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Hepatology. 2018 Nov 2. doi: 10.1002/hep.30342. [Epub ahead of print]

New highly diverse hepatitis C strains detected in sub-Saharan Africa have unknown susceptibility to direct-acting antiviral treatments.

Author information

1
MRC-University of Glasgow Centre for Virus Research, 464 Bearsden Road, Glasgow, UK, G61 1QH.
2
Department of Medicine, University of Cambridge, Cambridge, Cambridgeshire, UK.
3
Wellcome Sanger Institute, Hinxton, Cambridgeshire, UK, CB10 1SA.
4
Université de Sherbrooke, Sherbrooke, Québec, Canada, J1H 5N4.
5
Medical Research Council/Uganda Virus Research Institute & London School of Hygiene and Tropical Medicine Uganda Research Unit, Plot 51 -59, Nakiwogo Road, Entebbe 49, Uganda.
6
Uganda Virus Research Institute, Plot No.:51 -59, Nakiwogo Road, Entebbe 49, Uganda.
7
Department of Medicine, Makerere University College of Health Sciences, Kampala, Uganda.
8
Dept of Zoology, University of Oxford, South Parks Road, Oxford, OX1 3PS.
9
Peter Medawar Building for Pathogen Research, University of Oxford, UK, OX1 3SY.
10
Institut national de santé publique du Québec Laboratoire de santé publique du Québec, Sainte-Anne-de-Bellevue, Québec, Canada.

Abstract

BACKGROUND AND RATIONALE FOR THE STUDY:

The global plan to eradicate hepatitis C (HCV) led by the World Health Organisation (WHO) 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 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 characterise genetic diversity of the virus. Using next generation (NGS) and Sanger sequencing, we aimed to identify strains circulating in East and Central Africa.

MAIN RESULTS:

7751 Ugandan patients were initially screened for HCV and 20 PCR positive samples obtained for sequencing. Serological assays were found to vary significantly in specificity for HCV. HCV strains detected in Uganda included genotypes (g) 4k, 4p, 4q and 4s and a new unassigned genotype 7 HCV strain. Two additional unassigned g7 strains were identified in patients originating from DRC (one partial and one full ORF sequence). These g4 and 7 strains contain NS3 and NS5A polymorphisms associated with resistance to DAAs in other genotypes. Clinical studies are therefore indicated to investigate treatment response in infected patients.

CONCLUSION:

While HCV prevalence and genotypes have been well characterised in patients in well-resourced countries, clinical trials are urgently required in SSA where highly diverse g4 and 7 strains circulate. This article is protected by copyright. All rights reserved.

KEYWORDS:

DRC ; HCV ; NGS ; Africa; Uganda

PMID:
30387174
DOI:
10.1002/hep.30342

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