Systemic and healthcare burden of elevated Fibrosis-4 in the general population: a nationwide matched-cohort analysis
Year: 2026
Type: article
Study design: Observational Study
Abstract: INTRODUCTION: The Fibrosis‑4 (FIB‑4) index, a widely used noninvasive marker of hepatic fibrosis, shows prognostic value beyond hepatology, yet its broader systemic and health care implications remain unclear. OBJECTIVES: We aimed to characterize the systemic disease burden, health care utilization, and long‑term outcomes linked to elevated FIB‑4 score. PATIENTS AND METHODS: We conducted a large‑scale, matched-cohort study using real‑world data from a nationally representative health care provider. Adults aged 40-80 years with available laboratory data were included, comprising 21 540 individuals with FIB‑4 equal to or above 2.67, matched 1:1 to 21 540 controls with FIB‑4 below 1.45 by age, sex, socioeconomic status, and ethnicity. Cross‑sectional and longitudinal analyses assessed clinical characteristics, health care utilization, and long‑term outcomes over median (interquartile range) follow‑up of 6.2 (4.9-7.8) years. RESULTS: The individuals with elevated FIB‑4 exhibited substantially higher baseline rates of cardiovascular disease, autoimmune disorders, and malignancies. Elevated FIB‑4 was associated with greater pharmacologic exposure and higher utilization of multidisciplinary, diagnostic, procedural, and hospital‑based services. Over the follow‑up period, the individuals with FIB‑4 equal to or above 2.67 experienced consistently greater cumulative incidence of systemic diseases and doubled all‑cause mortality (20.2% vs 9.7%; P <0.001). Annual health care expenditures were more than 3‑fold higher in the high-FIB‑4 group, driven by hospitalizations, specialist care, and procedural intensity. CONCLUSIONS: FIB‑4 equal to or above 2.67 robustly identifies individuals with disproportionate systemic morbidity, elevated mortality risk, and substantial health care resource utilization. Beyond staging hepatic fibrosis, FIB‑4 may function as a low‑cost marker of multimorbidity and health care complexity. Its incorporation into multidisciplinary risk stratification frameworks may enable earlier detection of high‑risk patients, inform preventive strategies, and support proactive population health management.
DOI: 10.20452/pamw.17225
Language: English
Subfield: Epidemiology
Field: Medicine
Domain: Health Sciences
Open Access status: diamond
OpenAlex ID: W7128798494
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