Diagnostic Accuracy of Point-of-Care HCV Viral Load Assays for HCV Diagnosis: A Systematic Review and Meta-Analysis

Abstract

Despite the widespread availability of curative treatment with direct-acting antivirals, a significant proportion of people with HCV remain undiagnosed and untreated. New point-of-care (PoC) HCV RNA assays that can be used in clinical settings may help expand access to testing and treatment. This study aimed to evaluate the diagnostic performance of PoC HCV viral load assays compared to laboratory-based testing. Methods: We searched three databases for studies published before May 2021 that evaluated PoC HCV RNA assays against a laboratory NAT reference standard (Prospero CRD42021269022). Random effects bivariate models were used to summarize the estimates. Stratified analyses were performed based on geographic region, population (PWID, etc.), and specimen type (serum/plasma or fingerstick; fresh or frozen). We used the GRADE approach to assess the certainty of the evidence. Results: A total of 25 studies were eligible. We evaluated five different commercially available viral load assays. The pooled sensitivity and specificity were 99% (95% CI: 98−99%) and 99% (95% CI: 99−100%), respectively. High sensitivity and specificity were observed across different assays, study settings (including LMICs and HICs), and populations. There was a small but statistically significant reduction in sensitivity for fingersticks compared to serum or plasma samples (98% vs. 100%, p < 0.05), but the specificity was similar between frozen and fresh samples. The evidence was rated as moderate-high certainty. Conclusions: PoC HCV viral load assays demonstrate excellent diagnostic performance in various settings and populations. The WHO now recommends using PoC HCV viral load assays as an additional strategy to promote access to confirmatory viral load testing and treatment.

Keywords: diagnostic accuracy; hepatitis c; point-of-care; viral load testing.

Figure 1

* Consider, if feasible to do so, reporting the number of records identified from each database or register searched (rather than the total number across all databases/registers). ** If automation tools were used, indicate how many records were excluded by a human and how many were excluded by automation tools. From: http://www.prisma-statement.org/ (accessed on 1 September 2021).

Figure 2

Geographic distribution of countries from 25 studies included within the review (shaded in red). WHO regions: Africa—Cameroon (n = 3), Nigeria (n = 1), Senegal (n = 1), South Africa (n = 1), and Tanzania (n = 1). Americas—the United States (n = 2). Europe—Belgium (n = 1), France (n = 2), Georgia (n = 4), Greece (n = 1), Italy (n = 1), Spain (n = 1), Switzerland (n = 1), UK (n = 1), and Ukraine (n = 2). South-east Asia—India (n = 3), Indonesia (n = 2), and Thailand (n = 1). West Pacific—Australia (n = 4), Cambodia (n = 1), and Malaysia (n = 1).

Figure 3

Quality assessment of Diagnostic Accuracy Studies 2 (QUADAS-2) study quality summary.

Figure 4

(a) Meta–analysis of diagnostic accuracy (sensitivity and specificity) for point–of–care HCV RNA assays for the diagnosis of chronic HCV infection (62 data sets from 25 studies). (b) Meta–analysis of diagnostic accuracy (sensitivity and specificity) for point–of–care HCV RNA assays for the diagnosis of chronic HCV infection (Xpert HCV Viral Load) (13 data sets from 12 studies). (c) Meta–analysis of diagnostic accuracy (sensitivity and specificity) for point–of–care HCV RNA assays for the diagnosis of chronic HCV infection (Xpert HCV VL Fingerstick) (25 data sets from 6 studies). (d) Meta–analysis of diagnostic accuracy (sensitivity and specificity) for point–of–care HCV RNA assays for the diagnosis of chronic HCV infection (Genedrive HCV ID kit) (11 data sets from 6 studies). (e) Meta–analysis of diagnostic accuracy (sensitivity and specificity) for point–of–care HCV RNA assays for the diagnosis of chronic HCV infection (Truenat and SAMBA) (13 data sets from 3 studies).

Figure 4

(a) Meta–analysis of diagnostic accuracy (sensitivity and specificity) for point–of–care HCV RNA assays for the diagnosis of chronic HCV infection (62 data sets from 25 studies). (b) Meta–analysis of diagnostic accuracy (sensitivity and specificity) for point–of–care HCV RNA assays for the diagnosis of chronic HCV infection (Xpert HCV Viral Load) (13 data sets from 12 studies). (c) Meta–analysis of diagnostic accuracy (sensitivity and specificity) for point–of–care HCV RNA assays for the diagnosis of chronic HCV infection (Xpert HCV VL Fingerstick) (25 data sets from 6 studies). (d) Meta–analysis of diagnostic accuracy (sensitivity and specificity) for point–of–care HCV RNA assays for the diagnosis of chronic HCV infection (Genedrive HCV ID kit) (11 data sets from 6 studies). (e) Meta–analysis of diagnostic accuracy (sensitivity and specificity) for point–of–care HCV RNA assays for the diagnosis of chronic HCV infection (Truenat and SAMBA) (13 data sets from 3 studies).

Figure 4

(a) Meta–analysis of diagnostic accuracy (sensitivity and specificity) for point–of–care HCV RNA assays for the diagnosis of chronic HCV infection (62 data sets from 25 studies). (b) Meta–analysis of diagnostic accuracy (sensitivity and specificity) for point–of–care HCV RNA assays for the diagnosis of chronic HCV infection (Xpert HCV Viral Load) (13 data sets from 12 studies). (c) Meta–analysis of diagnostic accuracy (sensitivity and specificity) for point–of–care HCV RNA assays for the diagnosis of chronic HCV infection (Xpert HCV VL Fingerstick) (25 data sets from 6 studies). (d) Meta–analysis of diagnostic accuracy (sensitivity and specificity) for point–of–care HCV RNA assays for the diagnosis of chronic HCV infection (Genedrive HCV ID kit) (11 data sets from 6 studies). (e) Meta–analysis of diagnostic accuracy (sensitivity and specificity) for point–of–care HCV RNA assays for the diagnosis of chronic HCV infection (Truenat and SAMBA) (13 data sets from 3 studies).

Figure 5

Hierarchical summary receiver-operator curve for the diagnostic accuracy of point-of-care HCV RNA assays used to diagnose chronic HCV infection. (Overall, with all studies combined).