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

Davis, C. et al. (2019) New highly diverse hepatitis C strains detected in sub‐Saharan Africa have unknown susceptibility to direct‐acting antiviral treatments. Hepatology, 69(4), pp. 1426-1441. (doi:10.1002/hep.30342) (PMID:30387174) (PMCID:PMC6492010)

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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.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Thomson, Dr Emma and Hughes, Dr Joseph and Niebel, Mr Marc and Vattipally, Dr Sreenu and Da Silva Filipe, Dr Ana and Davis, Dr Christopher and McLauchlan, Professor John and Singer, Dr Joshua
Authors: Davis, C., Mgomella, G. S., da silva Filipe, A., Frost, E. H., Giroux, G., Hughes, J., Hogan, C., Kaleebu, P., Asiki, G., McLauchlan, J., Niebel, M., Ocama, P., Pomila, C., Pybus, O. G., Pépin, J., Simmonds, P., Singer, J. B., Sreenu, V. B., Wekesa, C., Young, E. H., Murphy, D. G., Sandhu, M., and Thomson, E. C.
College/School:College of Medical Veterinary and Life Sciences > Institute of Infection Immunity and Inflammation
Journal Name:Hepatology
Publisher:Wiley
ISSN:0270-9139
ISSN (Online):1527-3350
Published Online:02 November 2018
Copyright Holders:Copyright © 2018 American Association for the Study of Liver Disease
First Published:First published in Hepatology 69(4):1426-1441
Publisher Policy:Reproduced in accordance with the publisher copyright policy

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
656341Virus-host interactions in hepatitis C virus infectionJohn McLauchlanMedical Research Council (MRC)MC_UU_12014/1MVLS III - CENTRE FOR VIRUS RESEARCH
645101T-cell mediated evolution of hepatitis C virus during acute infectionEmma ThomsonWellcome Trust (WELLCOTR)102789/Z/13/ZMVLS III - CENTRE FOR VIRUS RESEARCH
3007420Accelerating Precision Diagnostics - Bridging the GapAnna DominiczakMedical Research Council (MRC)MC_PC_16045CAMS - Cardiovascular Science