Results: Among 145 patients with serologically silent occult HCV infection 45 (31%) tested anti-HCVcore-positive at the time of the diagnostic biopsy. Anti-HCVcore was detected in 143/145 (98.6%) chronic hepatitis C patients but in none of the 140 patients with HCV-unrelated liver disease (P< 0.001). A serological follow-up was conducted in occult HCV-infected patients (every 3−6 months for at least 12 months). Among 23 anti-HCVcorepositive patients at baseline, 18 remained antibody-reactive on all occasions tested; anti-HCVcore fluctuated in 4 (from positive to negative and viceversa) and was lost in one patient. Similarly, among 31 anti-HCVcorenegative at baseline, 17 remained antibody non-reactive; however, 4 patients seroconverted to anti-HCVcore and remained so whereas antiHCVcore became reactive in 10 patients on at least one occasion. Thus, a total of 59/145 (40.7%) patients with occult HCV infection reacted in the anti-HCVcore assay at any time-point analyzed, including 14 initially non-reactive patients. By supplemental anti-HCV immunoblot assay 16/83 (19.2%) sera reacted weakly with a single core-peptide band (indeterminate test result) of which 10/16 (62.5%) reacted in the anti-HCVcore ELISA. According to anti-HCVcore status, occult HCV-infected patients who tested anti-HCVcore-positive showed significantly greater scores of necroinflammation (P = 0.046) and percentages of HCVRNA-positive hepatocytes (P = 0.004) compared with the anti-HCVcore-negative counterparts. Conclusion: Anti-HCVcore is detectable in 40% patients with serologically silent occult HCV infection. Anti-HCVcore testing improves serodiagnosis of HCV infection in patients lacking serum anti-HCV and HCVRNA using commercial tests. This anti-HCVcore assay may be useful in tracking subclinical HCV infections.