Accuracy of Rapid Point-of-Care Diagnostic Tests for Hepatitis B Surface Antigen—A Systematic Review and Meta-analysis

doi:10.1016/j.jceh.2014.07.008

Journal of Clinical and Experimental Hepatology

Volume 4, Issue 3, September 2014, Pages 226-240

https://doi.org/10.1016/j.jceh.2014.07.008 Get rights and content

Background

Rapid point-of-care tests provide plausible diagnostic strategy for hepatitis B surface antigen (HBsAg) in low resource areas. However, their utility depends upon their overall performance. Our objective was to meta-analyze the diagnostic accuracy of rapid point-of-care tests for HBsAg.

Methods

Literature search was done with the help of a metasearch engine Mettā, a query interface for retrieving articles from five leading medical databases. Studies that employed rapid point-of-care tests for detection of HBsAg and compared the results with reference test were included. Two reviewers performed quality assessment of the studies and extracted data for estimating test accuracy. Twenty-seven studies were meta-analyzed and stratified by multiple parameters.

Results

Twenty-seven studies had evaluated 49 test brands and generated 76 data points. Sensitivity of individual tests varied widely and were heterogeneous (range 43.5%–99.8%); while specificity estimates were more robust and close to 100% (range 90%–100%). Overall pooled sensitivity, specificity, positive likelihood ratio (LR), negative LR and diagnostic odds ratio for all tests were 97.1% (95% CI, 96.1%–97.9%), 99.9% (CI, 99.8%–100%), 118.4 (CI, 84.7–165.5), 0.032 (CI, 0.023–0.045) and 4094.7 (CI, 2504.1–6600.8) respectively. This suggested high pooled accuracy for all studies. We found substantial heterogeneity between studies. Three factors (study location, reference standard and study score) appeared most strongly associated with test estimates and observed heterogeneity. The Determine test showed consistency in performance in studies done across developed and developing countries and the Determine and the BinaxNOW tests had significantly higher estimates than pooled estimates of remaining tests. Tests revealed analytical sensitivity of 4 IU/ml against manufacturer's claim of 0.5 IU/ml; reduced sensitivity with HBsAg mutants and poor performance in seroconversion panels.

Conclusions

Tests with better analytical sensitivity need to be developed and their feasibility and outcomes in various clinical settings need to be addressed.

Section snippets

Protocol

We sought to conduct a systematic review and meta-analysis on studies which evaluated accuracy of RPOCTs for HBsAg. A protocol was written that specified several aspects of the meta-analysis (available at our website www.drkhuroo.com; Appendix Document 1) as per PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-analysis) guidelines.²⁰ Two independent reviewers made literature search, performed quality assessment of the included studies and extracted data for estimating test

Literature Search

We identified 29 articles eligible for inclusion (Figure 1).11, 12, 13, 15, 16, 17, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51 Data from 2 studies had duplicate publications. Official report of International Consortium for Blood Safety 2007 (ICBS,¹²) was published as a full-text paper in a peer-reviewed journal.⁴⁷ Sera from another study were collected and tested in Malawi⁴⁴ and had shown conflicting results. The same sera were retested in UK and

Discussion

The present meta-analysis had six strengths when compared to 2 earlier studies10, 52: i) global and complete literature search, with strict inclusion criteria, ii) defined strategy to include and analyze inconclusive results, iii) use of Bivariate statistical model, iv) statistical comparison in meta-regression model of summary estimates of diagnostic accuracy within subgroups to make relevant conclusions, v) evaluation of heterogeneity and its potential sources in the meta-regression model,

Conclusions

RPOCTs have major benefits to offer in screening and control of HBV infection especially in far flung low resource endemic zones of the world. The tests are cheap, give rapid diagnosis, are convenient and easy to store, need small blood samples for testing, need minimal training of professionals for testing and need no or minimal expensive equipment. However, their global uptake needs to be addressed keeping in view the overall performance of the tests. With present low level of test accuracy

Funding source

Our study was funded by the “Dr. Khuroo's Medical Trust”, a non-profit organization to promote research and help poor patients for medical treatment. The funding source had no role in the conception, design or conduct of this review.

Conflicts of interest

All authors have none to declare.

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La hepatitis viral aparece más frecuentemente al nacer o durante la infancia y es una enfermedad cuyas vías de transmisión incluyen lágrimas, bilis, fluidos sexuales, sudor, leche, orina, heces y saliva. El objetivo del presente estudio fue analizar la especificidad de la inmunocromatografía y la prueba ELISA para el antígeno de superficie de hepatitis B y compararlas con la prueba PCR.
La muestra estuvo compuesta por 140 hombres y 60 mujeres referidos al hospital de la Escuela de Medicina de la Universidad de Urmia para diagnóstico de VHB por medio de prueba PCR. La prueba ELISA fue realizada con el kit de la Pioneer Medicine Company (Teherán, Irán).
Los resultados de la prueba rápida HBsAg y de la prueba ELISA fueron comparados con la prueba de PCR. La prueba rápida de HBsAg tuvo una sensibilidad del 97% y especificidad del 91%, mientras que la prueba ELISA tuvo una sensibilidad del 78% y especificidad del 76%.
De acuerdo con nuestros resultados, la prueba de inmunocromatografía fue precisa para diagnosticar HBsAg en sangre y la prueba ELISA tuvo sensibilidad y especificidad aceptables en comparación con la prueba de PCR.
Viral hepatitis, which appears most frequently at birth or during childhood, is a disease whose transmission routes include tears, bile, sexual fluids, sweat, milk, urine, feces, and saliva. The aim of the present study was to analyze the specificity of the immunochromatographic and ELISA diagnostic tests for hepatitis B surface antigen and compare them with PCR testing.
The study sample was made up of 140 men and 60 women referred to the Urmia Medical University hospital to undergo PCR testing for HBV diagnosis. The ELISA test was performed using the Pioneer Medicine Company kit (Tehran, Iran).
The results of the HBs-Ag rapid test and the ELISA test were compared with the PCR test. The HBs-Ag rapid test had 97% sensitivity and 91% specificity, whereas the ELISA test had 78% sensitivity and 76% specificity.
According to our results, the immunochromatographic test was accurate for diagnosing HBs-Ag in blood and the ELISA test had acceptable sensitivity and specificity, compared with PCR testing.
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Citation Excerpt :
It has a marginal cost increase of $8·55 per test compared with the two-test strategy (appendix p 7), yet it provides a comprehensive HBV serological profile, facilitating disease staging and linkage-to-care. While the rapid point-of-care test remains a cost-effective choice compared with the status quo, the extended dominance (ie, higher incremental cost-effectiveness ratio compared with other effective strategies) means it is a less preferable option, due to its suboptimal sensitivity and the need for confirmatory testing.21 Notably, the youngest age group (18–30 years) would benefit most from screening because identifying younger people who need vaccination would result in greater QALYs gained.
China has the highest prevalence of hepatitis B virus (HBV) infection worldwide. Universal HBV screening might enable China to reach the WHO 2030 target of 90% diagnostics, 80% treatment, and 65% HBV-related death reduction, and eventually elimination of viral hepatitis. We evaluated the cost-effectiveness of implementing universal HBV screening in China and identified optimal screening strategies.
We used a Markov cohort model, inputting parameters based on data from previous studies and public databases, to assess the cost-effectiveness of four HBV serological screening strategies in China in different screening scenarios. We simulated universal screening scenarios in 15 adult age groups between 18 and 70 years, with different years of screening implementation (2021, 2026, and 2031) and compared to the status quo (ie, no universal screening); in total, we investigated 180 different screening scenarios. We calculated the incremental cost-effectiveness ratio (ICER) between the different screening strategies and the status quo (current screening strategy). We performed probabilistic and one-way deterministic sensitivity analyses to assess the robustness of our findings.
With a willingness-to-pay level of three times the Chinese gross domestic product (GDP) per capita (US$30 828), all universal screening scenarios in 2021 were cost-effective compared with the status quo. The serum HBsAg/HBsAb/HBeAg/HBeAb/HBcAb (five-test) screening strategy in people aged 18–70 years was the most cost-effective strategy in 2021 (ICER $18 295/quality-adjusted life-years [QALY] gained). This strategy remained the most cost-effective, when the willingness-to-pay threshold was reduced to 2 times GDP per capita. The two-test strategy for people aged 18–70 years became more cost-effective at lower willingness-to-pay levels. The five-test strategy could prevent 3·46 million liver-related deaths in China over the lifetime of the cohort. It remained the most cost-effective strategy when implementation was delayed until 2026 (ICER $20 183/QALY) and 2031 (ICER $23 123/QALY). Screening young people (18–30 years) will no longer be cost-effective in delayed scenarios.
The five-test universal screening strategy in people aged 18–70 years, implemented within the next 10 years, is the optimal HBV screening strategy for China. Other screening strategies could be cost-effective alternatives, if budget is limited in rural areas. Delaying strategy implementation reduces overall cost-effectiveness. Early screening initiation will aid global efforts in achieving viral hepatitis elimination.
National Natural Science Foundation of China.
Performance of rapid diagnostic tests for the detection of anti-HBs in various patient populations
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Citation Excerpt :
Most of these assays meet the WHO-recommended analytical sensitivity of 0.13 international units (IU)/L or 4 IU/L, depending on the targeted population [3]. However, in recent evaluations, the analytical sensitivity of individual RDTs varied widely, while the specificity of most of them appeared to be satisfactory [4,5]. RDTs for anti-HBs detection are currently used in some parts of the world and only one has received product license in Europe, but not in the US.
Rapid diagnostic tests (RDTs) represent an attractive alternative method to conventional diagnosis of hepatitis B virus (HBV) infection.
The aim of the present study was to evaluate the diagnostic performance of commercially available RDTs for the detection of anti-HBs in various patient populations.
A total of 347 individuals, 198 positive and 149 negative for anti-HBs, were studied.
The specificity of RDT detection of anti-HBs in serum was 98.0%, 96.0% and 97.3% with TOYO® HBsAb Test, QuickProfile™ HBsAb test and QuickProfile™ HBV-3 Panel test, respectively. The diagnostic sensitivity varied between 60.4% and 69.5%. The sensitivity of the three RDTs was markedly better when testing serum samples with an anti-HBs titer higher than 100 IU/L, and reached 90% or more for an anti-HBs titer above 150 IU/L.
This performance was disappointing because the assays were not sensitive enough to detect low antibody titers. Thus, these tests require further improvement before they can be widely used in clinical practice.
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El diagnóstico serológico de las infecciones en fase aguda implica la detección de la respuesta IgM específica, marcador eficaz de infección primaria, aunque con menos validez en las reactivaciones o reinfecciones. El objetivo de este artículo es proporcionar una visión actualizada del diagnóstico rápido en serología mediante la detección del isotipo IgM y revisar sus aplicaciones y limitaciones. Se analizan especialmente ensayos Point-of-Care (PoC) utilizados en áreas geográficas donde las pruebas tradicionales son inaccesibles, y en otras circunstancias donde su empleo acerca el diagnóstico a la población diana, debido a que pueden efectuarse en centros no sanitarios. Asimismo, su empleo disminuye el tiempo transcurrido entre la toma de muestra y el diagnóstico, facilitando al clínico la toma de decisiones. Los ensayos PoC han probado su coste-efectividad, especialmente en la prevención de la transmisión vertical de la sífilis y en la infección por el VIH.
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View all citing articles on Scopus

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Review ArticleAccuracy of Rapid Point-of-Care Diagnostic Tests for Hepatitis B Surface Antigen—A Systematic Review and Meta-analysis

Background

Methods

Results

Conclusions

Section snippets

Protocol

Literature Search

Discussion

Conclusions

Funding source

Conflicts of interest

Hepatitis B virus infection

N Engl J Med

Epidemiology and prevention of hepatitis B

Semin Liver Dis

The laboratory diagnosis of hepatitis B virus

Can J Infect Dis Med Microbiol

Hepatitis B surface antigen (HBsAg) assays—are they good enough for their current uses?

Clin Chem

Advances in the molecular diagnosis of hepatitis B infection: providing insight into the next generation of disease

Semin Liver Dis

Economic evidence and point-of-care testing

Clin Biochem Rev

Update: HIV Counseling and Testing Using Rapid Tests—United States

Rapid and simple point of care diagnostics for STIs (Editorial)

Sex Transm Infect

Rapid point-of-care first-line screening tests for hepatitis B infection: a meta-analysis of diagnostic accuracy (1980-2010)

Am J Gastroenterol

Evaluation of the performance of two rapid immuno chromatographic tests for detection of hepatitis B surface antigen and anti HCV antibodies using ELISA tested samples

AKEMU

Diagnostic accuracy studies: how to report and analyse inconclusive test results

BMJ

Evaluation of immunochromatographic assay systems for rapid detection of hepatitis B surface antigen and antibody, Dainascreen HBsAg and Dainascreen Ausab

J Clin Microbiol

Evaluation of a new rapid test for the combined detection of hepatitis B virus surface antigen and hepatitis B virus e antigen

J Clin Microbiol

Evaluation of a new hepatitis B virus surface antigen rapid test with improved sensitivity

J Clin Microbiol

Quantifying heterogeneity in a meta-analysis

Stat Med

Quantification of HBsAg in serum: characteristics of the assays

OA Hepatol

Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement

PLoS Med

Treatment with proton pump inhibitors in acute non-variceal upper gastrointestinal bleeding: a meta-analysis

J Gastroenterol Hepatol

Design and implementation of metta, a metasearch engine for biomedical literature retrieval intended for systematic reviewers

Health Inf Sci Syst

QUADAS-2: a revised tool for the quality assessment of diagnostic accuracy studies

Ann Intern Med

Toward complete and accurate reporting of studies of diagnostic accuracy: the STARD initiative

Ann Intern Med

Bivariate analysis of sensitivity and specificity produces informative summary measures in diagnostic reviews

J Clin Epidemiol

Meta-analysis in clinical trials

Control Clin Trials

Applications of meta-analysis in pathology practice

Am J Clin Pathol

Review Article
Accuracy of Rapid Point-of-Care Diagnostic Tests for Hepatitis B Surface Antigen—A Systematic Review and Meta-analysis