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Background: Non-alcoholic fatty liver disease (NAFLD) is usually asymptomatic and lacks a specific biomarker; therefore, many individuals might remain undiagnosed even with advanced liver fibrosis. The aim of this study was to clarify the prevalence and clinical features of subjects with a high risk of advanced liver fibrosis in the general population, using the Fibrosis-4 (FIB-4) index., Methods: We retrospectively investigated 6,087 subjects without known liver disease who had participated in an annual health checkup examination. We analyzed the factors associated with high FIB-4 index (≥ 2.67) using a logistic regression analysis., Results: Among the 6,087 subjects, 76 (1.2%) had high FIB-4 index. Multivariate analysis identified hypertension (odds ratio [OR]; 9.040; 95% confidence interval [CI], 4.081-20.024; P < 0.001) and diabetes mellitus (OR = 4.251; 95% CI, 1.773-10.193; P = 0.001) as important risk factors for high FIB-4 index. The rates of hypertension and diabetes mellitus in subjects with high FIB-4 index were 78.9% and 23.7%, respectively. No significant association was observed between obesity or large waist circumference and high FIB-4 index. A history of cardiovascular disease was significantly more common in subjects with high FIB-4 index. These results were also observed in subjects with normal liver function test., Conclusions: The present study revealed that approximately 1% of the general Japanese population has a high risk of advanced liver fibrosis. Many of these patients had hypertension and/or diabetes mellitus. Our findings suggest that there are many undiagnosed patients NAFLD with risk of advanced liver fibrosis in the general population., (© 2022. The Author(s).)