Diagnostic accuracy of serological diagnosis of hepatitis C and B using dried blood spot samples (DBS): two systematic reviews and meta-analyses

Abstract

BackgroundDried blood spots (DBS) are a convenient tool to enable diagnostic testing for viral diseases due to transport, handling and logistical advantages over conventional venous blood sampling. A better understanding of the performance of serological testing for hepatitis C (HCV) and hepatitis B virus (HBV) from DBS is important to enable more widespread use of this sampling approach in resource limited settings, and to inform the 2017 World Health Organization (WHO) guidance on testing for HBV/HCV.MethodsWe conducted two systematic reviews and meta-analyses on the diagnostic accuracy of HCV antibody (HCV-Ab) and HBV surface antigen (HBsAg) from DBS samples compared to venous blood samples. MEDLINE, EMBASE, Global Health and Cochrane library were searched for studies that assessed diagnostic accuracy with DBS and agreement between DBS and venous sampling. Heterogeneity of results was assessed and where possible a pooled analysis of sensitivity and specificity was performed using a bivariate analysis with maximum likelihood estimate and 95% confidence intervals (95%CI). We conducted a narrative review on the impact of varying storage conditions or limits of detection in subsets of samples. The QUADAS-2 tool was used to assess risk of bias.ResultsFor the diagnostic accuracy of HBsAg from DBS compared to venous blood, 19 studies were included in a quantitative meta-analysis, and 23 in a narrative review. Pooled sensitivity and specificity were 98% (95%CI:95%–99%) and 100% (95%CI:99–100%), respectively. For the diagnostic accuracy of HCV-Ab from DBS, 19 studies were included in a pooled quantitative meta-analysis, and 23 studies were included in a narrative review. Pooled estimates of sensitivity and specificity were 98% (CI95%:95–99) and 99% (CI95%:98–100), respectively. Overall quality of studies and heterogeneity were rated as moderate in both systematic reviews.ConclusionHCV-Ab and HBsAg testing using DBS compared to venous blood sampling was associated with excellent diagnostic accuracy. However, generalizability is limited as no uniform protocol was applied and most studies did not use fresh samples. Future studies on diagnostic accuracy should include an assessment of impact of environmental conditions common in low resource field settings. Manufacturers also need to formally validate their assays for DBS for use with their commercial assays.

HCV and HBV prevalence based on home blood self-sampling and screening history in the general population in 2016: contribution to the new French screening strategy

“…In particular, compared with the 2004 prevalence survey based on venous blood sampling, the use of DBS in BaroTest may have led to a slight underestimation of CHC and CHB prevalences due to a possible lack of sensitivity. However, several studies, including metaanalyses, have shown excellent diagnostic accuracy (with both specificity and sensitivity higher than 98%) using DBS compared with venous blood sampling for the detection of anti-HCV antibodies, HBs Ag and HCV RNA (33)(34)(35). Although not significant, the observed decrease in CHC prevalence in the general population in metropolitan France may be linked to the decrease in the number of people infected by blood transfusion before 1992, the availability of DAAs, and the almost certain reduction in HCV incidence.…”

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

“…HBsAg laboratory tests have a sensitivity <0.1 IU/mL (Tuaillon et al, 2012), suggesting that even with a dilution factor of 10 or 20 times related to the elution step, the DBS testing may have a better sensitivity than HBsAg RDT. Systematic reviews have reported 98% sensitivity and 100% specificity for HBsAg screening on DBS compared to 88.9% sensitivity and 98.4% specificity using HBsAg RDT Lange et al, 2017a). By contrast, the overall performances of RDT and DBS test dedicated to anti-HCV detection appeared very close, with 98% sensitivity, and 99% specificity using DBS, and 98% sensitivity and 100% sensitivity using RDT (Lange et al, 2017a;Tang et al, 2017).…”

“…Systematic reviews have reported 98% sensitivity and 100% specificity for HBsAg screening on DBS compared to 88.9% sensitivity and 98.4% specificity using HBsAg RDT Lange et al, 2017a). By contrast, the overall performances of RDT and DBS test dedicated to anti-HCV detection appeared very close, with 98% sensitivity, and 99% specificity using DBS, and 98% sensitivity and 100% sensitivity using RDT (Lange et al, 2017a;Tang et al, 2017).…”

Hepatitis C Virus Diagnostics: The Road to Simplification

“…Once in the laboratory, the serum is eluted off the card and can be run using the standard automated serum detection systems. The first spot is tested for Ab, and if positive, the next spot is tested for HCV RNA . Because of the lower quantity of blood, the HCV RNA loads from DBS are lower than in a serum tube from the same patient by ~2 log IU/mL .…”