Evaluation of Seven Rapid Diagnostic Tests for Detection of Hepatitis C Virus Antibodies in China

Bing Chen; Zhong-Hui Ma; Bing Xu; Hao Chang; Xiao-Xia He; Li-Jian Pei; Ya-Nan Ren; Wen-Ge Xing


J Viral Hepat. 2021;28(4):657-663. 

In This Article


To detect HCV infection, accurate and reliable diagnostic for HCV infection is indispensable. Currently, HCV RDT kits are widely used for screening tests of HCV infection, and it could reduce the risk of HCV transmission. Because HCV RDT kits are easy to perform without the need for expensive equipment or experienced personnel, and it has also high sensitivity and specificity.[5,11] In this study, we constructed HCV antibody basic panel, analytical specificity panel, mixed titre performance panel, characteristic panel, and commercially seroconversion panel, commercially genotype qualification panel to evaluate the performance of the HCV RDT kits. The basic panel results showed that the clinical sensitivity and clinical specificity of the seven HCV RDT kits ranged from 94% (95% CI: 83.2–98.6) to 100% (95% CI: 91.5–100), which was consistent with previous studies that the sensitivities of RDTs have varied from 90.8% to 99.9% and the specificities have varied from 92.1% to 99.9%.[12,13] The data suggest that HCV RDT kits evaluated in this study have high clinical sensitivity and clinical specificity to detect HCV infection.

In addition, the prevalence of HCV infection is different in different populations. For example, the prevalence of HCV infection in premarital screening population was 0.3%,[14] while that of intravenous drug user population was ranging from 22% to 95%.[15] Therefore, this study set the different prevalence of HCV infection in the population (0.5%, 1% and 10%, respectively), and combined with clinical sensitivity and specificity to calculate PPV and NPV. It was found that the NPVs of all HCV RDT kits in different HCV prevalence were more than 99.9%, indicating that the negative test results of RDT kits were truly uninfected. While the PPVs of most RDT kits were less than 50% when the prevalence of HCV infection was 0.5% and 1%, and the PPVs of all kits in HCV prevalence of 10% were ranging from 73.53% to 100%, suggesting that with increasing HCV prevalence, the proportion of HCV false-positive decreases, and when most HCV RDT kits were used in the population with low prevalence of HCV infection (such as voluntary blood donation),[16] this results may by false positive. Therefore, the results of the screening test that are reactive need to be further verified by supplementary tests.

Furthermore, early detection ability of RDT kit was also analysed by using HCV seroconversion panels.[5,12,17] It was found that the early detection time of A, E and G reagent was earlier than that of the reference assay, which indicated that the early detection ability of HCV RDT kit was roughly the same as that of ELISA. It was possible that the antigenic composition of RDT reagent coated was similar to that of ELISA, and even some antigen components of HCV RDT kits were superior to that of ELISA, resulting in more sensitive in early detection of antibodies compared to ELISA. However, the early detection ability of the other four HCV RDT reagents was lower than that of ELISA. Therefore, some HCV RDT kits should be further improved in kinds and composition of coated antigens in order to detect infected population as soon as possible.

And the genome of HCV has strong variability, HCV can be divided into 7 genotypes and 67 gene subtypes according to the variation sites.[18] In this study, HCV genotypes qualification panel containing HCV genotypes 1–6 were purchased to evaluate the detection ability of seven HCV RDT reagents for different genotypes. The results showed that the specimens with HCV genotypes 1b, 2a, 3a, 4a, 5a, 6 in genotype qualification panel could be detected, but specimens with genotypes 1a and 2b could not be detected. Moreover, previous data exhibited that the most common HCV genotype in China was genotype 1b, accounting for 56.8% of the total HCV infection, HCV genotype 1a was rare, accounting for only 1.4%, and HCV genotypes 4, 5, and 2b hadn't been found in mainland China.[1,19] Therefore, HCV RDT reagent can detect common HCV genotypes in China, but samples of domestically rare genotypes such as 1a and 2b may be missed.

Additionally, specimens with different S/CO in HCV mixed titre performance panel values and specimens with different bands in HCV characteristic panel were also tested by RDT kits. The results showed most HCV RDT kits had great performance in samples with different titres and different bands. But some low S/CO value specimens may be not fully detected by C, D, and F kit, and the single-band specimens with only NS4-1 bands could be missed by few HCV RDT kits, indicating that some HCV RDT kits had low sensitivity for diagnosing low-titre and/or single-band samples. This phenomenon may be due to the variability gene sequence of HCV NS4-1 region, resulting in weak antigen antibody reaction.[20] Therefore, specimens with low-titre and/or single-band may be not detected.

Our study has a few limitations in the study findings. Firstly, this study had low number of HCV-positive and -negative specimens in different serum panel. A larger specimen size from different populations would have given the study results more reliable and comprehensive. Secondly, some rare HCV genotypes could not be detected by HCV RDT reagents, but the number of samples with rare HCV genotypes was low, and these results were not verified.

In conclusion, all of seven HCV RDT kits evaluated had high clinical sensitivity, clinical specificity and analytical specificity, good anti-interference ability and good detection ability of early infection, which proved that they could meet the requirements of clinical HCV antibody screening. But some special samples (such as HCV subtype 1a and/or 2b, low titre, single band) may be missed by using certain HCV RDT kits.