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Published in: Virology Journal 1/2016

Open Access 01-12-2016 | Research

Serologic and genotypic characterization of hepatitis B virus in HIV-1 infected patients from South West and Littoral Regions of Cameroon

Authors: Tshifhiwa Magoro, George Gachara, Lufuno Mavhandu, Emmaculate Lum, Helen K. Kimbi, Roland N. Ndip, Pascal Bessong

Published in: Virology Journal | Issue 1/2016

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Abstract

Background

HBV and HIV share similar transmission routes. Concurrent infection with the two viruses usually results in more severe and progressive liver disease, and a higher incidence of cirrhosis, liver cancer and mortality. Further, this co-infection may lead to cross-resistance between HIV and HBV drugs and increased liver injury, either due to direct hepatotoxicity or drug-related immune-reconstitution hepatitis. These challenges necessitate continuous surveillance for HBV among HIV infected individuals to guide patient management. We conducted this study to understand the serologic and genotypic characteristics of HBV among HIV/HBV infected patients in South West and Littoral Regions of Cameroon.

Methods

Plasma samples were screened for HBsAg, HBeAg, Anti-HBs and anti-HBc using ELISA followed by DNA extraction from all HBsAg positive samples. A 366 bp region covering the overlapping surface/polymerase gene was amplified by a nested PCR and the product sequenced using Big Dye sequencing chemistry. The resulting sequences were then analyzed for genotypes and both escape and drug resistance mutations.

Results

Of the 455 samples in this study, 25.5 % (n = 116) were HBsAg positive and 46 of these had their DNA successfully amplified. Genotype E was found in 32 samples (69.6 %) and genotype A in the rest of the samples. Escape mutations associated with failure of diagnosis (Y100C, R122K and Q129H) and with vaccine escape (Q129R and T131N) were detected in varying frequencies in the population. Polymerase mutations implicated in resistance to lamivudine and other ʟ-nucleoside analogues were detected in seven patients (15.2 %), while all the samples lacked mutations associated with resistance to adefovir and tenofovir.

Conclusions

These findings suggest the endemicity of HBV and the predominance of genotypes A and E in the study population. Also, drug resistance findings support the use of tenofovir based ART regimens among HIV/HBV co-infected persons. There is need for continuous HBV screening and monitoring in HIV infected individuals in these regions.
Literature
2.
go back to reference Simmonds P. The origin and evolution of hepatitis viruses in humans. J Gen Virol. 2001;82(Pt 4):693–712.CrossRefPubMed Simmonds P. The origin and evolution of hepatitis viruses in humans. J Gen Virol. 2001;82(Pt 4):693–712.CrossRefPubMed
3.
go back to reference Forbi JC, Ben-Ayed Y, Xia GL, Vaughan G, Drobeniuc J, Switzer WM, Khudyakov YE. Disparate distribution of hepatitis B virus genotypes in four sub-Saharan African countries. J Clin Virol. 2013;58(1):59–66.CrossRefPubMedPubMedCentral Forbi JC, Ben-Ayed Y, Xia GL, Vaughan G, Drobeniuc J, Switzer WM, Khudyakov YE. Disparate distribution of hepatitis B virus genotypes in four sub-Saharan African countries. J Clin Virol. 2013;58(1):59–66.CrossRefPubMedPubMedCentral
4.
go back to reference Bonino F, Piratvisuth T, Brunetto MR, Liaw YF. Diagnostic markers of chronic hepatitis B infection and disease. Antivir Ther. 2010;15 Suppl 3:35–44.CrossRefPubMed Bonino F, Piratvisuth T, Brunetto MR, Liaw YF. Diagnostic markers of chronic hepatitis B infection and disease. Antivir Ther. 2010;15 Suppl 3:35–44.CrossRefPubMed
5.
go back to reference Tanwar S, Dusheiko G. Is there any value to hepatitis B virus genotype analysis? Curr Gastroenterol Rep. 2012;14(1):37–46.CrossRefPubMed Tanwar S, Dusheiko G. Is there any value to hepatitis B virus genotype analysis? Curr Gastroenterol Rep. 2012;14(1):37–46.CrossRefPubMed
6.
go back to reference Hernandez S, Venegas M, Brahm J, Villanueva RA. Full-genome sequence of a hepatitis B virus genotype f1b clone from a chronically infected Chilean patient. Genome Announcements. 2014;2(5). doi:10.1128/genomeA.01075-14. Hernandez S, Venegas M, Brahm J, Villanueva RA. Full-genome sequence of a hepatitis B virus genotype f1b clone from a chronically infected Chilean patient. Genome Announcements. 2014;2(5). doi:10.​1128/​genomeA.​01075-14.
7.
go back to reference Kramvis A, Kew MC. Relationship of genotypes of hepatitis B virus to mutations, disease progression and response to antiviral therapy. J Viral Hepat. 2005;12(5):456–64.CrossRefPubMed Kramvis A, Kew MC. Relationship of genotypes of hepatitis B virus to mutations, disease progression and response to antiviral therapy. J Viral Hepat. 2005;12(5):456–64.CrossRefPubMed
8.
go back to reference McMahon BJ. The influence of hepatitis B virus genotype and subgenotype on the natural history of chronic hepatitis B. Hepatol Int. 2009;3(2):334–42.CrossRefPubMed McMahon BJ. The influence of hepatitis B virus genotype and subgenotype on the natural history of chronic hepatitis B. Hepatol Int. 2009;3(2):334–42.CrossRefPubMed
9.
go back to reference Alter MJ. Epidemiology of viral hepatitis and HIV co-infection. J Hepatol. 2006;44(1 Suppl):S6–9.CrossRefPubMed Alter MJ. Epidemiology of viral hepatitis and HIV co-infection. J Hepatol. 2006;44(1 Suppl):S6–9.CrossRefPubMed
10.
go back to reference Gomez-Gonzalo M, Carretero M, Rullas J, Lara-Pezzi E, Aramburu J, Berkhout B, Alcami J, Lopez-Cabrera M. The hepatitis B virus X protein induces HIV-1 replication and transcription in synergy with T-cell activation signals: functional roles of NF-kappaB/NF-AT and SP1-binding sites in the HIV-1 long terminal repeat promoter. J Biol Chem. 2001;276(38):35435–43.CrossRefPubMed Gomez-Gonzalo M, Carretero M, Rullas J, Lara-Pezzi E, Aramburu J, Berkhout B, Alcami J, Lopez-Cabrera M. The hepatitis B virus X protein induces HIV-1 replication and transcription in synergy with T-cell activation signals: functional roles of NF-kappaB/NF-AT and SP1-binding sites in the HIV-1 long terminal repeat promoter. J Biol Chem. 2001;276(38):35435–43.CrossRefPubMed
11.
12.
go back to reference Hache C, Villeneuve JP. Lamivudine treatment in patients with chronic hepatitis B and cirrhosis. Expert Opin Pharmacother. 2006;7(13):1835–43.CrossRefPubMed Hache C, Villeneuve JP. Lamivudine treatment in patients with chronic hepatitis B and cirrhosis. Expert Opin Pharmacother. 2006;7(13):1835–43.CrossRefPubMed
13.
go back to reference Liaw YF, Sung JJ, Chow WC, Farrell G, Lee CZ, Yuen H, Tanwandee T, Tao QM, Shue K, Keene ON, et al. Lamivudine for patients with chronic hepatitis B and advanced liver disease. N Engl J Med. 2004;351(15):1521–31.CrossRefPubMed Liaw YF, Sung JJ, Chow WC, Farrell G, Lee CZ, Yuen H, Tanwandee T, Tao QM, Shue K, Keene ON, et al. Lamivudine for patients with chronic hepatitis B and advanced liver disease. N Engl J Med. 2004;351(15):1521–31.CrossRefPubMed
14.
go back to reference Fouelifack Ymele F, Keugoung B, Fouedjio JH, Kouam N, Mendibi S, Dongtsa Mabou J. High Rates of Hepatitis B and C and HIV Infections among Blood Donors in Cameroon: A Proposed Blood Screening Algorithm for Blood Donors in Resource-Limited Settings. J Blood Transfusion. 2012;2012:7.CrossRef Fouelifack Ymele F, Keugoung B, Fouedjio JH, Kouam N, Mendibi S, Dongtsa Mabou J. High Rates of Hepatitis B and C and HIV Infections among Blood Donors in Cameroon: A Proposed Blood Screening Algorithm for Blood Donors in Resource-Limited Settings. J Blood Transfusion. 2012;2012:7.CrossRef
15.
go back to reference Noubiap JJ, Aka PV, Nanfack AJ, Agyingi LA, Ngai JN, Nyambi PN. Hepatitis B and C Co-Infections in Some HIV-Positive Populations in Cameroon, West Central Africa: Analysis of Samples Collected Over More Than a Decade. PLoS ONE. 2015;10(9):e0137375.CrossRefPubMedPubMedCentral Noubiap JJ, Aka PV, Nanfack AJ, Agyingi LA, Ngai JN, Nyambi PN. Hepatitis B and C Co-Infections in Some HIV-Positive Populations in Cameroon, West Central Africa: Analysis of Samples Collected Over More Than a Decade. PLoS ONE. 2015;10(9):e0137375.CrossRefPubMedPubMedCentral
16.
go back to reference Romina S, Joseph F, Laura C, Maria-Mercedes S, Aubin N, Samuel Martin S, Mathurin K, Valeria C, Judith T, Loredana S, et al. High Burden of HBV-Infection and Atypical HBV Strains among HIV-infected Cameroonians. Curr HIV Res. 2016;14(2):165–71.CrossRef Romina S, Joseph F, Laura C, Maria-Mercedes S, Aubin N, Samuel Martin S, Mathurin K, Valeria C, Judith T, Loredana S, et al. High Burden of HBV-Infection and Atypical HBV Strains among HIV-infected Cameroonians. Curr HIV Res. 2016;14(2):165–71.CrossRef
17.
go back to reference Marrone A, Zampino R, Karayannis P, Cirillo G, Cesaro G, Guerrera B, Ricciotti R, del Giudice EM, Utili R, Adinolfi LE, et al. Clinical reactivation during lamivudine treatment correlates with mutations in the precore/core promoter and polymerase regions of hepatitis B virus in patients with anti-hepatitis B e-positive chronic hepatitis. Aliment Pharmacol Ther. 2005;22(8):707–14.CrossRefPubMed Marrone A, Zampino R, Karayannis P, Cirillo G, Cesaro G, Guerrera B, Ricciotti R, del Giudice EM, Utili R, Adinolfi LE, et al. Clinical reactivation during lamivudine treatment correlates with mutations in the precore/core promoter and polymerase regions of hepatitis B virus in patients with anti-hepatitis B e-positive chronic hepatitis. Aliment Pharmacol Ther. 2005;22(8):707–14.CrossRefPubMed
18.
go back to reference Tamura K, Stecher G, Peterson D, Filipski A, Kumar S. MEGA6: Molecular Evolutionary Genetics Analysis version 6.0. Mol Biol Evol. 2013;30(12):2725–9.CrossRefPubMedPubMedCentral Tamura K, Stecher G, Peterson D, Filipski A, Kumar S. MEGA6: Molecular Evolutionary Genetics Analysis version 6.0. Mol Biol Evol. 2013;30(12):2725–9.CrossRefPubMedPubMedCentral
19.
go back to reference Kimura M. A simple method for estimating evolutionary rates of base substitutions through comparative studies of nucleotide sequences. J Mol Evol. 1980;16(2):111–20.CrossRefPubMed Kimura M. A simple method for estimating evolutionary rates of base substitutions through comparative studies of nucleotide sequences. J Mol Evol. 1980;16(2):111–20.CrossRefPubMed
21.
go back to reference Frambo AAB, Atashili J, Fon PN, Ndumbe PM. Prevalence of HBsAg and knowledge about hepatitis B in pregnancy in the Buea Health District, Cameroon: a cross-sectional study. BMC Res Notes. 2014;7:394.CrossRefPubMedPubMedCentral Frambo AAB, Atashili J, Fon PN, Ndumbe PM. Prevalence of HBsAg and knowledge about hepatitis B in pregnancy in the Buea Health District, Cameroon: a cross-sectional study. BMC Res Notes. 2014;7:394.CrossRefPubMedPubMedCentral
22.
go back to reference Ducancelle A, Abgueguen P, Birguel J, Mansour W, Pivert A, Guillou-Guillemette H, Sobnangou J-J, Rameau A, Huraux J-M, Lunel-Fabiani F. High endemicity and low molecular diversity of hepatitis B virus infections in pregnant women in a rural district of North Cameroon. PLoS ONE. 2013;8. Ducancelle A, Abgueguen P, Birguel J, Mansour W, Pivert A, Guillou-Guillemette H, Sobnangou J-J, Rameau A, Huraux J-M, Lunel-Fabiani F. High endemicity and low molecular diversity of hepatitis B virus infections in pregnant women in a rural district of North Cameroon. PLoS ONE. 2013;8.
23.
go back to reference Stabinski L, O’Connor S, Barnhart M, Kahn RJ, Hamm TE. Prevalence of HIV and hepatitis B virus co-infection in sub-Saharan Africa and the potential impact and program feasibility of hepatitis B surface antigen screening in resource-limited settings. J Acquir Immune Defic Syndr. 2015;68 Suppl 3:S274–85.CrossRefPubMed Stabinski L, O’Connor S, Barnhart M, Kahn RJ, Hamm TE. Prevalence of HIV and hepatitis B virus co-infection in sub-Saharan Africa and the potential impact and program feasibility of hepatitis B surface antigen screening in resource-limited settings. J Acquir Immune Defic Syndr. 2015;68 Suppl 3:S274–85.CrossRefPubMed
24.
go back to reference Andersson MI, Rajbhandari R, Kew MC, Vento S, Preiser W, Hoepelman AIM, Theron G, Cotton M, Cohn J, Glebe D, et al. Mother-to-child transmission of hepatitis B virus in sub-Saharan Africa: time to act. Lancet Global Health. 2015;3(7):e358–9.CrossRefPubMed Andersson MI, Rajbhandari R, Kew MC, Vento S, Preiser W, Hoepelman AIM, Theron G, Cotton M, Cohn J, Glebe D, et al. Mother-to-child transmission of hepatitis B virus in sub-Saharan Africa: time to act. Lancet Global Health. 2015;3(7):e358–9.CrossRefPubMed
26.
go back to reference Wang Q, Luan W, Warren L, Fiel MI, Blank S, Kadri H, Tuvin D, Hiotis SP. Serum hepatitis B surface antigen correlates with tissue covalently closed circular DNA in patients with hepatitis B-associated hepatocellular carcinoma. J Med Virol. 2016;88(2):244–51.CrossRefPubMed Wang Q, Luan W, Warren L, Fiel MI, Blank S, Kadri H, Tuvin D, Hiotis SP. Serum hepatitis B surface antigen correlates with tissue covalently closed circular DNA in patients with hepatitis B-associated hepatocellular carcinoma. J Med Virol. 2016;88(2):244–51.CrossRefPubMed
27.
go back to reference Kouanfack C, Aghokeng AF, Mondain AM, Bourgeois A, Kenfack A, Mpoudi-Ngole E, Ducos J, Delaporte E, Laurent C. Lamivudine-resistant HBV infection in HIV-positive patients receiving antiretroviral therapy in a public routine clinic in Cameroon. Antivir Ther. 2012;17(2):321–6.CrossRefPubMed Kouanfack C, Aghokeng AF, Mondain AM, Bourgeois A, Kenfack A, Mpoudi-Ngole E, Ducos J, Delaporte E, Laurent C. Lamivudine-resistant HBV infection in HIV-positive patients receiving antiretroviral therapy in a public routine clinic in Cameroon. Antivir Ther. 2012;17(2):321–6.CrossRefPubMed
28.
go back to reference Hubschen JM, Mbah PO, Forbi JC, Otegbayo JA, Olinger CM, Charpentier E, Muller CP. Detection of a new subgenotype of hepatitis B virus genotype A in Cameroon but not in neighbouring Nigeria. Clin Microbiol Infect. 2011;17(1):88–94.CrossRefPubMed Hubschen JM, Mbah PO, Forbi JC, Otegbayo JA, Olinger CM, Charpentier E, Muller CP. Detection of a new subgenotype of hepatitis B virus genotype A in Cameroon but not in neighbouring Nigeria. Clin Microbiol Infect. 2011;17(1):88–94.CrossRefPubMed
29.
go back to reference Kramvis A, Kew MC. Epidemiology of hepatitis B virus in Africa, its genotypes and clinical associations of genotypes. Hepatol Res. 2007;37(s1):S9–S19.CrossRefPubMed Kramvis A, Kew MC. Epidemiology of hepatitis B virus in Africa, its genotypes and clinical associations of genotypes. Hepatol Res. 2007;37(s1):S9–S19.CrossRefPubMed
30.
go back to reference Tufon KA, Meriki HD, Anong DN, Mbunkah HA, Nkuo-Akenji T. Genetic diversity, viraemic and aminotransferases levels in chronic infected hepatitis B patients from Cameroon. BMC Res Notes. 2016;9(1):1–7.CrossRef Tufon KA, Meriki HD, Anong DN, Mbunkah HA, Nkuo-Akenji T. Genetic diversity, viraemic and aminotransferases levels in chronic infected hepatitis B patients from Cameroon. BMC Res Notes. 2016;9(1):1–7.CrossRef
31.
go back to reference Yousif M, Mudawi H, Hussein W, Mukhtar M, Nemeri O, Glebe D, Kramvis A. Genotyping and virological characteristics of hepatitis B virus in HIV-infected individuals in Sudan. Int J Infect Dis. 2014;29:125–32.CrossRefPubMed Yousif M, Mudawi H, Hussein W, Mukhtar M, Nemeri O, Glebe D, Kramvis A. Genotyping and virological characteristics of hepatitis B virus in HIV-infected individuals in Sudan. Int J Infect Dis. 2014;29:125–32.CrossRefPubMed
32.
go back to reference Ma Q, Wang Y. Comprehensive analysis of the prevalence of hepatitis B virus escape mutations in the major hydrophilic region of surface antigen. J Med Virol. 2012;84(2):198–206.CrossRefPubMed Ma Q, Wang Y. Comprehensive analysis of the prevalence of hepatitis B virus escape mutations in the major hydrophilic region of surface antigen. J Med Virol. 2012;84(2):198–206.CrossRefPubMed
33.
go back to reference Scheiblauer H, Soboll H, Nick S. Evaluation of 17 CE-marked HBsAg assays with respect to clinical sensitivity, analytical sensitivity, and hepatitis B virus mutant detection. J Med Virol. 2006;78 Suppl 1:S66–70.CrossRefPubMed Scheiblauer H, Soboll H, Nick S. Evaluation of 17 CE-marked HBsAg assays with respect to clinical sensitivity, analytical sensitivity, and hepatitis B virus mutant detection. J Med Virol. 2006;78 Suppl 1:S66–70.CrossRefPubMed
35.
go back to reference Shaw T, Bartholomeusz A, Locarnini S. HBV drug resistance: mechanisms, detection and interpretation. J Hepatol. 2006;44(3):593–606.CrossRefPubMed Shaw T, Bartholomeusz A, Locarnini S. HBV drug resistance: mechanisms, detection and interpretation. J Hepatol. 2006;44(3):593–606.CrossRefPubMed
36.
go back to reference Delaney WE, Yang H, Westland CE, Das K, Arnold E, Gibbs CS, Miller MD, Xiong S. The hepatitis B virus polymerase mutation rtV173L is selected during lamivudine therapy and enhances viral replication in vitro. J Virol. 2003;77(21):11833–41.CrossRefPubMedPubMedCentral Delaney WE, Yang H, Westland CE, Das K, Arnold E, Gibbs CS, Miller MD, Xiong S. The hepatitis B virus polymerase mutation rtV173L is selected during lamivudine therapy and enhances viral replication in vitro. J Virol. 2003;77(21):11833–41.CrossRefPubMedPubMedCentral
37.
go back to reference Alvarado-Esquivel C, de la Ascension C-GM, Conde-Gonzalez CJ, Juarez-Figueroa L, Ruiz-Maya L, Aguilar-Benavides S, Torres-Valenzuela A, Sablon E. Genotypic resistance to lamivudine among hepatitis B virus isolates in Mexico. J Antimicrob Chemother. 2006;57(2):221–3.CrossRefPubMed Alvarado-Esquivel C, de la Ascension C-GM, Conde-Gonzalez CJ, Juarez-Figueroa L, Ruiz-Maya L, Aguilar-Benavides S, Torres-Valenzuela A, Sablon E. Genotypic resistance to lamivudine among hepatitis B virus isolates in Mexico. J Antimicrob Chemother. 2006;57(2):221–3.CrossRefPubMed
38.
go back to reference Leon P, Pozo F, Echevarria JM. Detection of hepatitis B virus variants resistant to lamivudine and famciclovir among randomly selected chronic carriers from Spain. Enferm Infecc Microbiol Clin. 2004;22(3):133–7.CrossRefPubMed Leon P, Pozo F, Echevarria JM. Detection of hepatitis B virus variants resistant to lamivudine and famciclovir among randomly selected chronic carriers from Spain. Enferm Infecc Microbiol Clin. 2004;22(3):133–7.CrossRefPubMed
Metadata
Title
Serologic and genotypic characterization of hepatitis B virus in HIV-1 infected patients from South West and Littoral Regions of Cameroon
Authors
Tshifhiwa Magoro
George Gachara
Lufuno Mavhandu
Emmaculate Lum
Helen K. Kimbi
Roland N. Ndip
Pascal Bessong
Publication date
01-12-2016
Publisher
BioMed Central
Published in
Virology Journal / Issue 1/2016
Electronic ISSN: 1743-422X
DOI
https://doi.org/10.1186/s12985-016-0636-x

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