| Summary: | A large community cohort of adults who participated in a health screening program from 2003 to 2013 were prospectively analyzed for the risk factors of non-B, non-C (NBNC) hepatocellular carcinoma (HCC). The serostatus of hepatitis B and C of 52,642 participants was linked to the mortality and cancer registration data of the Health and Welfare Data Science Center, Ministry of Health and Welfare, Taiwan. During a median follow-up of 6 years, 35 of the 43,545 participants who were negative for both HBsAg and anti-HCV antibody developed HCC. Multivariate Cox regression analysis revealed that old age (hazard ratio, 95% CI: 1.058, 1.019–1.098, <i>p</i> = 0.003); male sex (2.446, 1.200–4.985, <i>p</i> = 0.014); high aspartate aminotransferase levels (6.816, 2.945–15.779, <i>p</i> < 0.001); fibrosis index based on four factor score (1.262, 1.154–1.381, <i>p</i> < 0.001); blood sugar (1.009, 1.002–1.015, <i>p</i> = 0.006); and alpha-fetoprotein ≥15 ng/mL (143.938, 43.094–480.760, <i>p</i> < 0.001) were independent risk factors for HCC. By contrast, triglyceride >150 mg/dL was associated with a decreased risk of HCC (0.216, 0.074–0.625, <i>p</i> = 0.005). This prospective community-based study provided insights into the potential HCC risk factors which may shed some light in HCC prevention and screening.
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