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Published in: BMC Infectious Diseases 1/2019

Open Access 01-12-2019 | Hepatocellular Carcinoma | Research article

Molecular characterization of hepatitis C virus in liver disease patients in Botswana: a retrospective cross-sectional study

Authors: Lynnette Bhebhe, Motswedi Anderson, Sajini Souda, Wonderful T. Choga, Edward Zumbika, Zachary M. Shaver, Tshepiso Mbangiwa, Bonolo B. Phinius, Chabeni C. Banda, Pinkie Melamu, Rosemary M. Musonda, Max Essex, Jason T. Blackard, Sikhulile Moyo, Simani Gaseitsiwe

Published in: BMC Infectious Diseases | Issue 1/2019

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Abstract

Background

Hepatitis C virus (HCV) infection is a major cause of chronic liver disease globally. Direct acting antivirals (DAAs) have proven effective in curing HCV. However, the current standard of care (SOC) in Botswana remains PEGylated interferon-α (IFN-α) with ribavirin. Several mutations have been reported to confer resistance to interferon-based treatments. Therefore, there is a need to determine HCV genotypes in Botswana, as these data will guide new treatment guidelines and understanding of HCV epidemiology in Botswana.

Methods

This was a retrospective cross-sectional pilot study utilizing plasma obtained from 55 participants from Princess Marina Hospital in Gaborone, Botswana. The partial core region of HCV was amplified, and genotypes were determined using phylogenetic analysis.

Results

Four genotype 5a and two genotype 4v sequences were identified. Two significant mutations – K10Q and R70Q – were observed in genotype 5a sequences and have been associated with increased risk of hepatocellular carcinoma (HCC), while R70Q confers resistance to interferon-based treatments.

Conclusion

Genotypes 5a and 4v are circulating in Botswana. The presence of mutations in genotype 5 suggests that some patients may not respond to IFN-based regimens. The information obtained in this study, in addition to the World health organization (WHO) recommendations, can be utilized by policy makers to implement DAAs as the new SOC for HCV treatment in Botswana.
Literature
2.
go back to reference El-Zanaty F, Way A. Egypt demographic and health survey, 2008. In: Demographic and health survey (EDHS). Cairo: Ministry of Health and Population; 2009. El-Zanaty F, Way A. Egypt demographic and health survey, 2008. In: Demographic and health survey (EDHS). Cairo: Ministry of Health and Population; 2009.
3.
go back to reference Razavi H, Waked I, Sarrazin C, Myers RP, Idilman R, Calinas F, et al. The present and future disease burden of hepatitis C virus (HCV) infection with today’s treatment paradigm. J Viral Hepat. 2014;21:34–59.CrossRef Razavi H, Waked I, Sarrazin C, Myers RP, Idilman R, Calinas F, et al. The present and future disease burden of hepatitis C virus (HCV) infection with today’s treatment paradigm. J Viral Hepat. 2014;21:34–59.CrossRef
4.
go back to reference Agyeman AA, Ofori-Asenso R, Mprah A, Ashiagbor G. Epidemiology of hepatitis C virus in Ghana: a systematic review and meta-analysis. BMC Infect Dis. 2016;16(1):391.CrossRef Agyeman AA, Ofori-Asenso R, Mprah A, Ashiagbor G. Epidemiology of hepatitis C virus in Ghana: a systematic review and meta-analysis. BMC Infect Dis. 2016;16(1):391.CrossRef
6.
go back to reference Wester CW, Bussmann H, Moyo S, Avalos A, Gaolathe T, Ndwapi N, et al. Serological evidence of HIV-associated infection among HIV-1-infected adults in Botswana. Clin Infect Dis. 2006;43(12):1612–5.CrossRef Wester CW, Bussmann H, Moyo S, Avalos A, Gaolathe T, Ndwapi N, et al. Serological evidence of HIV-associated infection among HIV-1-infected adults in Botswana. Clin Infect Dis. 2006;43(12):1612–5.CrossRef
9.
go back to reference Van der Meer AJ. Value anti-hepatitis C virus therapy by its clinical efficacy. Hepatology. 2015;62:334–6.CrossRef Van der Meer AJ. Value anti-hepatitis C virus therapy by its clinical efficacy. Hepatology. 2015;62:334–6.CrossRef
11.
go back to reference Lole KS, Jha JA, Shrotri SP, Tandon BN, Prasad VGM, Arankalle VA. Comparison of hepatitis C virus genotyping by 5 Ј noncoding region- and core-based reverse transcriptase PCR assay with sequencing and use of the assay for determining subtype distribution in India. J Clin Microbiol. 2003;41(11):5240–4.CrossRef Lole KS, Jha JA, Shrotri SP, Tandon BN, Prasad VGM, Arankalle VA. Comparison of hepatitis C virus genotyping by 5 Ј noncoding region- and core-based reverse transcriptase PCR assay with sequencing and use of the assay for determining subtype distribution in India. J Clin Microbiol. 2003;41(11):5240–4.CrossRef
14.
go back to reference Drummond AJ, Suchard MA, Xie D, Rambaut A. Bayesian phylogenetics with BEAUti and the BEAST 1.7. Mol Biol Evol. 2012;29:1969–73.CrossRef Drummond AJ, Suchard MA, Xie D, Rambaut A. Bayesian phylogenetics with BEAUti and the BEAST 1.7. Mol Biol Evol. 2012;29:1969–73.CrossRef
18.
go back to reference Hu Z, Muroyama R, Kowatari N, Chang J, Omata M, Kato N. Characteristic mutations in hepatitis C virus core gene related to the occurrence of hepatocellular carcinoma. Cancer Sci. 2009;100(12):2465–8.CrossRef Hu Z, Muroyama R, Kowatari N, Chang J, Omata M, Kato N. Characteristic mutations in hepatitis C virus core gene related to the occurrence of hepatocellular carcinoma. Cancer Sci. 2009;100(12):2465–8.CrossRef
20.
go back to reference Bull RA, Eltahla AA, Rodrigo C, Koekkoek SM, Walker M, Pirozyan MR, Luciani F. A method for near full-length amplification and sequencing for six hepatitis C virus genotypes. BMC Genomics. 2016;17(1):247.CrossRef Bull RA, Eltahla AA, Rodrigo C, Koekkoek SM, Walker M, Pirozyan MR, Luciani F. A method for near full-length amplification and sequencing for six hepatitis C virus genotypes. BMC Genomics. 2016;17(1):247.CrossRef
21.
go back to reference Sakamoto M, Akahane Y, Tsuda F, Tanaka T, Woodfield DG, Okamoto H. Entire nucleotide sequence and characterization of a hepatitis C virus of genotype V/3a. J Gen Virol. 1994;75(7):1761–8.CrossRef Sakamoto M, Akahane Y, Tsuda F, Tanaka T, Woodfield DG, Okamoto H. Entire nucleotide sequence and characterization of a hepatitis C virus of genotype V/3a. J Gen Virol. 1994;75(7):1761–8.CrossRef
22.
go back to reference Akuta N, Suzuki F, Hirakawa M, Kawamura Y, Yatsuji H, Sezaki H, Suzuki Y, Hosaka T, Kobayashi M, Kobayashi M, Saitoh S, Arase Y, Ikeda K, Chayama K, Nakamura Y, Kumada H. Amino acid substitution in hepatitis C virus core region and genetic variation near the interleukin 28B gene predict viral response to telaprevir with peginterferon and ribavirin. Hepatology. 2010;52:421–9.CrossRef Akuta N, Suzuki F, Hirakawa M, Kawamura Y, Yatsuji H, Sezaki H, Suzuki Y, Hosaka T, Kobayashi M, Kobayashi M, Saitoh S, Arase Y, Ikeda K, Chayama K, Nakamura Y, Kumada H. Amino acid substitution in hepatitis C virus core region and genetic variation near the interleukin 28B gene predict viral response to telaprevir with peginterferon and ribavirin. Hepatology. 2010;52:421–9.CrossRef
23.
go back to reference Nakamoto S, Imazeki F, Fukai K, Fujiwara K, Arai M, Kanda T, Yonemitsu Y, Yokosuka O, Nakamoto S, Imazeki F, Fukai K, Fujiwara K, Arai M, Kanda T, Yonemitsu Y, Yokosuka O. Association between mutations in the core region of hepatitis C virus genotype 1 and hepatocellular carcinoma development. J Hepatol. 2010;52(1):72–8 Erratum in: J Hepatol, 52(4):620.CrossRef Nakamoto S, Imazeki F, Fukai K, Fujiwara K, Arai M, Kanda T, Yonemitsu Y, Yokosuka O, Nakamoto S, Imazeki F, Fukai K, Fujiwara K, Arai M, Kanda T, Yonemitsu Y, Yokosuka O. Association between mutations in the core region of hepatitis C virus genotype 1 and hepatocellular carcinoma development. J Hepatol. 2010;52(1):72–8 Erratum in: J Hepatol, 52(4):620.CrossRef
24.
go back to reference Fishman SL, Factor SH, Balestrieri C, Fan X, Dibisceglie AM, Desai SM, Benson G, Branch AD. Mutations in the hepatitis C virus core gene are associated with advanced liver disease and hepatocellular carcinoma. Clin Cancer Res. 2009;15(9):3205–13.CrossRef Fishman SL, Factor SH, Balestrieri C, Fan X, Dibisceglie AM, Desai SM, Benson G, Branch AD. Mutations in the hepatitis C virus core gene are associated with advanced liver disease and hepatocellular carcinoma. Clin Cancer Res. 2009;15(9):3205–13.CrossRef
29.
go back to reference Gededzha MP, Selabe SG, Kyaw T, Rakgole JN, Blackard JT, Mphahlele MJ. Introduction of new subtypes and variants of hepatitis C virus genotype 4 in South Africa. J Med Virol. 2012;84(4):601–7.CrossRef Gededzha MP, Selabe SG, Kyaw T, Rakgole JN, Blackard JT, Mphahlele MJ. Introduction of new subtypes and variants of hepatitis C virus genotype 4 in South Africa. J Med Virol. 2012;84(4):601–7.CrossRef
30.
go back to reference Iles JC, Raghwani J, Harrison GL, Pepin J, Djoko CF, Tamoufe D, LeBreton M, Schneider BS, Fair JN, Tshala FM, Kayembe PK, Muyembe JJ, Edidi-Basepeo S, Wolfe ND, Simmonds P, Klenerman P, Pybus OG. Phylogeography and epidemic history of hepatitis C virus genotype 4 in Africa. Virology. 2014;464-465:233–43.CrossRef Iles JC, Raghwani J, Harrison GL, Pepin J, Djoko CF, Tamoufe D, LeBreton M, Schneider BS, Fair JN, Tshala FM, Kayembe PK, Muyembe JJ, Edidi-Basepeo S, Wolfe ND, Simmonds P, Klenerman P, Pybus OG. Phylogeography and epidemic history of hepatitis C virus genotype 4 in Africa. Virology. 2014;464-465:233–43.CrossRef
31.
go back to reference Hundie GB, Raj VS, GebreMichael D, Pas SD, Haagmans BL. Genetic diversity of hepatitis C virus in Ethiopia. PLoS One. 2017;12(6):0179064.CrossRef Hundie GB, Raj VS, GebreMichael D, Pas SD, Haagmans BL. Genetic diversity of hepatitis C virus in Ethiopia. PLoS One. 2017;12(6):0179064.CrossRef
32.
go back to reference Quer J, Gregori J, Rodríguez-Frias F, Buti M, Madejon A, Perez-del-Pulgar S, Garcia-Cehic D, Casillas R, Blasi M, Homs M, Tabernero D, Alvarez-Tejado M, Muñoz JM, Cubero M, Caballero A, delCampo JA, Domingo E, Belmonte I, Nieto L, Lens S, Muñoz-de-Rueda P, Sanz-Cameno P, Sauleda S, Bes M, Gomez J, Briones C, Perales C, Sheldon J, Castells L, Viladomiu L, Salmeron J, Ruiz-Extremera A, Quiles-Pérez R, Moreno-Otero R, López-Rodríguez R, Allende H, Romero-Gómez M, Guardia J, Esteban R, Garcia-Samaniego J, Forns X, Esteban JI. High- resolution hepatitis C virus subtyping using NS5B deep sequencing and phylogeny, an alternative to current methods. J Clin Microbiol. 2015;53:219–26. https://doi.org/10.1128/JCM.02093-14.CrossRefPubMed Quer J, Gregori J, Rodríguez-Frias F, Buti M, Madejon A, Perez-del-Pulgar S, Garcia-Cehic D, Casillas R, Blasi M, Homs M, Tabernero D, Alvarez-Tejado M, Muñoz JM, Cubero M, Caballero A, delCampo JA, Domingo E, Belmonte I, Nieto L, Lens S, Muñoz-de-Rueda P, Sanz-Cameno P, Sauleda S, Bes M, Gomez J, Briones C, Perales C, Sheldon J, Castells L, Viladomiu L, Salmeron J, Ruiz-Extremera A, Quiles-Pérez R, Moreno-Otero R, López-Rodríguez R, Allende H, Romero-Gómez M, Guardia J, Esteban R, Garcia-Samaniego J, Forns X, Esteban JI. High- resolution hepatitis C virus subtyping using NS5B deep sequencing and phylogeny, an alternative to current methods. J Clin Microbiol. 2015;53:219–26. https://​doi.​org/​10.​1128/​JCM.​02093-14.CrossRefPubMed
33.
go back to reference Prabdial-Sing N, Blackard JT, Puren AJ, Mahomed A, Abuelhassan W, Mahlangu J, Vermeulen M, Bowyer SM. Naturally occurring resistance mutations within the core and NS5B regions in hepatitis C genotypes, particularly genotype 5a, in South Africa. Antivir Res. 2016;127:90–8.CrossRef Prabdial-Sing N, Blackard JT, Puren AJ, Mahomed A, Abuelhassan W, Mahlangu J, Vermeulen M, Bowyer SM. Naturally occurring resistance mutations within the core and NS5B regions in hepatitis C genotypes, particularly genotype 5a, in South Africa. Antivir Res. 2016;127:90–8.CrossRef
Metadata
Title
Molecular characterization of hepatitis C virus in liver disease patients in Botswana: a retrospective cross-sectional study
Authors
Lynnette Bhebhe
Motswedi Anderson
Sajini Souda
Wonderful T. Choga
Edward Zumbika
Zachary M. Shaver
Tshepiso Mbangiwa
Bonolo B. Phinius
Chabeni C. Banda
Pinkie Melamu
Rosemary M. Musonda
Max Essex
Jason T. Blackard
Sikhulile Moyo
Simani Gaseitsiwe
Publication date
01-12-2019
Publisher
BioMed Central
Published in
BMC Infectious Diseases / Issue 1/2019
Electronic ISSN: 1471-2334
DOI
https://doi.org/10.1186/s12879-019-4514-1

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