OCCULT HEPATITIS B VIRUS INFECTION AND ASSOCIATED GENOTYPES AMONG HBSAG-NEGATIVE SUBJECTS IN BURKINA FASO
Main Article Content
Keywords
HBV, HCV
Abstract
Background: Occult Hepatitis B virus infection (OBI), is characterized by the absence of detectable HBsAg in the blood of a person assumed to be healthy. It remains a potential transmission threat and risk to HBV chronic infection. The purpose of this study was to determine the OBI prevalence among HBsAg negative subjects and to characterize associated genotypes.
Methods: Blood samples of 219 HBsAg-negative subjects tested by ELISA were collected. HBV DNA was investigated in all samples. Viral loads were determined using quantitative real-time PCR. All samples were screened for HBV markers (anti-HBc, anti-HBe, HBsAg). The Pre-S/S region of the HBV genome was sequenced. The database was analyzed using the SPSS and Epi info softwares. Phylogenetic analysis was performed using the BioEdit and MEGA softwares.
Results: Of the 219 samples, 20.1 % were anti-HBc positive, 1.8 % HBeAg and 22.8 % were anti-HBe positive. Fifty-six 56 (25.6 %) of the samples had a detectable HBV DNA and viral loads ranging from 4 IU/mL to 13.6 106 IU/mL. Sixteen of them (16/56) had a viral load < 200 IU/mL, resulting in an OBI prevalence of 7.3 % (16/219) in our study. The remaining 40 subjects had viral loads ? 200 IU/mL, resulting in a “false OBI” prevalence of 18.3% (40/219). HBV genotype E was predominant followed by the quasi-sub-genotype A3. A single "false OBI" strain had the characteristic mutation G145R. Other mutations were observed and all located in the major hydrophilic region (MHR) of the S gene.
Conclusion: The study reported a prevalence of 7.3% of occult hepatitis B infection. It confirms the predominance of genotype E and the existence of a subgroup of quasi-sub-genotype A3 of HBV in Burkina Faso. It further provides information on the existence of “false OBI “. This study has found mutations in the major hydrophilic region (MHR) of the pre-S/S gene of HBV.
Key words: HBV, OBI, Genotypes, Real-time PCR, Sequencing
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References
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[34] Bremer CM, Saniewski M, Wend UC, Torres P, Lelie N, Gerlich WH. Glebe D. Transient occult hepatitis B virus infection in a blood donor with high viremia. Transfusion. 2009, 49(8):1621-1629.
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[39] Hsu CW. Yeh CT. Emergence of hepatitis B virus S gene mutants in patients experiencing hepatitis B surface antigen seroconversion after peginterferon therapy. Hepatology. 2011, 54(1):101-108.
[40] Huang CH, Yuan Q, Chen PJ, Zhang YL, Chen CR, Zheng QB, Yeh SH, Yu H, Xue Y, Chen YX, Liu PG, Ge SX, Zhang J. Xia NS. Influence of mutations in hepatitis B virus surface protein on viral antigenicity and phenotype in occult HBV strains from blood donors. J Hepatol. 2012, 57(4):720-729.
[41] Kalinina T, Iwanski A, Will H. Sterneck M. Deficiency in virion secretion and decreased stability of the hepatitis B virus immune escape mutant G145R. Hepatology. 2003, 38(5):1274-1281.
[42] Norder H, Courouce AM. Magnius LO. Molecular basis of hepatitis B virus serotype variations within the four major subtypes. J Gen Virol. 1992, 73 ( Pt 12):3141-3145.
[43] Seeger C. Mason WS. Hepatitis B virus biology. Microbiol Mol Biol Rev. 2000, 64(1):51-68.
[44] Tian Y, Xu Y, Zhang Z, Meng Z, Qin L, Lu M. Yang D. The amino Acid residues at positions 120 to 123 are crucial for the antigenicity of hepatitis B surface antigen. J Clin Microbiol. 2007, 45(9):2971-2978.
[2] Burnett RJ, Francois G, Kew MC, Leroux-Roels G, Meheus A, Hoosen AA. Mphahlele MJ. Hepatitis B virus and human immunodeficiency virus co-infection in sub-Saharan Africa: a call for further investigation. Liver Int. 2005, 25(2):201-213.
[3] Birama. D, Karim. OA, Wendkuuni. DF, Rebeca. CT, OBIRI-YEBOAH. D, Lassina. T, Théophile. SS, Prosper. B, Justine. Y, Virginio. P, Paul. O, Alain. B, . SR. Jacques. S. World Hepatitis Day 2016 in Burkina Faso: Awareness, Screening, Identification of Hepatitis B Markers, HBV/HCV co-infection and vaccination. Hepat Mon. 2017, 17(6):e13789.
[4] Tao I, Compaore TR, Diarra B, Djigma F, Zohoncon TM, Assih M, Ouermi D, Pietra V, Karou SD. Simpore J. Seroepidemiology of hepatitis B and C viruses in the general population of burkina faso. Hepat Res Treat. 2014, 2014:781843.
[5] Collenberg E, Ouedraogo T, Ganame J, Fickenscher H, Kynast-Wolf G, Becher H, Kouyate B, Krausslich HG, Sangare L. Tebit DM. Seroprevalence of six different viruses among pregnant women and blood donors in rural and urban Burkina Faso: A comparative analysis. J Med Virol. 2006, 78(5):683-692.
[6] Tao I, Bisseye C, Nagalo BM, Sanou M, Kiba A, Surat G, Compaore TR, Traore L, Nikiema JB, Pietra V, Zongo JD. Simpore J. Screening of Hepatitis G and Epstein-Barr Viruses Among Voluntary non Remunerated Blood Donors (VNRBD) in Burkina Faso, West Africa. Mediterr J Hematol Infect Dis. 2013, 5(1):e2013053.
[7] Simpore J, Granato M, Santarelli R, Nsme RA, Coluzzi M, Pietra V, Pignatelli S, Bere A, Faggioni A. Angeloni A. Prevalence of infection by HHV-8, HIV, HCV and HBV among pregnant women in Burkina Faso. J Clin Virol. 2004, 31(1):78-80.
[8] Simpore J, Savadogo A, Ilboudo D, Nadambega MC, Esposito M, Yara J, Pignatelli S, Pietra V. Musumeci S. Toxoplasma gondii, HCV, and HBV seroprevalence and co-infection among HIV-positive and -negative pregnant women in Burkina Faso. J Med Virol. 2006, 78(6):730-733.
[9] Raimondo G, Allain JP, Brunetto MR, Buendia MA, Chen DS, Colombo M, Craxi A, Donato F, Ferrari C, Gaeta GB, Gerlich WH, Levrero M, Locarnini S, Michalak T, Mondelli MU, Pawlotsky JM, Pollicino T, Prati D, Puoti M, Samuel D, Shouval D, Smedile A, Squadrito G, Trepo C, Villa E, Will H, Zanetti AR. Zoulim F. Statements from the Taormina expert meeting on occult hepatitis B virus infection. J Hepatol. 2008, 49(4):652-657.
[10] Said ZN. An overview of occult hepatitis B virus infection. World J Gastroenterol. 2011, 17(15):1927-1938.
[11] Castillo I, Rodriguez-Inigo E, Lopez-Alcorocho JM, Bartolome J, Pardo M. Carreno V. Comparative study on the clinical and virological characteristics among patients with single occult hepatitis B virus (HBV), single occult hepatitis C virus (HCV) and occult HBV and HCV dual infection. J Med Virol. 2007, 79(3):236-241.
[12] Chemin I, Zoulim F, Merle P, Arkhis A, Chevallier M, Kay A, Cova L, Chevallier P, Mandrand B. Trepo C. High incidence of hepatitis B infections among chronic hepatitis cases of unknown aetiology. J Hepatol. 2001, 34(3):447-454.
[13] Candotti D, Diarra B, Bisseye C, Tao I, Pham Quang K, Sanou M, Laperche S, Sanogo R, Allain JP. Simpore J. Molecular characterization of hepatitis B virus in blood donors from Burkina Faso: Prevalence of quasi-subgenotype A3, genotype E, and mixed infections. J Med Virol. 2016, 88(12):2145-2156.
[14] Tatematsu K, Tanaka Y, Kurbanov F, Sugauchi F, Mano S, Maeshiro T, Nakayoshi T, Wakuta M, Miyakawa Y. Mizokami M. A genetic variant of hepatitis B virus divergent from known human and ape genotypes isolated from a Japanese patient and provisionally assigned to new genotype J. J Virol. 2009, 83(20):10538-10547.
[15] Ghosh S, Banerjee P, Deny P, Mondal RK, Nandi M, Roychoudhury A, Das K, Banerjee S, Santra A, Zoulim F, Chowdhury A. Datta S. New HBV subgenotype D9, a novel D/C recombinant, identified in patients with chronic HBeAg-negative infection in Eastern India. J Viral Hepat. 2013, 20(3):209-218.
[16] Lu JJ, Chen EQ, Yang JH, Zhou TY, Liu L. Tang H. A mutation in the interferon regulatory element of HBV may influence the response of interferon treatment in chronic hepatitis B patients. Virol J. 2012, 9:10.
[17] Somda KS, Sermé AK, Coulibaly A, Cissé K, Sawadogo A, Sombié AR. Bougouma A. Hepatitis B Surface Antigen Should Not Be the Only Sought Marker to Distinguish Blood Donors towards Hepatitis B Virus Infection in High Prevalence Area. Open Journal of Gastroenterology. 2016, 6:200-210.
[18] Chen CH, Hung CH, Lee CM, Hu TH, Wang JH, Wang JC, Lu SN. Changchien CS. Pre-S deletion and complex mutations of hepatitis B virus related to advanced liver disease in HBeAg-negative patients. Gastroenterology. 2007, 133(5):1466-1474.
[19] Antar W, El-Shokry MH, Abd El Hamid WA. Helmy MF. Significance of detecting anti-HBc among Egyptian male blood donors negative for HBsAg. Transfus Med. 2010, 20(6):409-413.
[20] Said ZN, Sayed MH, Salama, II, Aboel-Magd EK, Mahmoud MH, Setouhy ME, Mouftah F, Azzab MB, Goubran H, Bassili A. Esmat GE. Occult hepatitis B virus infection among Egyptian blood donors. World J Hepatol. 2013, 5(2):64-73.
[21] Mudawi H, Hussein W, Mukhtar M, Yousif M, Nemeri O, Glebe D. Kramvis A. Overt and occult hepatitis B virus infection in adult Sudanese HIV patients. Int J Infect Dis. 2014, 29:65-70.
[22] N'Dri-Yoman T, Anglaret X, Messou E, Attia A, Polneau S, Toni T, Chenal H, Seyler C, Gabillard D, Wakasugi N, Eholie S. Danel C. Occult HBV infection in untreated HIV-infected adults in Cote d'Ivoire. Antivir Ther. 2010, 15(7):1029-1034.
[23] Nna E, Mbamalu C. Ekejindu I. Occult hepatitis B viral infection among blood donors in South-Eastern Nigeria. Pathog Glob Health. 2014, 108(5):223-228.
[24] Gutierrez-Garcia ML, Fernandez-Rodriguez CM, Lledo-Navarro JL. Buhigas-Garcia I. Prevalence of occult hepatitis B virus infection. World J Gastroenterol. 2011, 17(12):1538-1542.
[25] Yuen MF, Lee CK, Wong DK, Fung J, Hung I, Hsu A, But DY, Cheung TK, Chan P, Yuen JC, Fung FK, Seto WK, Lin CK. Lai CL. Prevalence of occult hepatitis B infection in a highly endemic area for chronic hepatitis B: a study of a large blood donor population. Gut. 2010, 59(10):1389-1393.
[26] Ireland JH, O'Donnell B, Basuni AA, Kean JD, Wallace LA, Lau GK. Carman WF. Reactivity of 13 in vitro expressed hepatitis B surface antigen variants in 7 commercial diagnostic assays. Hepatology. 2000, 31(5):1176-1182.
[27] Weber B. Diagnostic impact of the genetic variability of the hepatitis B virus surface antigen gene. J Med Virol. 2006, 78 Suppl 1:S59-65.
[28] Zhu HL, Li X, Li J. Zhang ZH. Genetic variation of occult hepatitis B virus infection. World J Gastroenterol. 2016, 22(13):3531-3546.
[29] Brechot C, Thiers V, Kremsdorf D, Nalpas B, Pol S. Paterlini-Brechot P. Persistent hepatitis B virus infection in subjects without hepatitis B surface antigen: clinically significant or purely "occult"? Hepatology. 2001, 34(1):194-203.
[30] Vivekanandan P, Kannangai R, Ray SC, Thomas DL. Torbenson M. Comprehensive genetic and epigenetic analysis of occult hepatitis B from liver tissue samples. Clin Infect Dis. 2008, 46(8):1227-1236.
[31] Blum HE, Galun E, Liang TJ, von Weizsacker F. Wands JR. Naturally occurring missense mutation in the polymerase gene terminating hepatitis B virus replication. J Virol. 1991, 65(4):1836-1842.
[32] Chaudhuri V, Tayal R, Nayak B, Acharya SK. Panda SK. Occult hepatitis B virus infection in chronic liver disease: full-length genome and analysis of mutant surface promoter. Gastroenterology. 2004, 127(5):1356-1371.
[33] Brechot C. Pathogenesis of hepatitis B virus-related hepatocellular carcinoma: old and new paradigms. Gastroenterology. 2004, 127(5 Suppl 1):S56-61.
[34] Bremer CM, Saniewski M, Wend UC, Torres P, Lelie N, Gerlich WH. Glebe D. Transient occult hepatitis B virus infection in a blood donor with high viremia. Transfusion. 2009, 49(8):1621-1629.
[35] Candotti D, Lin CK, Belkhiri D, Sakuldamrongpanich T, Biswas S, Lin S, Teo D, Ayob Y. Allain JP. Occult hepatitis B infection in blood donors from South East Asia: molecular characterisation and potential mechanisms of occurrence. Gut. 2012, 61(12):1744-1753.
[36] Mulders MN, Venard V, Njayou M, Edorh AP, Bola Oyefolu AO, Kehinde MO, Muyembe Tamfum JJ, Nebie YK, Maiga I, Ammerlaan W, Fack F, Omilabu SA, Le Faou A. Muller CP. Low genetic diversity despite hyperendemicity of hepatitis B virus genotype E throughout West Africa. J Infect Dis. 2004, 190(2):400-408.
[37] Kurbanov F, Tanaka Y, Fujiwara K, Sugauchi F, Mbanya D, Zekeng L, Ndembi N, Ngansop C, Kaptue L, Miura T, Ido E, Hayami M, Ichimura H. Mizokami M. A new subtype (subgenotype) Ac (A3) of hepatitis B virus and recombination between genotypes A and E in Cameroon. J Gen Virol. 2005, 86(Pt 7):2047-2056.
[38] Makuwa M, Souquiere S, Telfer P, Apetrei C, Vray M, Bedjabaga I, Mouinga-Ondeme A, Onanga R, Marx PA, Kazanji M, Roques P. Simon F. Identification of hepatitis B virus subgenotype A3 in rural Gabon. J Med Virol. 2006, 78(9):1175-1184.
[39] Hsu CW. Yeh CT. Emergence of hepatitis B virus S gene mutants in patients experiencing hepatitis B surface antigen seroconversion after peginterferon therapy. Hepatology. 2011, 54(1):101-108.
[40] Huang CH, Yuan Q, Chen PJ, Zhang YL, Chen CR, Zheng QB, Yeh SH, Yu H, Xue Y, Chen YX, Liu PG, Ge SX, Zhang J. Xia NS. Influence of mutations in hepatitis B virus surface protein on viral antigenicity and phenotype in occult HBV strains from blood donors. J Hepatol. 2012, 57(4):720-729.
[41] Kalinina T, Iwanski A, Will H. Sterneck M. Deficiency in virion secretion and decreased stability of the hepatitis B virus immune escape mutant G145R. Hepatology. 2003, 38(5):1274-1281.
[42] Norder H, Courouce AM. Magnius LO. Molecular basis of hepatitis B virus serotype variations within the four major subtypes. J Gen Virol. 1992, 73 ( Pt 12):3141-3145.
[43] Seeger C. Mason WS. Hepatitis B virus biology. Microbiol Mol Biol Rev. 2000, 64(1):51-68.
[44] Tian Y, Xu Y, Zhang Z, Meng Z, Qin L, Lu M. Yang D. The amino Acid residues at positions 120 to 123 are crucial for the antigenicity of hepatitis B surface antigen. J Clin Microbiol. 2007, 45(9):2971-2978.