Laboratory‐based testing for hepatitis C infection using dried blood spot samples: A systematic review and meta‐analysis of diagnostic accuracy

Abstract

The use of dried blood spot (DBS) samples can facilitate the implementation of reflex testing by circumventing the need for centrifugation and freezing of venous blood samples. This systematic review assessed the accuracy of using DBS samples to diagnose chronic hepatitis C virus (HCV) infection. A comprehensive search was undertaken to identify articles published up to July 2020 evaluating the diagnostic accuracy of anti-HCV, HCV-RNA and HCV core antigen tests using DBS. Screening, data extraction, quality appraisal and Grading of Recommendations, Assessment, Development and Evaluations certainty of the evidence assessment were performed independently by two reviewers. Meta-analysis, meta-regression and sensitivity analyses were conducted. The evidence demonstrates that laboratorybased anti-HCV and HCV-RNA tests using DBS samples have high diagnostic accuracy. All comparisons were between DBS and venous samples. For the detection of anti-HCV, sensitivity was 95% (95% CI: 92%-97%) and specificity was 99% ([95% CI: 98%-99%]; n = 25; I 2 = 81%; moderate certainty). For the detection of HCV-RNA, the sensitivity was 95% (95% CI: 93%-97%) and specificity was 97% ([95% CI: 94%-98%]; n = 20; I 2 = 52%; moderate certainty). The sensitivity of HCV core antigen tests was 86% (95% CI: 79%-91%) and specificity was 98% ([95% CI: 94%-99%]; n = 5; I 2 = 37%; low certainty) compared with HCV-RNA (the gold standard for detecting chronic HCV). DBS samples could facilitate diagnosis of chronic HCV infection as the necessary sequential tests (anti-HCV and then HCV-RNA or HCV core antigen) can be undertaken using the same blood sample. This could reduce loss of patient follow-up and support international efforts towards HCV elimination in both high and low prevalence settings.

Validation of dried blood spots for capturing hepatitis C virus diversity for genomic surveillance

“…Previous studies using DBS have demonstrated its reliability in detecting RNA, antibodies and drug resistance-associated substitutions. 2,9,10 The provision of such alternative diagnosis approaches to low-income, remote and hardto-reach populations may help close the gaps in eliminating HCV by 2030. Therefore, using DBS as an alternative means for genomic sequencing efforts could empower HCV surveillance initiatives and enable point-of-care genomic analysis.…”

“…In addition, DBS specimens once completely dried are considered noninfectious and nonhazardous allowing them to be shipped and transported at ambient temperatures. Previous studies using DBS have demonstrated its reliability in detecting RNA, antibodies and drug resistance‐associated substitutions 2,9,10 . The provision of such alternative diagnosis approaches to low‐income, remote and hard‐to‐reach populations may help close the gaps in eliminating HCV by 2030.…”

“…DBS samples are easy to collect, transport, and store, and they can be used for a wide range of diagnostic tests, including ELISA and PCR‐based virus detection. Several studies have investigated the use of DBS for HCV testing and have reported comparable diagnostic performance to traditional plasma samples 2 . However, no previous study has demonstrated the feasibility of using DBS to examine the genetic diversity of HCV in the context of potential outbreak investigations.…”

“…Several studies have investigated the use of DBS for HCV testing and have reported comparable diagnostic performance to traditional plasma samples. 2 However, no previous study has demonstrated the feasibility of using DBS to examine the genetic diversity of HCV in the context of potential outbreak investigations.…”

Validation of a novel automated system, Fluispotter®, for serial sampling of dried blood spots

“…The interassay accuracy and precision were less than 10% across a range of different hematocrit values ( 7 ). DBS technology is increasingly being recognized as a valuable alternative to plasma sampling ( 8 ) and is potentially used in different scenarios such as testing for hepatitis C infection ( 9 ) or monitoring of anticancer drugs ( 10 ), screening at-risk populations for various diseases ( 11 ), and general screening ( 12 ). The analytical part has similarly advanced from manual handling of DBS samples to a combination of liquid chromotography-tandem mass spectrometry ( 13 ) and robotic DBS extraction systems allowing a fully automated analytical process of DBS ( 14 ).…”