High Frequency of HBeAg-Negative Cases in Naive HBsAg-Positive Subjects with Chronic Hepatitis B Virus Infection Managed in the Yaoundé Hepatitis Therapeutic Committee: A Cross Sectional Study

Firmin Ankouane^*, Mathurin Kowo, Oudou Njoya, Elie Claude Ndjitoyap Ndam

Department of Internal Medicine and Specialties, Faculty of Medicine and Biomedical Sciences, University of Yaoundé I, Yaoundé, Cameroon.

DOI: 10.4236/ojepi.2015.52015                

Abstract

The aim was to describe the epidemiology of the chronic hepatitis B virus (HBV) infection within Yaoundé Hepatitis Therapeutic Committee. Methods: This was a cross-sectional study from June 2004 to May 2012. We consecutively collected epidemiological data (gender, age, alanine aminotransferase-ALT, HBe-antigen-HBeAg, hepatitis B viral load-HBV-DNA and cirrhosis evaluation) from naive hepatitis B surface antigen (HBsAg)-positive patients with chronic HBV infection. Chronic HBV infection is defined by the persistence of HBsAg for at least six months. The level of serum HBV-DNA was determined by the COBAS-AmpliPrep Technical/COBAS-TaqMan HBV^® 2.0 (Roche). Data were entered and analyzed using SPSS 20.0 software (IBM Corporation, USA). Results: Of the 315 HBsAg-positive patients consulted, 74.6% were male; mean (SD) age 35.04 (10.25) years. Nearly 92% were HBeAg-negative. The serum ALT level was normal in 63.2%; HBV-DNA was detected in 81.0% and was ≤2000 IU/mL in 65.9%. Liver biopsy was performed in 145 (46.03%); 10 (6.9%) had cirrhosis. HBeAg-negative patients were older than HBeAg-positive (35.3 vs. 31.9 years; p = 0.006). The serum ALT level was high in 84.0% HBeAg-positive patients and in 32.8% HBeAg-negative (p < 0.0001). HBV-DNA was detected in 100% of HBeAg-positive patients against 79.7% of HBeAg-negative (p = 0.05). The median HBV-DNA level was 1550 × 103 IU/mL in HBeAg-positive patients and 1140 IU/mL in HBeAg-negative (p < 0.0001). Cirrhosis was diagnosed in 15.4% of HBeAg-positive patients and in 6.1% of HBeAg-negative (p = 0.221). Conclusion: HBeAg-negative cases are predominant among HBsAg-positive patients with chronic HBV infection in Cameroon. With the knowledge of this epidemiology, the care of patients will be improved.

Keywords

Hepatitis B, Hepatitis B e Antigens, Viral Load, Liver Cirrhosis, Cameroon

Conflicts of Interest

The authors declare no conflicts of interest.

References

[1]	World Health Organization (2015) Hepatitis B. Fact Sheet No. 204. http://www.who.int/mediacentre/factsheets/fs204/en/
[2]	Liaw, Y.F., Brunetto, M.R. and Hadziyannis, S.J. (2010) The Natural History of Chronic HBV Infection and Geographical Differences. Antiviral Therapy, 15, 25-33. http://dx.doi.org/10.3851/IMP1621
[3]	Bekku, D., Arai, M., Imazeki, F., Yonemitsu, Y., Kanda, T., Fujiwara, K.F.K., Sato, K., Itoga, S., Nomura, F. and Yokosuka, O. (2011) Long-Term Follow-Up of Patients with Hepatitis B e Antigen Negative Chronic Hepatitis B. Journal of Gastroenterology and Hepatology, 26, 122-128. http://dx.doi.org/10.1111/j.1440-1746.2010.06322.x
[4]	Fonseca, J.C.F. (2007) Natural History of Chronic Hepatitis B [Abstract]. Revista da Sociedade Brasileira de Medicina Tropical, 40, 672-677. http://dx.doi.org/10.1590/S0037-86822007000600015
[5]	Lai, C.L., Ratziu, V., Yuen, M.F. and Poynard, T. (2003) Viral Hepatitis. Lancet, 3, 2089-2094. http://dx.doi.org/10.1016/S0140-6736(03)15108-2
[6]	Hui, C.K. and Lau, G.K. (2007) Treatment of Hepatitis B e Antigen-Negative Patients. Current Treatment Options in Gastroenterology, 10, 474-482. http://dx.doi.org/10.1007/s11938-007-0047-6
[7]	Marcellin, P., Bonino, F., Yurdaydin, C., Hadziyannis, S., Moucari, R., Kapprell, H.P., Rothe, V., Popescu, M. and Brunetto, M.R. (2013) Hepatitis B Surface Antigen Levels: Association with 5-Year Response to Peginterferon Alfa-2a in Hepatitis B e-Antigen-Negative Patients. Hepatology International, 7, 88-97. http://dx.doi.org/10.1007/s12072-012-9343-x
[8]	Manesis, E.K. (2006) HBeAg-Negative Chronic Hepatitis B: From Obscurity to Prominence. Journal of Hepatology, 45, 343-346. http://dx.doi.org/10.1016/j.jhep.2006.07.001
[9]	Funk, M.L., Rosenberg, D.M. and Lok, A.S. (2002) World-Wide Epidemiology of HBeAg-Negative Chronic Hepatitis B and Associated Precore and Core Promoter Variants. Journal of Viral Hepatitis, 9, 52-61. http://dx.doi.org/10.1046/j.1365-2893.2002.00304.x
[10]	Chan, H.L.Y., Leung, N.W.Y., Hussain, M., Wong, M.L. and Lok, A.S.F. (2000) Hepatitis B e Antigen-Negative Chronic Hepatitis B in Hong Kong. Hepatology, 31, 763-768. http://dx.doi.org/10.1002/hep.510310330
[11]	Zarski, J.P., Marcellin, P., Leroy, V., Trepo, C., Samuel, D., Ganne-Carrie, N., Barange, K., Canva, V., Doffoel, M. and Cales, P., Fédération nationale des Pôles de référence et des Réseaux Hépatites (2006) Characteristics of Patients with Chronic Hepatitis B in France: Predominant Frequency of HBe Antigen Negative Cases. Journal of Hepatology, 45, 355-360. http://dx.doi.org/10.1016/j.jhep.2006.03.007
[12]	Sagnelli, E., Stroffolini, T., Mele, A., Imparato, M. and Almasio, P.L., The Italian Hospitals’ Collaborating Group (2008) Chronic Hepatitis B in Italy: New Features of an Old Disease-Approaching the Universal Prevalence of Hepatitis B e Antigen—Negative Cases and the Eradication of Hepatitis D Infection. Clinical Infectious Diseases, 46, 110-113. http://dx.doi.org/10.1086/524074
[13]	Bedossa, P. and Poynard, T., The METAVIR Cooperative Study Group (1996) An Algorithm for the Grading of Activity in Chronic Hepatitis C. Hepatology, 24, 289-293. http://dx.doi.org/10.1002/hep.510240201
[14]	Zoulim, F. and Trepo, C. (2005) Histoire naturelle de l’hépatite B chronique. Journal de Pharmacie Clinique, 24, 233-237.
[15]	Dumpis, U., Holmes, E.C., Mendy, M., Hill, A., Thursz, M., Hall, A., Whittle, H. and Karayiannis, P. (2001) Transmission of Hepatitis B Virus Infection in Gambian Families Revealed by Phylogenetic Analysis. Journal of Hepatology, 35, 99-104. http://dx.doi.org/10.1016/S0168-8278(01)00064-2
[16]	Lee, W.M. (1997) Hepatitis B Virus Infection. New England Journal of Medicine, 337, 1733-1745. http://dx.doi.org/10.1056/NEJM199712113372406
[17]	Andoulo, F., Tagni-Sartre, M., Noah, D., Djapa, R. and Ndam, E. (2013) Prevalence of the Hepatitis B Surface Antigen in a Population of Workers in Cameroon. Open Journal of Gastroenterology, 3, 323-327. http://dx.doi.org/10.4236/ojgas.2013.38057
[18]	Ndumbe, P.M. and Njie, T.K. (1989) Hepatitis A and B Infections in Yaoundé, Cameroon. Research in Virology, 140, 253-261. http://dx.doi.org/10.1016/S0923-2516(89)80102-5
[19]	Mbanya, D.N., Takam, D. and Ndumbe, P.M. (2003) Serological Findings amongst First-Time Blood Donors in Yaoundé, Cameroon: Is Safe Donation a Reality or a Myth? Transfusion Medicine, 13, 267-273. http://dx.doi.org/10.1046/j.1365-3148.2003.00453.x
[20]	Pietra, V., Kiema, D., Sorgho, D., Kabore, S.P., Mande, S., Castelli, F., Puoti, M. and Simpore, J. (2008) Prévalence des marqueurs du virus de l’hépatite B et des anticorps contre le virus de l’hépatite C parmi le personnel du District Sanitaire de Nanoro, Burkina Faso. Science et Technique, Sciences de la Santé, 31, 53-59.
[21]	Allain, J.P., Candotti, D., Soldan, K., Sarkodie, F., Phelps, B., Giachetti, C., Shyamala, V., Yeboah, F., Anokwa, M., Owusu-Ofori, S. and Opare-Sem, O. (2003) The Risk of Hepatitis B Virus Infection by Transfusion in Kumasi, Ghana. Blood, 101, 2419-2425. http://dx.doi.org/10.1182/blood-2002-04-1084
[22]	Kra, O., N’Dri, N., Ehui, E., Ouattara, B. and Bissagnene, E. (2007) Prévalence de l’antigène HBs chez les donneurs de sang au centre régional de transfusion sanguine de Bouaké (Côte d’Ivoire) en 2001. Bulletin de la Société de Pathologie Exotique, 100, 127-129.
[23]	Sombié, R., Bougouma, A., Diallo, O., Bonkoungou, G., Cissé, R., Sangare, L., Sia, R., Serme, K. and Ilboudo, D. (2010) Hépatite B chronique: Aspects épidémiologique, diagnostique, thérapeutique et évolutif au centre hospitalier universitaire Yalgado Ouédraogo de Ouagadougou. Journal Africain d’Hépato-Gastroentérologie, 4, 3-10. http://dx.doi.org/10.1007/s12157-009-0137-2
[24]	Khelifa, F. and Thibault, V. (2009) Characteristics of Hepatitis B Viral Strains in Chronic Carrier Patients from North-East Algeria. Pathologie Biologie, 57, 107-113. http://dx.doi.org/10.1016/j.patbio.2008.07.031
[25]	Pioche, C., Brouard, C., Chevaliez, S., Alric, L., Couzigou, P., Delarocque-Astagneau, E., Denis, F., Goria, O., Guyader, D., Marcellin, P., Roudot-Thoraval, F., Roulot, D., Silvain, C., Zarski, J.P., Semaille, C. and Larsen, C. (2014) Hépatite B chronique: Prise en charge en France entre 2008 et 2011. Bulletin épidémiologique Hebdomadaire, 12, 210-216.
[26]	Ducancelle, A., Pivert, A. and Lunel-Fabiani, F. (2011) Les mutants précore et du promoteur basal du core du virus de l’hépatite B. Virologie, 15, 100-114.
[27]	Rey-Cuille, M.A., Njouom, R., Bekondi, C., Seck, A., Gody, C., Bata, P., Garin, B., Maylin, S., Chartier, L., Simon, F. and Vray, M. (2013) Hepatitis B Virus Exposure during Childhood in Cameroon, Central African Republic and Senegal after the Integration of HBV Vaccine in the Expanded Program on Immunization. Pediatric Infectious Disease Journal, 32, 1110-1115. http://dx.doi.org/10.1097/INF.0b013e31829be401
[28]	Botha, J.F., Ritchie, M.J., Dusheiko, G.M., Mouton, H.W. and Kew, M.C. (1984) Hepatitis B Virus Carrier State in Black Children in Ovamboland: Role of Perinatal and Horizontal Infection. The Lancet, 323, 1210-1212. http://dx.doi.org/10.1016/S0140-6736(84)91694-5
[29]	Lemoine, M., Nayagam, S. and Thursz, M. (2013) Viral Hepatitis in Resource-Limited Countries and Access to Antiviral Therapies: Current and Future Challenges. Future Virology, 8, 371-380. http://dx.doi.org/10.2217/fvl.13.11
[30]	Kfutwah, A.K., Tejiokem, M.C. and Njouom, R. (2012) A Low Proportion of HBeAg among HBsAg-Positive Pregnant Women with Known HIV Status Could Suggest Low Perinatal Transmission of HBV in Cameroon. Virology Journal, 9, 62. http://dx.doi.org/10.1186/1743-422X-9-62
[31]	Fomulu, N.J., Morfaw, F.L.I., Torimiro, J.N., Nana, P., Mve Koh, V. and Takang, W. (2013) Prevalence, Correlates and Pattern of Hepatitis B among Antenatal Clinic Attenders in Yaoundé-Cameroon: Is Perinatal Transmission of HBV Neglected in Cameroon? BMC Pregnancy and Childbirth, 13, 158. http://dx.doi.org/10.1186/1471-2393-13-158
[32]	Ducancelle, A., Abgueguen, P., Birguel, J., Mansour, W., Pivert, A., Le Guillou-Guillemette, H., Sobnangou, J.J., Rameau, A., Huraux, J.M. and Lunel-Fabian, F. (2013) High Endemicity and Low Molecular Diversity of Hepatitis B Virus Infections in Pregnant Women in a Rural District of North Cameroon. PLoS ONE, 8, e80346. http://dx.doi.org/10.1371/journal.pone.0080346
[33]	Liaw, Y.F. and Chu, C.M. (2009) Hepatitis B Virus Infection. The Lancet, 373, 582-592. http://dx.doi.org/10.1016/S0140-6736(09)60207-5
[34]	Chu, C.M. and Liaw, Y.F. (2007) Chronic Hepatitis B Virus Infection Acquired in Childhood: Special Emphasis on Prognostic and Therapeutic Implication of Delayed HBeAg Seroconversion. Journal of Viral Hepatitis, 14, 147-152. http://dx.doi.org/10.1111/j.1365-2893.2006.00810.x
[35]	Candotti, D., Danso, K. and Allain, J.P. (2007) Maternofetal Transmission of Hepatitis B Virus Genotype E in Ghana, West Africa. Journal of General Virology, 88, 2686-2695. http://dx.doi.org/10.1099/vir.0.83102-0
[36]	Livingston, S.E., Simonetti, J.P., Bulkow, L.R., Homan, C.E., Snowball, M.M., Cagle, H.H., Negus, S.E. and McMahon, B.J. (2007) Clearance of Hepatitis B e Antigen in Patients with Chronic Hepatitis B and Genotypes A, B, C, D, and F. Gastroenterology, 133, 1452-1457. http://dx.doi.org/10.1053/j.gastro.2007.08.010
[37]	Chu, C.J., Hussain, M. and Lok, A.S. (2002) Hepatitis B Virus Genotype B Is Associated with Earlier HBeAg Seroconversion Compared with Hepatitis B Virus Genotype C. Gastroenterology, 122, 1756-1762. http://dx.doi.org/10.1053/gast.2002.33588
[38]	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. and Mizokami, M. (2005) A New Subtype (Subgenotype) Ac (A3) of Hepatitis B Virus and Recombination between Genotypes A and E in Cameroon. Journal of General Virology, 86, 2047-2056. http://dx.doi.org/10.1099/vir.0.80922-0
[39]	Feld, J.J., Ayers, M., El-Ashry, D., Mazzulli, T., Tellier, R. and Heathcote, E.J. (2007) Hepatitis B Virus DNA Prediction Rules for Hepatitis B e Antigen-Negative Chronic Hepatitis B. Hepatology, 46, 1057-1070. http://dx.doi.org/10.1002/hep.21811
[40]	Seo, Y., Yoon, S., Nakaji, M., Yano, Y., Nagano, H., Ninomiya, T., Hayashi, Y. and Kasuga, M. (2003) Hepatitis B Virus DNA in Anti-HBe-Positive Asymptomatic Carriers. Intervirology, 46, 43-49. http://dx.doi.org/10.1159/000068123
[41]	Papatheodoridis, G.V., Manolakopoulos, S., Liaw, Y.F. and Lok, A. (2012) Follow-Up and Indications for Liver Biopsy in HBeAg-Negative Chronic Hepatitis B Virus Infection with Persistently Normal ALT: A Systematic Review. Journal of Hepatology, 57, 196-202. http://dx.doi.org/10.1016/j.jhep.2011.11.030
[42]	Iloeje, U.H., Yang, H.I., Su, J., Jen, C.L., You, S.L. and Chen, C.J., The Risk Evaluation of Viral Load Elevation and Associated Liver Disease/Cancer-In HBV (The REVEAL-HBV) Study Group (2006) Predicting Cirrhosis Risk Based on the Level of Circulating Hepatitis B Viral Load. Gastroenterology, 130, 678-686. http://dx.doi.org/10.1053/j.gastro.2005.11.016
[43]	Iloeje, U.H., Yang, H.I., Jen, C.L., Su, J., Wang, L.Y., You, S.L. and Chen, C.J., Risk Evaluation of Viral Load Elevation and Associated Liver Disease/Cancer-Hepatitis B Virus Study Group (2007) Risk and Predictors of Mortality Associated with Chronic Hepatitis B Infection. Clinical Gastroenterology and Hepatology, 5, 921-931. http://dx.doi.org/10.1016/j.cgh.2007.06.015
[44]	Fattovich, G., Bortolotti, F. and Donato, F. (2008) Natural History of Chronic Hepatitis B: Special Emphasis on Disease Progression and Prognostic Factors. Journal of Hepatology, 48, 335-352. http://dx.doi.org/10.1016/j.jhep.2007.11.011
[45]	Chu, C.M. and Liaw, Y.F. (2005) Genotype C Hepatitis B Virus Infection Is Associated with a Higher Risk of Reactivation of Hepatitis B and Progression to Cirrhosis than Genotype B: A Longitudinal Study of Hepatitis B e Antigen-Positive Patients with Normal Aminotransferase Levels at Baseline. Journal of Hepatology, 43, 411-417. http://dx.doi.org/10.1016/j.jhep.2005.03.018
[46]	Tai, D.I., Lin, S.M., Sheen, I.S., Chu, C.M., Lin, D.T. and Liaw, Y.F. (2009) Long-Term Outcome of Hepatitis B e Antigen-Negative Hepatitis B Surface Antigen Carriers in Relation to Changes of Alanine Aminotransferase Levels over Time. Hepatology, 49, 1859-1867. http://dx.doi.org/10.1002/hep.22878
[47]	Valente, F., do Lago, B.V., de Castro, C.A.V., de Almeida, A.J., Gomes, S.A. and Soares, C.C. (2010) Epidemiology and Molecular Characterization of Hepatitis B Virus in Luanda, Angola. Memórias do Instituto Oswaldo Cruz, 105, 970-977. http://dx.doi.org/10.1590/S0074-02762010000800004