Laboratory-based dried blood spot testing for hepatitis C: A protocol for systematic review and meta-analysis of diagnostic accuracy

Background: Diagnosis of chronic hepatitis C virus (HCV) infection typically involves collection of venous blood samples prior to serological investigation of an antibody response followed by a confirmatory viral load or antigen test to verify active HCV infection. This conventional pathway poses logistical challenges for the implementation of reflex testing, whereby the confirmatory test is performed on the same sample used for serological investigation. Dried blood spot (DBS) testing, in which capillary blood is deposited on filter paper, is a less invasive alternative that can enable reflex testing without the need for venepuncture, centrifugation and freezing of samples. Methods: This systematic review aims to assess the diagnostic accuracy of DBS compared with venous blood samples for diagnosis of chronic HCV infection. Observational studies which compare diagnostic tests using DBS with those using serum, plasma or whole blood in patients with chronic or resolved HCV infection will be included. Electronic searches will be conducted in PubMed, Embase, Scopus, Web of Science, Lilacs and the Cochrane library. Citation screening, data extraction and quality appraisal of included studies will be performed in duplicate using the Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2) tool. A meta-analysis will be conducted to derive pooled estimates of sensitivity, specificity, positive likelihood ratios, negative likelihood ratios, and diagnostic odds ratios. Sensitivity analyses and meta-regression will also be performed. Quality of the evidence will be evaluated using the GRADE criteria. Discussion: Identifying and linking people with currently undiagnosed chronic HCV infection to care is pivotal to attaining global viral hepatitis elimination targets. The use of DBS could simplify diagnostic testing strategies by integrating reflex testing into the care pathway and reducing drop-off along the cascade of care. Registration: PROSPERO, CRD42020205204. Registered 19 (th) September 2020.