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Published in: BMC Infectious Diseases 1/2017

Open Access 01-12-2017 | Research article

Hepatitis B virus strains from Rwandan blood donors are genetically similar and form one clade within subgenotype A1

Authors: Theogene Twagirumugabe, Gatare Swaibu, Timothy David Walker, Magnus Lindh, Jean Bosco Gahutu, Tomas Bergström, Heléne Norder

Published in: BMC Infectious Diseases | Issue 1/2017

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Abstract

Background

Rwanda is a central African country with about 12 million inhabitants. The 1994 genocide against the Tutsi destroyed much of the infrastructure, including the health system. Although this has improved significantly, many challenges remain to be addressed. In this study, the prevalence of serological markers of past and ongoing hepatitis B virus (HBV) infection and HBV vaccine related immunity was investigated in samples from blood donors from all regions of Rwanda.

Methods

The results from hepatitis B surface antigen (HBsAg) analyses of all (45,061) blood donations collected countrywide in 2014 from 13,637 first time and 31,424 repeat blood donors were compiled. Samples from 581 HBsAg negative blood donors were selected for further analysis for antibodies against HBV, anti-HBs and anti-HBc. Additional 139 samples from HBsAg positive donors were analyzed for HBeAg/anti-HBe (132 samples) and for HBV DNA. The S-gene was amplified by PCR, products sequenced, and phylogenetic analysis was performed.

Results

HBsAg was found in 4.1% of first time donors with somewhat higher prevalence among those from the Central and Eastern regions than from other parts of the country. Indications of past infection was found in 21% of the HBsAg negative donors, 4.3% had only anti-HBs suggesting HBV vaccination. HBeAg was detected in 28 (21%), anti-HBe in 97 (73%), and both HBeAg and anti-HBe in 4 of 132 HBsAg positive donors. HBV DNA was found in 85 samples, and the complete S-gene was sequenced in 58 of those. Phylogenetic analysis of the sequences revealed that all HBV strains belonged to subgenotype A1, and formed one clade in the phylogenetic tree. In addition, 12 strains from first time donors had a unique 18 amino acid deletion in the N-terminal part of the pre-S2 region.

Conclusion

This study indicated that the prevalence of hepatitis B is intermediate in Rwanda and that the vaccination coverage is relatively low in young adults. All surveyed Rwandan blood donors were infected with similar subgenotype A1 strains, and a high frequency of those with anti-HBe had detectable HBV DNA. Several strains had in addition a unique pre-S2 deletion, the virulence of which needs to be further studied.
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Literature
1.
go back to reference Tong S, Revill P. Overview of hepatitis B viral replication and genetic variability. J Hepatol. 2016;64 Suppl 1:S4–s16.CrossRefPubMed Tong S, Revill P. Overview of hepatitis B viral replication and genetic variability. J Hepatol. 2016;64 Suppl 1:S4–s16.CrossRefPubMed
2.
go back to reference Wain-Hobson S, Pourcel C, Brechot C, Charnay P, Dubois MF, Fritsch A, et al. Structure and expression of the hepatitis B virus genome. Dev Biol Stand. 1981;50:293–300.PubMed Wain-Hobson S, Pourcel C, Brechot C, Charnay P, Dubois MF, Fritsch A, et al. Structure and expression of the hepatitis B virus genome. Dev Biol Stand. 1981;50:293–300.PubMed
3.
go back to reference Norder H, Courouce AM, Coursaget P, Echevarria JM, Lee SD, Mushahwar IK, et al. Genetic diversity of hepatitis B virus strains derived worldwide: genotypes, subgenotypes, and HBsAg subtypes. Intervirology. 2004;47(6):289–309.CrossRefPubMed Norder H, Courouce AM, Coursaget P, Echevarria JM, Lee SD, Mushahwar IK, et al. Genetic diversity of hepatitis B virus strains derived worldwide: genotypes, subgenotypes, and HBsAg subtypes. Intervirology. 2004;47(6):289–309.CrossRefPubMed
4.
go back to reference Kramvis A, Kew MC. Epidemiology of hepatitis B virus in Africa, its genotypes and clinical associations of genotypes. Hepatol Res: Off J Jpn Soc Hepatol. 2007;37 Suppl 1:S9–S19.CrossRef Kramvis A, Kew MC. Epidemiology of hepatitis B virus in Africa, its genotypes and clinical associations of genotypes. Hepatol Res: Off J Jpn Soc Hepatol. 2007;37 Suppl 1:S9–S19.CrossRef
5.
8.
go back to reference Aspinall EJ, Hawkins G, Fraser A, Hutchinson SJ, Goldberg D. Hepatitis B prevention, diagnosis, treatment and care: a review. Occup Med. 2011;61(8):531–40.CrossRef Aspinall EJ, Hawkins G, Fraser A, Hutchinson SJ, Goldberg D. Hepatitis B prevention, diagnosis, treatment and care: a review. Occup Med. 2011;61(8):531–40.CrossRef
9.
go back to reference Lozano R, Naghavi M, Foreman K, Lim S, Shibuya K, Aboyans V, et al. Global and regional mortality from 235 causes of death for 20 age groups in 1990 and 2010: a systematic analysis for the global burden of disease study 2010. Lancet. 2012;380(9859):2095–128.CrossRefPubMed Lozano R, Naghavi M, Foreman K, Lim S, Shibuya K, Aboyans V, et al. Global and regional mortality from 235 causes of death for 20 age groups in 1990 and 2010: a systematic analysis for the global burden of disease study 2010. Lancet. 2012;380(9859):2095–128.CrossRefPubMed
10.
go back to reference Basnayake SK, Easterbrook PJ. Wide variation in estimates of global prevalence and burden of chronic hepatitis B and C infection cited in published literature. J Viral Hepat. 2016;23(7):545–59.CrossRefPubMed Basnayake SK, Easterbrook PJ. Wide variation in estimates of global prevalence and burden of chronic hepatitis B and C infection cited in published literature. J Viral Hepat. 2016;23(7):545–59.CrossRefPubMed
11.
go back to reference Hoofnagle JH, Dusheiko GM, Seeff LB, Jones EA, Waggoner JG, Bales ZB. Seroconversion from hepatitis B e antigen to antibody in chronic type B hepatitis. Ann Intern Med. 1981;94(6):744–8.CrossRefPubMed Hoofnagle JH, Dusheiko GM, Seeff LB, Jones EA, Waggoner JG, Bales ZB. Seroconversion from hepatitis B e antigen to antibody in chronic type B hepatitis. Ann Intern Med. 1981;94(6):744–8.CrossRefPubMed
12.
go back to reference Carman WF, Jacyna MR, Hadziyannis S, Karayiannis P, McGarvey MJ, Makris A, et al. Mutation preventing formation of hepatitis B e antigen in patients with chronic hepatitis B infection. Lancet. 1989;2(8663):588–91.CrossRefPubMed Carman WF, Jacyna MR, Hadziyannis S, Karayiannis P, McGarvey MJ, Makris A, et al. Mutation preventing formation of hepatitis B e antigen in patients with chronic hepatitis B infection. Lancet. 1989;2(8663):588–91.CrossRefPubMed
13.
go back to reference Funk ML, Rosenberg DM, Lok AS. World-wide epidemiology of HBeAg-negative chronic hepatitis B and associated precore and core promoter variants. J Viral Hepat. 2002;9(1):52–61.CrossRefPubMed Funk ML, Rosenberg DM, Lok AS. World-wide epidemiology of HBeAg-negative chronic hepatitis B and associated precore and core promoter variants. J Viral Hepat. 2002;9(1):52–61.CrossRefPubMed
14.
go back to reference Baqai SF, Proudfoot J, Yi DH, Mangahas M, Gish RG. High rate of core promoter and precore mutations in patients with chronic hepatitis B. Hepatol Int. 2015;9:209–17.CrossRefPubMed Baqai SF, Proudfoot J, Yi DH, Mangahas M, Gish RG. High rate of core promoter and precore mutations in patients with chronic hepatitis B. Hepatol Int. 2015;9:209–17.CrossRefPubMed
15.
go back to reference Bonino F, Rosina F, Rizzetto M, Rizzi R, Chiaberge E, Tardanico R, et al. Chronic hepatitis in HBsAg carriers with serum HBV-DNA and anti-HBe. Gastroenterology. 1986;90(5):1268–73.CrossRefPubMed Bonino F, Rosina F, Rizzetto M, Rizzi R, Chiaberge E, Tardanico R, et al. Chronic hepatitis in HBsAg carriers with serum HBV-DNA and anti-HBe. Gastroenterology. 1986;90(5):1268–73.CrossRefPubMed
16.
go back to reference Hagiwara S, Kudo M, Minami Y, Chung H, Nakatani T, Fukunaga T, et al. Clinical significance of the genotype and core promoter/pre-core mutations in hepatitis B virus carriers. Intervirology. 2006;49(4):200–6.CrossRefPubMed Hagiwara S, Kudo M, Minami Y, Chung H, Nakatani T, Fukunaga T, et al. Clinical significance of the genotype and core promoter/pre-core mutations in hepatitis B virus carriers. Intervirology. 2006;49(4):200–6.CrossRefPubMed
17.
go back to reference Norder H, Arauz-Ruiz P, Blitz L, Pujol FH, Echevarria JM, Magnius LO. The T(1858) variant predisposing to the precore stop mutation correlates with one of two major genotype F hepatitis B virus clades. J Gen Virol. 2003;84(8):2083–7.CrossRefPubMed Norder H, Arauz-Ruiz P, Blitz L, Pujol FH, Echevarria JM, Magnius LO. The T(1858) variant predisposing to the precore stop mutation correlates with one of two major genotype F hepatitis B virus clades. J Gen Virol. 2003;84(8):2083–7.CrossRefPubMed
18.
go back to reference Inoue J, Kondo Y, Umetsu T, Yamamoto T, Miura M, Mano Y, et al. Shifting hepatitis B virus genotypes of acute hepatitis B patients in northeast Japan. J Med Virol. 2016;88(1):69–78.CrossRefPubMed Inoue J, Kondo Y, Umetsu T, Yamamoto T, Miura M, Mano Y, et al. Shifting hepatitis B virus genotypes of acute hepatitis B patients in northeast Japan. J Med Virol. 2016;88(1):69–78.CrossRefPubMed
19.
go back to reference Lindh M, Hannoun C, Dhillon AP, Norkrans G, Horal P. Core promoter mutations and genotypes in relation to viral replication and liver damage in East Asian hepatitis B virus carriers. J Infect Dis. 1999;179(4):775–82.CrossRefPubMed Lindh M, Hannoun C, Dhillon AP, Norkrans G, Horal P. Core promoter mutations and genotypes in relation to viral replication and liver damage in East Asian hepatitis B virus carriers. J Infect Dis. 1999;179(4):775–82.CrossRefPubMed
20.
go back to reference Sato S, Suzuki K, Akahane Y, Akamatsu K, Akiyama K, Yunomura K, et al. Hepatitis B virus strains with mutations in the core promoter in patients with fulminant hepatitis. Ann Intern Med. 1995;122(4):241–8.CrossRefPubMed Sato S, Suzuki K, Akahane Y, Akamatsu K, Akiyama K, Yunomura K, et al. Hepatitis B virus strains with mutations in the core promoter in patients with fulminant hepatitis. Ann Intern Med. 1995;122(4):241–8.CrossRefPubMed
21.
go back to reference Liang TJ, Block TM, McMahon BJ, Ghany MG, Urban S, Guo JT, et al. Present and future therapies of hepatitis B: from discovery to cure. Hepatology. 2015;62(6):1893–908.CrossRefPubMedPubMedCentral Liang TJ, Block TM, McMahon BJ, Ghany MG, Urban S, Guo JT, et al. Present and future therapies of hepatitis B: from discovery to cure. Hepatology. 2015;62(6):1893–908.CrossRefPubMedPubMedCentral
22.
go back to reference Su WJ, Liu CC, Liu DP, Chen SF, Huang JJ, Chan TC, et al. Effect of age on the incidence of acute hepatitis B after 25 years of a universal newborn hepatitis B immunization program in Taiwan. J Infect Dis. 2012;205(5):757–62.CrossRefPubMed Su WJ, Liu CC, Liu DP, Chen SF, Huang JJ, Chan TC, et al. Effect of age on the incidence of acute hepatitis B after 25 years of a universal newborn hepatitis B immunization program in Taiwan. J Infect Dis. 2012;205(5):757–62.CrossRefPubMed
23.
go back to reference Ott JJ, Stevens GA, Groeger J, Wiersma ST. Global epidemiology of hepatitis B virus infection: new estimates of age-specific HBsAg seroprevalence and endemicity. Vaccine. 2012;30(12):2212–9.CrossRefPubMed Ott JJ, Stevens GA, Groeger J, Wiersma ST. Global epidemiology of hepatitis B virus infection: new estimates of age-specific HBsAg seroprevalence and endemicity. Vaccine. 2012;30(12):2212–9.CrossRefPubMed
24.
go back to reference Kateera F, Walker TD, Mutesa L, Mutabazi V, Musabeyesu E, Mukabatsinda C, et al. Hepatitis B and C seroprevalence among health care workers in a tertiary hospital in Rwanda. Trans R Soc Trop Med Hyg. 2015;109(3):203–8.CrossRefPubMedPubMedCentral Kateera F, Walker TD, Mutesa L, Mutabazi V, Musabeyesu E, Mukabatsinda C, et al. Hepatitis B and C seroprevalence among health care workers in a tertiary hospital in Rwanda. Trans R Soc Trop Med Hyg. 2015;109(3):203–8.CrossRefPubMedPubMedCentral
25.
go back to reference Pirillo MF, Bassani L, Germinario EA, Mancini MG, Vyankandondera J, Okong P, et al. Seroprevalence of hepatitis B and C viruses among HIV-infected pregnant women in Uganda and Rwanda. J Med Virol. 2007;79(12):1797–801.CrossRefPubMed Pirillo MF, Bassani L, Germinario EA, Mancini MG, Vyankandondera J, Okong P, et al. Seroprevalence of hepatitis B and C viruses among HIV-infected pregnant women in Uganda and Rwanda. J Med Virol. 2007;79(12):1797–801.CrossRefPubMed
26.
go back to reference Rusine J, Ondoa P, Asiimwe-Kateera B, Boer KR, Uwimana JM, Mukabayire O, et al. High seroprevalence of HBV and HCV infection in HIV-infected adults in Kigali, Rwanda. PLoS One. 2013;8(5):e63303.CrossRefPubMedPubMedCentral Rusine J, Ondoa P, Asiimwe-Kateera B, Boer KR, Uwimana JM, Mukabayire O, et al. High seroprevalence of HBV and HCV infection in HIV-infected adults in Kigali, Rwanda. PLoS One. 2013;8(5):e63303.CrossRefPubMedPubMedCentral
27.
go back to reference Franco E, Bagnato B, Marino MG, Meleleo C, Serino L, Zaratti L. Hepatitis B: epidemiology and prevention in developing countries. World J Hepatol. 2012;4(3):74–80.CrossRefPubMedPubMedCentral Franco E, Bagnato B, Marino MG, Meleleo C, Serino L, Zaratti L. Hepatitis B: epidemiology and prevention in developing countries. World J Hepatol. 2012;4(3):74–80.CrossRefPubMedPubMedCentral
28.
go back to reference Norder H, Hammas B, Lee SD, Bile K, Courouce AM, Mushahwar IK, et al. Genetic relatedness of hepatitis B viral strains of diverse geographical origin and natural variations in the primary structure of the surface antigen. J Gen Virol. 1993;74(7):1341–8.CrossRefPubMed Norder H, Hammas B, Lee SD, Bile K, Courouce AM, Mushahwar IK, et al. Genetic relatedness of hepatitis B viral strains of diverse geographical origin and natural variations in the primary structure of the surface antigen. J Gen Virol. 1993;74(7):1341–8.CrossRefPubMed
29.
go back to reference Amponsah-Dacosta E, Lebelo RL, Rakgole JN, Selabe SG, Gededzha MP, Mayaphi SH, et al. Hepatitis B virus infection in post-vaccination South Africa: occult HBV infection and circulating surface gene variants. J Clin Virol. 2015;63:12–7.CrossRefPubMed Amponsah-Dacosta E, Lebelo RL, Rakgole JN, Selabe SG, Gededzha MP, Mayaphi SH, et al. Hepatitis B virus infection in post-vaccination South Africa: occult HBV infection and circulating surface gene variants. J Clin Virol. 2015;63:12–7.CrossRefPubMed
31.
go back to reference Hubschen JM, Mugabo J, Peltier CA, Karasi JC, Sausy A, Kirpach P, et al. Exceptional genetic variability of hepatitis B virus indicates that Rwanda is east of an emerging African genotype E/A1 divide. J Med Virol. 2009;81(3):435–40.CrossRefPubMed Hubschen JM, Mugabo J, Peltier CA, Karasi JC, Sausy A, Kirpach P, et al. Exceptional genetic variability of hepatitis B virus indicates that Rwanda is east of an emerging African genotype E/A1 divide. J Med Virol. 2009;81(3):435–40.CrossRefPubMed
32.
go back to reference Ochwoto M, Chauhan R, Gopalakrishnan D, Chen CY, Ng’ang’a Z, Okoth F, et al. Genotyping and molecular characterization of hepatitis B virus in liver disease patients in Kenya. Infect Genet Evol. 2013;20:103–10.CrossRefPubMed Ochwoto M, Chauhan R, Gopalakrishnan D, Chen CY, Ng’ang’a Z, Okoth F, et al. Genotyping and molecular characterization of hepatitis B virus in liver disease patients in Kenya. Infect Genet Evol. 2013;20:103–10.CrossRefPubMed
33.
go back to reference Chen CH, Changchien CS, Lee CM, Hung CH, Hu TH, Wang JH, et al. Combined mutations in pre-s/surface and core promoter/precore regions of hepatitis B virus increase the risk of hepatocellular carcinoma: a case-control study. J Infect Dis. 2008;198(11):1634–42.CrossRefPubMed Chen CH, Changchien CS, Lee CM, Hung CH, Hu TH, Wang JH, et al. Combined mutations in pre-s/surface and core promoter/precore regions of hepatitis B virus increase the risk of hepatocellular carcinoma: a case-control study. J Infect Dis. 2008;198(11):1634–42.CrossRefPubMed
34.
go back to reference Preikschat P, Gunther S, Reinhold S, Will H, Budde K, Neumayer HH, et al. Complex HBV populations with mutations in core promoter, C gene, and pre-S region are associated with development of cirrhosis in long-term renal transplant recipients. Hepatology. 2002;35(2):466–77.CrossRefPubMed Preikschat P, Gunther S, Reinhold S, Will H, Budde K, Neumayer HH, et al. Complex HBV populations with mutations in core promoter, C gene, and pre-S region are associated with development of cirrhosis in long-term renal transplant recipients. Hepatology. 2002;35(2):466–77.CrossRefPubMed
35.
go back to reference Fang ZL, Sabin CA, Dong BQ, Wei SC, Chen QY, Fang KX, et al. Hepatitis B virus pre-S deletion mutations are a risk factor for hepatocellular carcinoma: a matched nested case-control study. J Gen Virol. 2008;89(11):2882–90.CrossRefPubMedPubMedCentral Fang ZL, Sabin CA, Dong BQ, Wei SC, Chen QY, Fang KX, et al. Hepatitis B virus pre-S deletion mutations are a risk factor for hepatocellular carcinoma: a matched nested case-control study. J Gen Virol. 2008;89(11):2882–90.CrossRefPubMedPubMedCentral
36.
go back to reference Huy TT, Ushijima H, Win KM, Luengrojanakul P, Shrestha PK, Zhong ZH, et al. High prevalence of hepatitis B virus pre-s mutant in countries where it is endemic and its relationship with genotype and chronicity. J Clin Microbiol. 2003;41(12):5449–55.CrossRefPubMedPubMedCentral Huy TT, Ushijima H, Win KM, Luengrojanakul P, Shrestha PK, Zhong ZH, et al. High prevalence of hepatitis B virus pre-s mutant in countries where it is endemic and its relationship with genotype and chronicity. J Clin Microbiol. 2003;41(12):5449–55.CrossRefPubMedPubMedCentral
37.
go back to reference Grandjacques C, Pradat P, Stuyver L, Chevallier M, Chevallier P, Pichoud C, et al. Rapid detection of genotypes and mutations in the pre-core promoter and the pre-core region of hepatitis B virus genome: correlation with viral persistence and disease severity. J Hepatol. 2000;33(3):430–9.CrossRefPubMed Grandjacques C, Pradat P, Stuyver L, Chevallier M, Chevallier P, Pichoud C, et al. Rapid detection of genotypes and mutations in the pre-core promoter and the pre-core region of hepatitis B virus genome: correlation with viral persistence and disease severity. J Hepatol. 2000;33(3):430–9.CrossRefPubMed
38.
go back to reference Dupinay T, Restorp K, Leutscher P, Rousset D, Chemin I, Migliani R, et al. High prevalence of hepatitis B virus genotype E in Northern Madagascar indicates a West-African lineage. J Med Virol. 2010;82(9):1515–26.CrossRefPubMed Dupinay T, Restorp K, Leutscher P, Rousset D, Chemin I, Migliani R, et al. High prevalence of hepatitis B virus genotype E in Northern Madagascar indicates a West-African lineage. J Med Virol. 2010;82(9):1515–26.CrossRefPubMed
39.
go back to reference Fagan EA, Smith PM, Davison F, Williams R. Fulminant hepatitis B in successive female sexual partners of two anti-HBe-positive males. Lancet (Lond Engl). 1986;2(8506):538–40.CrossRef Fagan EA, Smith PM, Davison F, Williams R. Fulminant hepatitis B in successive female sexual partners of two anti-HBe-positive males. Lancet (Lond Engl). 1986;2(8506):538–40.CrossRef
40.
go back to reference Oren I, Hershow RC, Ben-Porath E, Krivoy N, Goldstein N, Rishpon S, et al. A common-source outbreak of fulminant hepatitis B in a hospital. Ann Intern Med. 1989;110(9):691–8.CrossRefPubMed Oren I, Hershow RC, Ben-Porath E, Krivoy N, Goldstein N, Rishpon S, et al. A common-source outbreak of fulminant hepatitis B in a hospital. Ann Intern Med. 1989;110(9):691–8.CrossRefPubMed
41.
go back to reference Arankalle VA, Gandhi S, Lole KS, Chadha MS, Gupte GM, Lokhande MU. An outbreak of hepatitis B with high mortality in India: association with precore, basal core promoter mutants and improperly sterilized syringes. J Viral Hepat. 2011;18(4):e20–28.CrossRefPubMed Arankalle VA, Gandhi S, Lole KS, Chadha MS, Gupte GM, Lokhande MU. An outbreak of hepatitis B with high mortality in India: association with precore, basal core promoter mutants and improperly sterilized syringes. J Viral Hepat. 2011;18(4):e20–28.CrossRefPubMed
42.
go back to reference Papatheodoridis GV, Hadziyannis SJ. Diagnosis and management of pre-core mutant chronic hepatitis B. J Viral Hepat. 2001;8(5):311–21.CrossRefPubMed Papatheodoridis GV, Hadziyannis SJ. Diagnosis and management of pre-core mutant chronic hepatitis B. J Viral Hepat. 2001;8(5):311–21.CrossRefPubMed
43.
go back to reference Zhong YW, Di FL, Liu C, Zhang XC, Bi JF, Li YL, et al. Hepatitis B virus basal core promoter/precore mutants and association with liver cirrhosis in children with chronic hepatitis B virus infection. Clin Microbiol Infect. 2016;22(4):379. e1–8.CrossRefPubMed Zhong YW, Di FL, Liu C, Zhang XC, Bi JF, Li YL, et al. Hepatitis B virus basal core promoter/precore mutants and association with liver cirrhosis in children with chronic hepatitis B virus infection. Clin Microbiol Infect. 2016;22(4):379. e1–8.CrossRefPubMed
44.
go back to reference Kamijo N, Matsumoto A, Umemura T, Shibata S, Ichikawa Y, Kimura T, et al. Mutations of pre-core and basal core promoter before and after hepatitis B e antigen seroconversion. World J Gastroenterol. 2015;21(2):541–8.CrossRefPubMedPubMedCentral Kamijo N, Matsumoto A, Umemura T, Shibata S, Ichikawa Y, Kimura T, et al. Mutations of pre-core and basal core promoter before and after hepatitis B e antigen seroconversion. World J Gastroenterol. 2015;21(2):541–8.CrossRefPubMedPubMedCentral
45.
go back to reference Tseng TC, Liu CJ, Yang HC, Chen CL, Yang WT, Tsai CS, et al. Higher proportion of viral basal core promoter mutant increases the risk of liver cirrhosis in hepatitis B carriers. Gut. 2015;64(2):292–302.CrossRefPubMed Tseng TC, Liu CJ, Yang HC, Chen CL, Yang WT, Tsai CS, et al. Higher proportion of viral basal core promoter mutant increases the risk of liver cirrhosis in hepatitis B carriers. Gut. 2015;64(2):292–302.CrossRefPubMed
46.
go back to reference Park YM, Jang JW, Yoo SH, Kim SH, Oh IM, Park SJ, et al. Combinations of eight key mutations in the X/preC region and genomic activity of hepatitis B virus are associated with hepatocellular carcinoma. J Viral Hepat. 2014;21(3):171–7.CrossRefPubMed Park YM, Jang JW, Yoo SH, Kim SH, Oh IM, Park SJ, et al. Combinations of eight key mutations in the X/preC region and genomic activity of hepatitis B virus are associated with hepatocellular carcinoma. J Viral Hepat. 2014;21(3):171–7.CrossRefPubMed
Metadata
Title
Hepatitis B virus strains from Rwandan blood donors are genetically similar and form one clade within subgenotype A1
Authors
Theogene Twagirumugabe
Gatare Swaibu
Timothy David Walker
Magnus Lindh
Jean Bosco Gahutu
Tomas Bergström
Heléne Norder
Publication date
01-12-2017
Publisher
BioMed Central
Published in
BMC Infectious Diseases / Issue 1/2017
Electronic ISSN: 1471-2334
DOI
https://doi.org/10.1186/s12879-016-2149-z

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