Anti-HCV Signal-to-Cutoff Ratio in Predicting Hepatitis C Viremia

Hepatitis C virus (HCV) is one of the major etiologic agents of chronic liver diseases. Early and effective screening test of HCV was developed since the virus was first identified in 1989. The screening test of HCV is antiHCV antibody test by immunoassays and the infection status is confirmed by recombinant immunoblot assay (RIBA) and nucleic acid testing of HCV. Anti-HCV test was firstly developed by enzyme-linked immunosorbent assay which has relatively good sensitivity and specificity. Recently, it has been replaced by automated chemiluminescent immunoassay (CLIA) because of laboratory automation trend and advantages of its improved sensitivity and specificity. But, sometimes the screening immunoassays have been too much improved their sensitivities. Especially among populations with low (<10%) prevalence of HCV infection, assays for anti-HCV antibodies show high false-positive rates [1]. This is particularly problematic in asymptomatic persons with no clinical information available or in those who are being tested for the first time and in determining the need for postexposure follow-up. Therefore, positive results for HCV antibody screening tests require confirmation with other more specific supplementary tests such as RIBA or a nucleic acid test [2]. However, some laboratories lack an established laboratory standard for such supplemental testing or lack understanding of performance and interpretation of the screening and supplemental HCV tests. The high cost of the supplemental tests also makes them unavailable in many laboratories. One of the simple methods is sample Signal-to-Cutoff (S/CO) ratio of anti-HCV immunoassay. So the Center for Disease Control and Prevention (CDC) published guidelines that recommended supplemental tests to be based on anti-HCV assay S/CO ratios [2]. Generally, the S/CO value of more than 1 is regarded as positive in CLIA test. However, owing to improvement in the sensitivity of HCV tests, it is suggested that more accurate standard for reflecting positive HCV infection is needed. Thus, establishing optimal S/CO ratio is prerequisite for avoiding unnecessary further HCV tests which are currently adopted for increasing the reliability of diagnosis. In this regard, S/CO ratio is thought to better reflect HCV infection status of patients. However, significant value of S/CO ratio determining true infection status seems to be different from company to company. Thus, the difference in the ratio from reagents should be taken into account when judging HCV viremia. According to the CDC guideline, reflex supplemental testing may be limited to screening test-positive patients with average S/CO ratios <3.8, as anti-HCV positive samples with average S/CO ratios ≥3.8 would be highly predictive of the RIBA positivity (≥95%) [2]. Other studies have also evaluated the clinical significance of low S/CO ratios and found good correlation between S/CO ratio of anti-HCV and HCV viremia [3-8]. Some studies even suggested the elimination of reflex supplemental testing in samples with low S/CO ratio in order to save costs and reduce unnecessary testing [5,8]. These time and cost saving efforts have been reflected in another way in the study by Seo et al. They evaluated the utility of low S/CO ratio in predicting HCV viremia and in deciding whether to opt for qualitative or quantitative HCV RNA test in a HCV antibody positive patient. The authors suggest the use of qualitative HCV RNA testing in patients with antiHCV S/CO ratio <10.9 and quantitative HCV RNA testing in patients with anti-HCV ≥10.9. This is a novel approach to reduce time and cost of diagnosis, but unfortunately, DOI: 10.3904/kjim.2009.24.4.299 EDITORIAL