Canberk ÇINAR, Ayşe Sena ÖZŞEN UYGUR, Yeliz TANRIVERDİ ÇAYCI, Demet GÜR VURAL, Kemal BİLGİN, Asuman BİRİNCİ
Journal of Experimental and Clinical Medicine - 2026;43(2):191-196
Although anti-HCV screening is widely used, the value of the antibody signal level (Cut-off Index, COI) in predicting the presence of active viremia remains controversial. This study aimed to evaluate the relationship between anti-HCV COI levels and HCV RNA positivity, and to investigate the potential value of low COI values in excluding viremia. A total of 312 patients with anti-HCV reactivity (COI >=1.0) and an available HCV RNA test result between January 2023 and June 2025 were evaluated retrospectively. When repeated results were recorded for the same patient, the first anti-HCV result and the first valid HCV RNA result were included in the analysis. Anti-HCV testing was performed by chemiluminescent immunoassay, and HCV RNA testing by PCR. The diagnostic performance of the anti-HCV COI value in predicting HCV RNA positivity was assessed using ROC analysis, the Youden index, sensitivity, specificity, positive predictive value, negative predictive value, and 95% confidence intervals. The association between COI groups and HCV RNA positivity was evaluated using the chi-square test and Fisher's exact test. HCV RNA positivity was detected in 42 (13.5%) of the 312 patients included. The discriminative power of the anti-HCV COI value as a continuous marker for HCV RNA positivity was poor (AUC: 0.438; 95% CI: 0.278-0.606). The relationship between HCV RNA positivity and COI level was not linear; positivity was highest in the 10.01-50.00 COI range (32.5%), with lower rates in the low and very high COI groups (p<0.001). The statistically derived threshold based on the Youden index was 16.46. At this threshold, sensitivity was 97.6% (95% CI: 87.7-99.6), specificity 28.5% (95% CI: 23.5-34.2), positive predictive value 17.5%, and negative predictive value 98.7%. No HCV RNA positivity was detected in the 54 patients with COI <5 (0%; 95% CI: 0-6.6). Whereas no HCV RNA positivity was observed in the COI <5 group, the HCV RNA positivity rate in the COI >=5 group was 16.3% (42/258); the difference between the two groups was statistically significant (Fisher's exact test, p<0.001). The anti-HCV COI level does not predict HCV RNA positivity in a linear manner, and its overall discriminative performance remains limited. The absence of HCV RNA positivity in the 54 patients with COI <5 (0%; 95% CI: 0-6.6) suggests that very low COI values may define a low-risk group for active viremia. However, the low AUC, low specificity, and low positive predictive value indicate that the COI level alone is insufficient to confirm active infection. Therefore, a COI <5 threshold may assist in prioritizing reflex molecular testing; however, it cannot replace HCV RNA testing, and HCV RNA testing is required to confirm active infection.
