Diagnostic accuracy of detection and quantification of HBV-DNA and HCV-RNA using dried blood spot (DBS) samples – a systematic review and meta-analysis

Abstract

BackgroundThe detection and quantification of hepatitis B (HBV) DNA and hepatitis C (HCV) RNA in whole blood collected on dried blood spots (DBS) may facilitate access to diagnosis and treatment of HBV and HCV infection in resource-poor settings. We evaluated the diagnostic performance of DBS compared to venous blood samples for detection and quantification of HBV-DNA and HCV-RNA in two systematic reviews and meta-analyses on the diagnostic accuracy of HBV DNA and HCV RNA from DBS compared to venous blood samples.MethodsWe searched MEDLINE, Embase, Global Health, Web of Science, LILAC and Cochrane library for studies that assessed diagnostic accuracy with DBS. Heterogeneity was assessed and where appropriate pooled estimates of sensitivity and specificity were generated using bivariate analyses with maximum likelihood estimates and 95% confidence intervals. We also conducted a narrative review on the impact of varying storage conditions or different cut-offs for detection from studies that undertook this in a subset of samples. The QUADAS-2 tool was used to assess risk of bias.ResultsIn the quantitative synthesis for diagnostic accuracy of HBV-DNA using DBS, 521 citations were identified, and 12 studies met the inclusion criteria. Overall quality of studies was rated as low. The pooled estimate of sensitivity and specificity for HBV-DNA was 95% (95% CI: 83–99) and 99% (95% CI: 53–100), respectively. In the two studies that reported on cut-offs and limit of detection (LoD) – one reported a sensitivity of 98% for a cut-off of ≥2000 IU/ml and another reported a LoD of 914 IU/ml using a commercial assay. Varying storage conditions for individual samples did not result in a significant variation of results. In the synthesis for diagnostic accuracy of HCV-RNA using DBS, 15 studies met the inclusion criteria, and this included six additional studies to a previously published review. The pooled sensitivity and specificity was 98% (95% CI:95–99) and 98% (95% CI:95–99.0), respectively. Varying storage conditions resulted in a decrease in accuracy for quantification but not for reported positivity.ConclusionsThese findings show a high level of diagnostic performance for the use of DBS for HBV-DNA and HCV-RNA detection. However, this was based on a limited number and quality of studies. There is a need for development of standardized protocols by manufacturers on the use of DBS with their assays, as well as for larger studies on use of DBS conducted in different settings and with varying storage conditions.

Hepatitis C Guidance 2019 Update: American Association for the Study of Liver Diseases–Infectious Diseases Society of America Recommendations for Testing, Managing, and Treating Hepatitis C Virus Infection

“…Collection of dried blood spots is an option for sequential HCV‐antibody and reflex HCV‐RNA testing. Dried blood spot collection can be accomplished with a fingerstick rather than venepuncture, and transport does not require an intact cold chain, making this an advantageous testing option in rural areas and among people for whom phlebotomy is a testing barrier . An FDA‐approved quantitative or qualitative HCV‐RNA assay with a detection level of ≤25 IU/mL should be used.…”

Dried Blood Spot Tests for the Diagnosis and Therapeutic Monitoring of HIV and Viral Hepatitis B and C

“…For HBV, sensitivities and specificities are estimated at 95% on average (D'Avolio et al, 2010), and the threshold for inactive hepatitis is easily reached in DBS (<2000 IU/mL, approximately equivalent to <10,000 DNA copies/mL). For HCV, mean sensitivities and specificities are also high and estimated >98% (Lange et al, 2017b), which can be explained by the paucity of low HCV viremia during the natural history of this infection. Confirmation of HCV viremia by testing HCV core antigen (HCVcAg) on DBS has also recently been reported in intravenous drug users living in Africa and Asia (Mohamed et al, 2017;Nguyen et al, 2018).…”

Existence of Hepatitis B Surface Protein Mutations and Other Variants: Demand for Hepatitis B Infection Control in Cambodia

“…This study used the DBS samples to detect not only the HBV sero-markers but also HBV DNA and consequently both partial and full length genome sequences, which is the critical tool for the advanced molecular epidemiology. According to recent systematic review and meta-analysis report, the pooled estimate of sensitivity and specificity for HBV-DNA using DBS was 95% (95% CI: 83-99) and 99% (95% CI: 53-100), respectively [14].…”

“…Therefore, a total of 4,541 DBS samples (2,518 children and 2023 mothers) were tested for HBsAg (LumipulseII® HBsAg, Fujirebio, Japan with reported sensitivity of 100% and specificity of 99.7% [13]) by chemiluminescent enzyme immunoassay (CLEIA) using Lumipulse G1200 (Fujirebio Inc, Japan) with cut-off value of 1.0. The reported sensitivity and specificity of HBV DNA using DBS was 95% (95% CI: 83-99) and 99% (95% CI: 53-100), respectively [14]. The vaccination history was taken from yellow book (the vaccination records) provided by Ministry of Health of Cambodia.…”