Hepatitis B Virus_Surface Gene Mutations and Their Clinical Implications
Hepatitis B infection is a major public health problem caused by hepatitis B virus (HBV). Factors associated with host immunity such as (HBV specific T- and/or B-cell) production and antigen presentation failure and viral determinants such as the HBV genotypes and their evolving variants, have largely contributed to and justified variations that occur in the HBV surface gene. Hepatitis B surface gene mutations may influence the accuracy of the results obtained with currently used serological diagnostic tests and may represent a great risk for the community, since neither hepatitis B vaccines nor hepatitis B immunoglobulin will prevent the infection by HBV. Out of 96 published papers from (1988 till 2016) downloaded from Google scholar and PubMed and evaluated according to the relevance of scientific data for the surface gene mutations of hepatitis B virus then52 papers of them were selected and included in this study, then we reviewed and evaluated the current published papers about the surface gene mutations worldwide in which G145R represents the most common hepatitis B surface gene mutation reported in the literature. Furthermore, we reviewed their clinical implications and their impact on hepatitis B vaccination and treatment.
 H. B. El-Serag, “Hepatocellular carcinoma,” The New England Journal of Medicine, vol. 365, no. 12, pp. 1118–1127, 2011.
 C. Gilbert and C. Feschotte, “Genomic fossils calibrate the long-term evolution of hepadnaviruses,” PLoS Biology, vol. 8, no. 9, Article ID e1000495, 2010.
 WHO, World Health Organization Fact Sheet, 2015. N°204.
 K. V. Kowdley, C. C. Wang, S. Welch, H. Roberts, and C. L. Brosgart, “Prevalence of chronic hepatitis B among foreign-born persons living in the United States by country of origin,” Hepatology, vol. 56, no. 2, pp. 422–433, 2012.
 H. M. Mudawi, “Epidemiology of viral hepatitis in Sudan,” Clinical and Experimental Gastroenterology, vol. 1, pp. 9–13, 2008.
 A. O. Santos, M. V. Alvarado-Mora, L. Botelho et al., “Characterization of Hepatitis B virus (HBV) genotypes in patients from Rondônia, Brazil,” Virology Journal, vol. 7, article no. 315, 2010.
 T. J. Liang, “Hepatitis B: the virus and disease,” Hepatology, vol. 49, 5, pp. S13–S21,2009.
 T. Pollicino, I. Cacciola, F. Saffioti, and G. Raimondo, “Hepatitis B virus PreS/S gene variants: pathobiology and clinical implications,” Journal of Hepatology, vol. 61, no. 2, pp. 408–417, 2014.
 A. Bertoletti and A. J. Gehring, “The immune response during hepatitis B virus infection,” Journal of General Virology, vol. 87, no. 6, pp. 1439–1449, 2006.
 J. M. Murray, S. F. Wieland, R. H. Purcell, and F. V. Chisari, “Dynamics of hepatitis B virus clearance in chimpanzees,” Proceedings of the National Academy of Sciences of the United States of America, vol. 102, no. 49, pp. 17780–17785, 2005.
 J. J. Chang and S. R. Lewin, “Immunopathogenesis of hepatitis B virus infection,” Immunology and Cell Biology, vol. 85, no. 1, pp. 16–23, 2007.
 R. J. Lamontagne, S. Bagga, and M. J. Bouchard, “Hepatitis B virus molecular biology and pathogenesis,” Hepatoma Research, vol. 2, no. 7, pp. 163–168, 2016.
 X. Qiu, L. Song, S. Yang et al., “A fast and low-cost genotyping method for hepatitis B virus based on pattern recognition in point-of-care settings,” Scientific Reports, vol. 6, Article ID 28274, 2016.
 C.-T. Wai, R. J. Fontana, J. Polson et al., “Clinical outcome and virological characteristics of hepatitis B-related acute liver failure in the United States,” Journal of Viral Hepatitis, vol. 12, no. 2, pp. 192–198, 2005.
 V. Thakur, R. C. Guptan, S. N. Kazim, V. Malhotra, and S. K. Sarin, “Profile, spectrum and significance of HBV genotypes in chronic liver disease patients in the Indian Subcontinent,” Journal of Gastroenterology and Hepatology, vol. 17, no. 2, pp. 165– 170, 2002.
 M.-W. Yu, S.-H. Yeh, P.-J. Chen et al., “Hepatitis B virus genotype and DNA level and hepatocellular carcinoma: A prospective study in men,” Journal of the National Cancer Institute, vol. 97, no. 4, pp. 265–272, 2005.
 T. Inoue and Y. Tanaka, “Hepatitis B virus and its sexually transmitted infection ? an update,” Microbial Cell, vol. 3, no. 9, pp. 419–436, 2016.
 J. E. Newbold, H. Xin, M. Tencza et al., “The covalently closed duplex form of the hepadnavirus genome exists in situ as a heterogeneous population of viral minichromosomes,” Journal of Virology, vol. 69, no. 6, pp. 3350–3357, 1995.
 S. Locarnini, “Molecular virology and the development of resistant mutants: Implications for therapy,” Seminars in Liver Disease, vol. 25, no. 1, pp. 9–19, 2005.
 D. Grimm, R. Thimme, and H. E. Blum, “HBV life cycle and novel drug targets,” Hepatology International, vol. 5, no. 2, pp. 644–653, 2011.
 H. Norder, A.-M. Couroucé, P. Coursaget et al., “Genetic diversity of hepatitis B virus strains derived worldwide: Genotypes, subgenotypes, and HBsAg subtypes,” Intervirology, vol. 47, no. 6, pp. 289–309, 2004.
 T. Guettouche and H. J. Hnatyszy, “Chronic hepatitis B and viral genotypes,” in Antivir Ther, pp. 593–604, 10/5, 593-604, 2005.
 D. J. Tenney, R. E. Rose, C. J. Baldick et al., “Long-term monitoring shows hepatitis B virus resistance to entecavir in nucleoside-naïve patients is rare through 5 years-of therapy,” Hepatology, vol. 49, no. 5, pp. 1503–1514, 2009.
 C.-L. Lai, E. Gane, Y.-F. Liaw et al., “Telbivudine versus lamivudine in patients with chronic hepatitis B,” New England Journal of Medicine, vol. 357, no. 25, pp. 2576– 2588, 2007.
 C. W. Shepard, E. P. Simard, L. Finelli, A. E. Fiore, and B. P. Bell, “Hepatitis B virus infection: epidemiology and vaccination,” Epidemiologic Reviews, vol. 28, no. 1, pp. 112–125, 2006.
 B. J. McMahon, “The natural history of chronic hepatitis B virus infection,” Hepatology, vol. 49, no. 5, pp. S45–S55, 2009.
 B. A. Antoni, I. Rodríguez-Crespo, J. Gómez-Gutiérrez, M. Nieto, D. Peterson, and F. Gavilanes, “Site-directed mutagenesis of cysteine residues of hepatitis B surface antigen Analysis of two single mutants and the double mutant,” European Journal of Biochemistry, vol. 222, no. 1, pp. 121–127, 1994.
 P. Dindoost, S. M. Jazayeri, H. Karimzadeh, E. Saberfar, S. M. Miri, and S. M. Alavian, “HBsAg variants: Common escape issues,” Jundishapur Journal of Microbiology, vol. 5, no. 4, pp. 521–527, 2012.
 B. Weber, “Genetic variability of the S gene of hepatitis B virus: Clinical and diagnostic impact,” Journal of Clinical Virology, vol. 32, no. 2, pp. 102–112, 2005.
 M. L. Cuestas, V. L. Mathet, V. Ruiz et al., “Unusual naturally occurring humoral and cellular mutated epitopes of hepatitis B virus in a chronically infected Argentine patient with anti-HBs antibodies,” Journal of Clinical Microbiology, vol. 44, no. 6, pp. 2191–2198, 2006.
 M. A. Purdy, “Hepatitis B virus S genes escape mutants,” Asian J Transfus Sci, pp. 62–70, 2007.
 J. Samal, M. Kandpal, and P. Vivekanandan, “Molecular mechanisms underlying occult hepatitis B virus infection,” Clinical Microbiology Reviews, vol. 25, no. 1, pp. 142–163, 2012.
 Y. Tan, K. Ding, J. Su et al., “The naturally occurring YMDD mutation among patients chronically infected HBV and untreated with lamivudine: a systematic review and meta-analysis,” PLoS ONE, vol. 7, no. 3, Article ID e32789, 2012.
 G. M. Keating, S. Noble, F. M. Averhoff et al., “Recombinant hepatitis B vaccine (Engerix-B): A review of its immunogenicity and protective efficacy against hepatitis B,” Drugs, vol. 63, no. 10, pp. 1021–1051, 2003.
 P. F. Coleman, “Detecting hepatitis B surface antigen mutants,” Emerging Infectious Diseases, vol. 12, no. 2, pp. 198–203, 2006.
 A. R. Zanetti, E. Tanzi, G. Manzillo et al., “Hepatitis B variant in Europe,” Lancet, vol. 2, no. 8620, pp. 1132–1133, 1988.
 L. Sticchi, P. Caligiuri, R. Cacciani, C. Alicino, and B. Bruzzone, “Epidemiology of HBV S-gene mutants in the Liguria Region, Italy Implications for surveillance and detection of new escape variants,” Human Vaccines and Immunotherapeutics, vol. 9, no. 3, pp. 568–571, 2013.
 S. L. Ngui, S. O’Connell, R. P. Eglin, J. Heptonstall, and C. G. Teo, “Low detection rate and maternal provenance of hepatitis B virus S gene mutants in cases of failed postnatal immunoprophylaxis in England and Wales,” Journal of Infectious Diseases, vol. 176, no. 5, pp. 1360–1365, 1997.
 S. Datta, S. Chatterjee, V. Veer, and R. Chakravarty, “Molecular Biology of the Hepatitis B Virus for Clinicians,” Journal of Clinical and Experimental Hepatology, vol. 2, no. 4, pp. 353–365, 2012.
 C. He, F. Nomura, S. Itoga, K. Isobe, and T. Nakai, “Prevalence of vaccine-induced escape mutants of hepatitis B virus in the adult population in China: A prospective study in 176 restaurant employees,” Journal of Gastroenterology and Hepatology (Australia), vol. 16, no. 12, pp. 1373–1377, 2001.
 B. Moerman, V. Moons, H. Sommer, Y. Schmitt, and M. Stetter, “Evaluation of sensitivity for wild type and mutant forms of hepatitis B surface antigen by four commercial HBsAg assays,” Clinical Laboratory, vol. 50, no. 3-4, pp. 159–162, 2004.
 M. Luongo, R. Critelli, A. Grottola et al., “Acute hepatitis B caused by a vaccineescape HBV strain in vaccinated subject: Sequence analysis and therapeutic strategy,” Journal of Clinical Virology, vol. 62, pp. 89–91, 2015.
 C.-J. Oon, G.-K. Lim, Z. Ye et al., “Molecular epidemiology of hepatitis B virus vaccine variants in Singapore,” Vaccine, vol. 13, no. 8, pp. 699–702, 1995.
 A. D. Min and J. L. Dienstag, “Oral Antivirals for Chronic Hepatitis B,” Clinics in Liver Disease, vol. 11, no. 4, pp. 851–868, 2007.
 C. Trépo, H. L. Y. Chan, and A. Lok, “Hepatitis B virus infection,” The Lancet, vol. 384, no. 9959, pp. 2053–2063, 2014.
 S. Locarnini, A. Hatzakis, J. Heathcote et al., “Management of antiviral resistance in patients with chronic hepatitis B,” Antiviral Therapy, vol. 9, no. 5, pp. 679–693, 2004.
 A. Suk-Fong Lok, M. Hussain, C. Cursano et al., “Evolution of hepatitis B virus polymerase gene mutations in hepatitis B e antigen-negative patients receiving lamivudine therapy,” Hepatology, vol. 32, no. 5, pp. 1145–1153, 2000.
 S. N. Kazim, S. K. Sarin, B. C. Sharma, L. A. Khan, and S. E. Hasnain, “Characterization of naturally occurring and lamivudine-induced surface gene mutants of hepatitis B virus in patients with chronic hepatitis B in India,” Intervirology, vol. 49, no. 3, pp. 152–160, 2006.
 H.-Y. Lu, Z. Zeng, X.-Y. Xu, N.-L. Zhang, M. Yu, and W.-B. Gong, “Mutations in surface and polymerase gene of chronic hepatitis B patients with coexisting HBsAg and anti-HBs,” World Journal of Gastroenterology, vol. 12, no. 26, pp. 4219–4223, 2006.
 S. G. Selabe, E. Song, R. J. Burnett, and M. J. Mphahlele, “Frequent detection of hepatitis B virus variants associated with lamivudine resistance in treated South African patients infected chronically with different HBV genotypes,” Journal of Medical Virology, vol. 81, no. 6, pp. 996–1001, 2009.
 Y.-F. Liaw, R.-N. Chien, and C.-T. Yeh, “No benefit to continue lamivudine therapy after emergence of YMDD mutations,” Antiviral Therapy, vol. 9, no. 2, pp. 257–262, 2004.
 J.-H. Kao, “Molecular epidemiology of hepatitis B virus,” Korean Journal of Internal Medicine, vol. 26, no. 3, pp. 255–261, 2011.