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Original Research
Hepatitis C missed diagnostic opportunities: The role of reflex viral load testing in the era of direct acting antivirals, a descriptive South African study from 2017 to 2021
Submitted: 18 August 2025 | Published: 27 March 2026
About the author(s)
Hloniphile Mthiyane, Department of Medical Virology, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South AfricaBonolo Mashishi, Department of Medical Virology, Faculty of Health Sciences, University of Pretoria, Pretoria, South Africa; and Department of Medical Virology, National Health Laboratory Service, Johannesburg, South Africa
Mamodiane A. Patjane, Department of Medical Virology, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa
Ntwanano Honwana, Department of Medical Virology, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa
Nishi Prabdial-Sing, Department of Medical Virology, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa; and National Institute for Communicable Diseases, National Health Laboratory Service, Johannesburg, South Africa
Lucia Hans, National Priority Programme, National Health Laboratory Service, Johannesburg, South Africa; and Wits Diagnostic Innovation Hub, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa
Nonhlanhla Mbenenge, Department of Medical Virology, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa; and Department of Medical Virology, National Health Laboratory Service, Johannesburg, South Africa
Bhaveshan Reddy, Department of Medical Virology, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg; and Department of Medical Virology, National Health Laboratory Service, Johannesburg, South Africa
Avania Bangalee, Department of Medical Virology, Lancet Laboratories, Johannesburg, South Africa, South Africa
Florette K. Treurnicht, Department of Medical Virology, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg; and Department of Medical Virology, National Health Laboratory Service, Johannesburg, South Africa
Abstract
Background: The hepatitis C virus (HCV) testing algorithm used in South African laboratories involves two tests; a serology test to detect anti-HCV antibodies and a confirmatory test to detect the presence of HCV ribonucleic acid (RNA). These tests usually require consecutive blood samples taken at more than one hospital visit, leaving patients with inconclusive diagnosis for weeks.
Objectives: This study aimed to describe the prevalence and proportion of HCV seropositive cases where diagnostic opportunities were missed among patients who attended public healthcare facilities in Johannesburg, South Africa.
Method: This descriptive study was conducted as a retrospective analysis of laboratory data from the Department of Medical Virology, National Health Laboratory Service, Johannesburg, South Africa. Patients for whom HCV diagnosis were requested from 2017 to 2021 were included in the study.
Results: Over the five-year period, a total of 212 670 patients were tested for HCV antibodies and 8575 (4.04%) tested positive. The HCV seropositivity was recorded for 74.8% (6421/8575) of males compared to females (23.6%; 2030/8575; p < 0.001). Only 25% (2183/8575) of HCV seropositive patients had a linked HCV RNA quantitative PCR test result.
Conclusion: Despite an overall HCV seroprevalence of 4% in this study, only one quarter received a definitive diagnosis. This highlights that most patients are lost to follow-up because of the two-step diagnostic process, which requires them to return to the health facility for confirmatory tests.
Contribution: The study highlights the need to adopt HCV reflex testing as the standard in South Africa to meet the 2030 elimination targets.
Keywords
Sustainable Development Goal
Metrics
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