Ann Lab Med.  2018 Sep;38(5):466-472. 10.3343/alm.2018.38.5.466.

The Role of the Signal-to-Cutoff Ratio in Automated Anti-HCV Chemiluminescent Immunoassays by Referring to the Nucleic Acid Amplification Test and the Recombinant Immunoblot Assay

• Choi MS
• Lee K
• Hong YJ
• Song EY
• Kim DS
• Song J

• KMID: 2434737
• DOI: http://doi.org/10.3343/alm.2018.38.5.466

Abstract

BACKGROUND
Following discontinuation of the recombinant immunoblot assay (RIBA), the only available supplementary test for the detection of hepatitis C virus (HCV) is the nucleic acid amplification test (NAAT). However, the NAAT does not adequately detect past HCV. Consequently, it is hard to distinguish between past HCV infection and biological false positivity with an anti-HCV result alone. We assessed the diagnostic performance of two immunoassays: the ARCHITECT anti-HCV chemiluminescent microparticle immunoassay (CMIA; Abbott Diagnostics, Wiesbaden, Germany) and the Access HCV Ab PLUS chemiluminescent immunoassay (CIA; Bio-Rad, Marnes-la-Coquette, France). We also explored an optimized algorithm to determine the anti-HCV results.
METHODS
We tested 126,919 patients and 44,556 individuals who underwent a medical checkup. RIBA and NAAT were conducted for samples that tested anti-HCV-positive using CMIA and CIA. We assessed the optimal signal-to-cutoff (S/CO) ratio in HCV-positive samples.
RESULTS
In total, 1,035 blood samples tested anti-HCV-positive. Of these, RIBA was positive in 512, indeterminate in 160, and negative in 363 samples. One hundred sixty-five samples were NAAT-positive. Diagnostic sensitivity and positive predictive value (PPV) were 96.7% and 52.1%, respectively, for CMIA, and 94.7% and 72.3%, respectively, for CIA. The optimal S/CO ratio was 5.2 for CMIA and 2.6 for CIA at 95% PPV. In total, 286 samples tested positive in CMIA and 444 in CIA, while 443 samples tested positive in both assays.
CONCLUSIONS
It is hard to determine anti-HCV positivity based on the S/CO ratio alone. However, this study elucidated the role of the S/CO ratio by using the NAAT and RIBA.

Keyword

Hepatitis C virus; Chemiluminescent immunoassay; Recombinant immunoblot assay; Nucleic acid amplification test; Signal-to-cutoff ratio

MeSH Terms

Hepacivirus
Humans
Immunoassay*
Nucleic Acid Amplification Techniques*

Figure

• 

  Fig. 1 Results of the RIBA and NAAT with optimal S/CO associated with PPV of 95%: (A) CMIA, (B) CIA.Abbreviations: RIBA, recombinant immunoblot assay; P, positive; I, indeterminate; N, negative; NAAT, nucleic acid amplification test; S/CO, signal to cut-off ratio; PPV, positive predictive value; CMIA, chemiluminescent microparticle immunoassay; CIA, chemiluminescent immunoassay.

• 

  Fig. 2 Algorithm for screening anti-HCV with CMIA and CIA; groups A to F categorized by optimal values of each S/CO ratio: (A) CMIA to CIA, (B) CIA to CMIA.*Group B does not include Group A.Abbreviations: RIBA, recombinant immunoblot assay; P, positive; I, indeterminate; N, negative; NAAT, nucleic acid amplification test; S/CO, signal to cut-off ratio; PPV, positive predictive value; HCV, Hepatitis C virus; CMIA, chemiluminescent microparticle immunoassay; CIA, chemiluminescent immunoassay.

• 

  Fig. 3 Distribution of S/CO ratio according to the HCV infection states: (A) CMIA, (B) CIA. Bars represent the interquartile range, and the line within box represent the median. The I bars represent the 2.5th and 97.5th percentiles. Data are presented as mean standard deviation.Abbreviations: HCV, Hepatitis C virus; S/CO, signal to cut-off ratio; CMIA, chemiluminescent microparticle immunoassay; CIA, chemiluminescent immunoassay.

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