Utilization of Signal-to-Cutoff Ratio of Hepatitis C Virus Antibody Assay in Predicting HCV Viremia among Hemodialysis Patients

Abstract

Background: Hepatitis C virus (HCV) infection is a common cause of acute and chronic hepatitis among the hemodialysis population. To prevent cross infection between hemodialysis patients during the hemodialysis procedure, routine screening of anti-HCV antibody is recommended. However, a reactive anti-HCV EIA test is not equal to active HCV infection. An expensive RT-PCR study is required to confirm HCV viremia. This will significantly increase the cost burden because payment for each hemodialysis treatment is very low in Taiwan. Thus, it is useful to identify parameters that could predict HCV viremia among anti-HCV-reactive patients. In this study, we examined the usefulness of signal-to-cut (S/CO) ratio of anti-HCV antibody in discriminating HCV viremia from non-viremia among the anti-HCV-reactive hemodialysis population. Materials and Methods: In a cross-sectional measurement of anti-HCV antibody among 369 chronic hemodialysis patients, 44 showed reactive and 9 grey zone reaction for anti-HCV. These 53 patients underwent further blood tests for the measurement of AST, ALT and HCV RNA (by RT-PCR). The results of RT-PCR were used as a dependent variable. Then, S/CO ratios of anti-HCV, serum AST, ALT levels, age and duration of hemodialysis were used as independent variables to undergo ROC curve and logistic regression analysis. Results: Thirty-six of the 53 reactive and grey zone patients were positive for HCV RNA in the RT-PCR study. Patients who were positive for HCV RNA had a higher S/CO ratio (p < 0.01), higher AST and ALT levels (p < 0.01), and longer duration on hemodialysis (p < 0.05) than those negative for HCV RNA. Logistic regression revealed that only S/CO ratio was a significant predictor for HCV viremia (p = 0.004). ROC curve analysis showed that S/CO ratio had a highest area under curve (0.967, p < 0.001), followed by ALT (0.826, p < 0.001), AST (0.778, p = 0.001), duration on hemodialysis (0.606, p = 0.215) and age (0.426, p = 0.386) in discriminating HCV viremia from non-viremia. Using a cutoff S/CO ratio of 65, we can confirm HCV viremia with a diagnostic specificity of 100%, sensitivity of 80.1% and positive predictive value of 100%. Conclusion: S/CO ratio is a useful indicator in predicting HCV viremia among anti-HCV-reactive hemodialysis patients. Patients with an S/CO ratio >65 can be regarded as those with active HCV infection. Alternatively, patients with reactive anti-HCV but with an S/CO ratio <65 should receive further RT-PCR test.

Decreasing Hepatitis C Virus Infection in Thailand in the Past Decade: Evidence from the 2014 National Survey

“…The higher OD value from the S/CO ratio also correlated with the likelihood of an active HCV infection. In contrast, a lower S/CO ratio was predictive of HCV RNA negativity [ 22 ] as HCV RNA was only detected in 2 samples in the low S/CO-ratio group (7%). The latter may be due to several reasons including spontaneous clearance of previous HCV exposure, low viral load, or occult infection [ 23 – 24 ].…”

Determination of anti-HCV signal to cut-off value in patients with hepatitis C virus infection and the variety of antibody responses

“…Using a cutoff S/Co ratio of 24, they could confirm HCV viremia with a sensitivity and positive predictive value (PPV) of 91.7%, specificity and negative predictive value (NPV) of 82.4%. The sensitivity, specificity, PPV, and NPV were found to be 86.1%, 94.1%, 96.9%, 76.2% respectively when S/Co ratio was set 44 as cutoff [26].…”

“…Pan et al [25] used Elecsys Anti-HCV II (Roche Diagnostics) screening test and confirmed the results with RIBA and found the S/Co ratio as 12.27 with 97.8% sensitivity and 86% specificity. Kao et al [26] examined the S/Co ratio for AxSYM Microparticle Enzyme Immunoassay (MEIA) (Abbott Laboratories) using PCR for confirmation and found the S/Co ration optimal at 24 and 44. Using a cutoff S/Co ratio of 24, they could confirm HCV viremia with a sensitivity and positive predictive value (PPV) of 91.7%, specificity and negative predictive value (NPV) of 82.4%.…”

Prediction of HCV load using genotype, liver biomarkers, and clinical symptoms by a mathematical model in patients with HCV infection

“…Therefore, simpler, less expensive, and more rapid methods and/or algorithms are required for the quantification of HCV viremia . Recently, Kao et al used the signal‐to‐cut (S/CO) ratio of anti‐HCV antibody to predict HCV viremia, among a hemodialysis population. They demonstrated that a cut‐off S/CO ratio of >65 had 100% specificity, 80.1% sensitivity, and 100% positive predictive value for discriminating HCV viremia from non‐viremia.…”