize FLC epidemiology and support clinical and reimbursement decision-making.