Pre-treatment host and viral factors may affect serum ferritin levels in patients with hepatitis C virus (HCV) infection. We delineated pre-treatment factors associated with hyperferritinemia in these patients. 1682 eligible patients underwent pre-treatment assessment for serum ferritin and various host/viral factors. Univariate and multivariate logistic regression analyses were conducted to evaluate factors associated with hyperferritinemia. Multivariate logistic regression analyses revealed that age > 50 years (adjusted odds ratio [OR]: 1.38 (95% confidence interval [CI] 1.09–1.74), p = 0.008), fibrosis stage ≥ F3 (adjusted OR: 1.36 (95% CI 1.04–1.77), p = 0.02), fibrosis index based on four parameters (FIB-4) > 3.25 (adjusted OR: 1.46 (95% CI 1.11–1.92), p = 0.01), presence of metabolic dysfunction-associated steatotic liver disease (MASLD) (adjusted OR: 1.43 (95% CI 1.21–1.76), p = 0.001), and alanine transaminase (ALT) > 2 folds upper limit of normal (ULN) (adjusted OR: 2.87 (95% CI 2.20–3.75), p < 0.001) were associated hyperferritinemia. The log
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value of HBV or HCV viral load was not associated with the log
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value of ferritin level (Spearman’s rank correlation coefficient: − 0.025, p = 0.81 and 0.002, p = 0.92). In conclusion, host factors, rather than viral factors, are associated with hyperferritinemia in patients with HCV.