Determination of initial HBsAg cutoff index threshold for reporting HBsAg reactivity

Piya  Wongchampa; Arkom  Chaiwongkot; Rangsima  Reantragoon

Authors

Piya Wongchampa King Chulalongkorn Memorial Hospital, Thai Red Cross Society, Bangkok, Thailand
Arkom Chaiwongkot Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand
Rangsima Reantragoon Center of Excellence in Immunology and Immune-mediated Diseases, Faculty of Medicine, Chulalongkorn University, Bangkok,Thailand

Keywords:

Confirmatory neutralization test, cutoff index (COI), Hepatitis B surface antigen (HBsAg) screening, Hepatitis B virus (HBV) diagnosis

Abstract

Background: Commercially-available screening test for Hepatitis B surface antigen (HBsAg) are suggested as are suggested as confirmatory tests in all reactive, cases; however, report the results will take a long time, which increases the total test cost.

Objectives: To investigate the correlation between the cutoff index (COI) values of the initial HBsAg screening test and their corresponding confirmatory neutralization results to identify a COI value for distinguishing samples that truly need confirmatory neutralization tests.

Methods: This retrospective study analyzed 72,496 HBsAg screening test results using the Elecsys HBsAg II kit of patients between October 2019 and March 2022. Elecsys HBsAg II neutralization tests were performed on samples with COI values ranging from 0.9 to 30.0. The correlation between the (COI) value (0.9 - 30.0) and the percentage of neutralization confirmatory (tests HBsAg confirmed negative and positive groups) was plotted. The receiver operating characteristic (ROC) was also assessed.

Results: Of the 72,496 test results, 337 samples with COI $gif.latex?\leq$ 30.0 underwent confirmatory tests, yielding 313 positive samples. The ROC analysis revealed that the area under the curve was 0.9429 (P < 0.0001, 95% CI 0.8691 - 1) and the COI value of 3.5 had an excellent diagnostic value with the greatest positive likelihood ratio, providing 94.4% specificity (95% CI 74.2 - 99.7) and 88.3% sensitivity (95% CI 60.8 - 94.2). However, a high false positive rate (11.7%) was found in samples with COI values of 0.9 - 4.0, whereas samples with values between > 4.00 and 13.00 had a 3.9% false positive rate. On the contary, a COI value of 13.0 had 100.0% specificity.

Conclusion: In diagnostics, a COI value of $gif.latex?\geq$ 4.0 may be more practical in areas with limited resources for confirmatory tests. If the reasons for an increase in specificity outweigh the cost of confirmatory tests, a COI value of 13.0 is more appropriate. Each diagnostic laboratory may choose the COI value that suits their settings for practical diagnostic application in areas with limited resources for confirmatory tests.

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