Diagnostic accuracy of tests to detect hepatitis B surface antigen: a systematic review of the literature and meta-analysis

Abstract

BackgroundChronic Hepatitis B Virus (HBV) infection is characterised by the persistence of hepatitis B surface antigen (HBsAg). Expanding HBV diagnosis and treatment programmes into low resource settings will require high quality but inexpensive rapid diagnostic tests (RDTs) in addition to laboratory-based enzyme immunoassays (EIAs) to detect HBsAg. The purpose of this review is to assess the clinical accuracy of available diagnostic tests to detect HBsAg to inform recommendations on testing strategies in 2017 WHO hepatitis testing guidelines.MethodsThe systematic review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines using 9 databases. Two reviewers independently extracted data according to a pre-specified plan and evaluated study quality. Meta-analysis was performed. HBsAg diagnostic accuracy of rapid diagnostic tests (RDTs) was compared to enzyme immunoassay (EIA) and nucleic-acid test (NAT) reference standards. Subanalyses were performed to determine accuracy among brands, HIV-status and specimen type.ResultsOf the 40 studies that met the inclusion criteria, 33 compared RDTs and/or EIAs against EIAs and 7 against NATs as reference standards. Thirty studies assessed diagnostic accuracy of 33 brands of RDTs in 23,716 individuals from 23 countries using EIA as the reference standard. The pooled sensitivity and specificity were 90.0% (95% CI: 89.1, 90.8) and 99.5% (95% CI: 99.4, 99.5) respectively, but accuracy varied widely among brands. Accuracy did not differ significantly whether serum, plasma, venous or capillary whole blood was used. Pooled sensitivity of RDTs in 5 studies of HIV-positive persons was lower at 72.3% (95% CI: 67.9, 76.4) compared to that in HIV-negative persons, but specificity remained high. Five studies evaluated 8 EIAs against a chemiluminescence immunoassay reference standard with a pooled sensitivity and specificity of 88.9% (95% CI: 87.0, 90.6) and 98.4% (95% CI: 97.8, 98.8), respectively. Accuracy of both RDTs and EIAs using a NAT reference were generally lower, especially amongst HIV-positive cohorts.ConclusionsHBsAg RDTs have good sensitivity and excellent specificity compared to laboratory immunoassays as a reference standard. Sensitivity of HBsAg RDTs may be lower in HIV infected individuals.Electronic supplementary materialThe online version of this article (10.1186/s12879-017-2772-3) contains supplementary material, which is available to authorized users.

Molecular epidemiology of hepatitis B virus mutants associated with vaccine escape, drug resistance and diagnosis failure

“…The prevalence of DFMs, likewise VEMs, has been increasing since massive introduction of the vaccine . Therefore, there is growing public concern regarding assay sensitivity to HBsAg mutants in clinical diagnosis since selection of DFMs carry implicit risk of false‐negative results . In this regard, there is a concerted effort to understand how mutants affect “a” determinant antigenicity …”

“…52,53 Detection of HBsAg is crucial for HBV infection diagnosis and routinely used either for testing of individuals with suspected HBV infection or for screening in blood donors. 54 In the present study, DFMs were observed in 10.7% of the cases, and most of the mutations overlapped with previously described genotype. Twenty-two of the 28 mutation types observed in the analysed positions had demonstrated low ability to bind antibodies.…”

“…Detection of HBsAg is crucial for HBV infection diagnosis and routinely used either for testing of individuals with suspected HBV infection or for screening in blood donors …”

“…1.5%; HBV-F1b: 39.8%; and HBV-F4: 18.5%. The patient's age was evenly distributed among the different genotypes: HBV-A 45 (37)(38)(39)(40)(41)(42)(43)(44)(45)(46)(47)(48)(49)(50)(51)(52)(53)(54)(55)(56), HBV-D 44 and HBV-F 44 , P = 0.900.…”

Prevalence and burden of HBV co‐infection among people living with HIV: A global systematic review and meta‐analysis

“…We also did not exclude populations based on receiving ART, with few studies reporting the prevalence of ART making it difficult to adjust for the effects of treatment. The use of tenofovir‐based ART regimens may have reduced detection of HBsAg among some samples . Finally, we have not taken into account increases in both ART coverage and the use of tenofovir‐based ART regimens that may result in lower levels of co‐infection in later years.…”