Highly Diverse Hepatitis C Strains Detected in Sub-Saharan Africa Have Unknown Susceptibility to Direct-Acting Antiviral Treatments
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Date
2019
Journal Title
Journal ISSN
Volume Title
Publisher
Hepatology
Abstract
The global plan to eradicate hepatitis C virus (HCV) led by the World Health Organization outlines the use of
highly effective direct-acting antiviral drugs (DAAs) to achieve elimination by 2030. Identifying individuals with
active disease and investigation of the breadth of diversity of the virus in sub-Saharan Africa (SSA) is essential as
genotypes in this region (where very few clinical trials have been carried out) are distinct from those found in other
parts of the world. We undertook a population-based, nested case-control study in Uganda and obtained additional
samples from the Democratic Republic of Congo (DRC) to estimate the prevalence of HCV, assess strategies for
disease detection using serological and molecular techniques, and characterize genetic diversity of the virus. Using
next-generation and Sanger sequencing, we aimed to identify strains circulating in East and Central Africa. A total
of 7,751 Ugandan patients were initially screened for HCV, and 20 PCR-positive samples were obtained for sequencing.
Serological assays were found to vary significantly in specificity for HCV. HCV strains detected in Uganda
included genotype (g) 4k, g4p, g4q, and g4s and a newly identified unassigned g7 HCV strain. Two additional
unassigned g7 strains were identified in patients originating from DRC (one partial and one full open reading frame
sequence). These g4 and g7 strains contain nonstructural (ns) protein 3 and 5A polymorphisms associated with resistance
to DAAs in other genotypes. Clinical studies are therefore indicated to investigate treatment response in
infected patients. Conclusion: Although HCV prevalence and genotypes have been well characterized in patients in
well-resourced countries, clinical trials are urgently required in SSA, where highly diverse g4 and g7 strains circulate.
Description
Keywords
Hepatitis C Strains, Sub-Saharan Africa, Antiviral Treatments
Citation
Davis, C., Mgomella, G. S., da Silva Filipe, A., Frost, E. H., Giroux, G., Hughes, J., ... & Thomson, E. C. (2019). Highly diverse hepatitis C strains detected in Sub‐Saharan Africa have unknown susceptibility to direct‐acting antiviral treatments. Hepatology, 69(4), 1426-1441. DOI 10.1002/hep.30342