Background: Non-alcoholic fatty liver disease (NAFLD) is a growing global health burden, strongly linked to metabolic disorders and cardiovascular disease (CVD). While the Fibrosis-4 (FIB-4) index is a validated non-invasive tool for assessing liver fibrosis risk, its relationship with lipid profiles, particularly non-high-density lipoprotein cholesterol (non-HDL-C), remains understudied. This research aimed to evaluate the prevalence of NAFLD-related fibrosis risk and its association with non-HDL-C among working-age adults in Iran, emphasizing implications for early metabolic and cardiovascular risk stratification.
Methods: A cross-sectional study analyzed 4,817 employed individuals (aged 35–65 years) undergoing routine occupational health exams in Isfahan, Iran (2023–2024). Participants with viral hepatitis or inherited liver diseases were excluded. FIB-4 scores were calculated using age, AST, ALT, and platelet counts, categorizing fibrosis risk as low (≤1.30), moderate (1.30–2.67), or high (>2.67). Non-HDL-C was derived from total cholesterol minus HDL-C, stratified into five clinical categories.
Findings: The study population was mainly male (91%), with a mean BMI of 26.5 kg/m². Most participants exhibited low FIB-4-derived fibrosis risk (92.3%), while 7.5% and 0.2% had moderate and high risk, respectively. Non-HDL-C levels showed a weak inverse correlation with FIB-4 scores (r = -0.091, p < 0.001), with higher non-HDL-C categories linked to reduced fibrosis risk (p = 0.007). For instance, 46.5% of moderate/high-risk individuals had non-HDL-C <130 mg/dL versus 36.5% in the low-risk group. Age and male sex were independently associated with elevated fibrosis risk (p < 0.001). Despite statistical significance, the clinical significance of the inverse lipid-fibrosis relationship is still unclear and requires further study.
Conclusion: This study highlights the utility of FIB-4 as a non-invasive tool for identifying NAFLD-related fibrosis risk in occupational populations. The paradoxical inverse association between non-HDL-C and fibrosis stages underscores the complexity of lipid metabolism in NAFLD pathogenesis. Integrating FIB-4 and lipid profiling may improve the early detection of metabolic and cardiovascular complications.