Clinical Implications of Concurrent HBsAg/HBsAb Positivity (scape mutants) in patients with Chronic Hepatitis B infection

Iraj Shahramian, Seyed Mohsen Dehghani, Gholamhossein Fallahi, Ali Bazi, Omolbanin Sargazi-aval, Daryoush Rostami, Mojtaba Delaramnasab


AIM: Concurrent positivity for HBsAg and HBs antibody, a phenomenon closely related to HBsAg escape mutants, is an unusual serological pattern in hepatitis B virus (HBV) infection. There is limited information on the clinical course of patients with this serological pattern. Here, we aimed to describe and compare clinical features of patients with chronic HBV infection presented simultaneous HBsAg+/HBsAb+.

MATERIAL AND METHODS: This was a retrospective study on 309 patients with chronic HBV. The patients received either tenofovir, lamivudine, or no treatment based on the levels of liver enzymes. Serological profiles were recorded at and after six months of diagnosis. Statistical analysis was performed in SPSS 19.

RESULTS: From 309 chronically HBsAg positive patients, 10 (3.2%) showed concurrent positivity for HBsAg and HBsAb in their sera. There were no statistically significant associations between this pattern with either gender, age, and HBeAg status. However, there was a close association between HBsAg+/HBsAb+ status with seropositivity for anti-HBeAg (P=0.05). There were also no significant differences between AST and ALT levels (neither at the diagnosis and nor at the end of six months of diagnosis) between the distinct serological patterns.

CONCLUSION: It seems that patients with chronic HBV infection and persistent concurrent reactivity for HBsAg and HBsAb render comparable clinical course with those patients with single HBsAg positivity.


Schweitzer A, Horn J, Mikolajczyk RT, Krause G, Ott JJ. Estimations of worldwide prevalence of chronic hepatitis B virus infection: a systematic review of data published between 1965 and 2013, The Lancet 2015; 386 (10003): 1546-55.

Hossain MG, Ueda K. Investigation of a Novel Hepatitis B Virus Surface Antigen (HBsAg) Escape Mutant Affecting Immunogenicity, PLoS One 2017; 12 (1): e0167871. 10.1371/journal.pone.0167871

Bi X, Tong S. Impact of immune escape mutations and N-linked glycosylation on the secretion of hepatitis B virus virions and subviral particles: Role of the small envelope protein, Virology 2018; 518 358-68. 10.1016/j.virol.2018.03.011

Organization WH. Hepatitis B: Factsheet No. 204. 2015, Google Scholar 2015.

Bian T, Yan H, Shen L, Wang F, Cao Y, Zhang S, et al. Change of hepatitis B large surface antigen variants after 13 years universal vaccination program in China, J Virol 2013; JVI. 02127-13.

Servant-Delmas A, Ly TD, Hamon C, Houdah AK, Laperche S. Comparative Performance of Three Rapid HBsAg Assays for Detection of HBs Diagnostic Escape Mutants in Clinical Samples, J Clin Microbiol 2015; 53 (12): 3954-5. 10.1128/jcm.02117-15

Qin Y, Liao P. Hepatitis B virus vaccine breakthrough infection: surveillance of S gene mutants of HBV, Acta Virol 2018; 62 (2): 115-21. 10.4149/av_2018_210

Stirk H, Thornton J, Howard C. Atopological Model for Hepatitis B Surface Antigen, Intervirology 1992; 33 (3): 148-58.

Wang C-J, Sung S-Y, Chen D-S, Chen P-J. N-linked glycosylation of hepatitis B surface antigens is involved but not essential in the assembly of hepatitis delta virus, Virology 1996; 220 (1): 28-36.

Cooreman MP, Van Roosmalen MH, Te Morsche R, Sünnen CM, Schoondermark‐Van De Ven EM, Jansen JB, et al. Characterization of the reactivity pattern of murine monoclonal antibodies against wild‐type hepatitis B surface antigen to g145r and other naturally occurring “a” loop escape mutations, Hepatology 1999; 30 (5): 1287-92.

Zhang J-M, Xu Y, Wang X-Y, Yin Y-K, Wu X-H, Weng X-H, et al. Coexistence of hepatitis B surface antigen (HBsAg) and heterologous subtype-specific antibodies to HBsAg among patients with chronic hepatitis B virus infection, Clin Infect Dis 2007; 44 (9): 1161-9.

Yang Y, Nan Y, Cai J, Xu J, Huang Z, Cai X. The Thr to Met substitution of amino acid 118 in hepatitis B virus surface antigen escapes from immune-assay-based screening of blood donors, J Gen Virol 2016; 97 (5): 1210-7. 10.1099/jgv.0.000427

Xue Y, Wang MJ, Yang ZT, Yu DM, Han Y, Huang D, et al. Clinical features and viral quasispecies characteristics associated with infection by the hepatitis B virus G145R immune escape mutant, Emerg Microbes Infect 2017; 6 (3): e15. 10.1038/emi.2017.2

Liu W, Hu T, Wang X, Chen Y, Huang M, Yuan C, et al. Coexistence of hepatitis B surface antigen and anti-HBs in Chinese chronic hepatitis B virus patients relating to genotype C and mutations in the S and P gene reverse transcriptase region, Arch Virol 2012; 157 (4): 627-34.

Pancher M, Désiré N, Ngo Y, Akhavan S, Pallier C, Poynard T, et al. Coexistence of circulating HBsAg and anti-HBs antibodies in chronic hepatitis B carriers is not a simple analytical artifact and does not influence HBsAg quantification, J Clin Virol 2015; 62 32-7.

Seo SI, Choi HS, Choi BY, Kim HS, Kim HY, Jang MK. Coexistence of hepatitis B surface antigen and antibody to hepatitis B surface may increase the risk of hepatocellular carcinoma in chronic hepatitis B virus infection: a retrospective cohort study, J Med Virol 2014; 86 (1): 124-30.

Lee BS, Cho YK, Jeong SH, Lee JH, Lee D, Park NH, et al. Nationwide seroepidemiology of hepatitis B virus infection in South Korea in 2009 emphasizes the coexistence of HBsAg and anti‐HBs, J Med Virol 2013; 85 (8): 1327-33.

Lada O, Benhamou Y, Poynard T, Thibault V. Coexistence of hepatitis B surface antigen (HBs Ag) and anti-HBs antibodies in chronic hepatitis B virus carriers: influence of “a” determinant variants, J Virol 2006; 80 (6): 2968-75.

Harris BJ, Holzmayer V, Qureshi H, Khan MA, Khan SA, Salamat N, et al. Hepatitis B genotypes and surface antigen mutants present in Pakistani blood donors, PLoS One 2017; 12 (6): e0178988. 10.1371/journal.pone.0178988

Amini-Bavil-Olyaee S, Vucur M, Luedde T, Trautwein C, Tacke F. Differential impact of immune escape mutations G145R and P120T on the replication of lamivudine-resistant hepatitis B virus e antigen-positive and-negative strains, J Virol 2010; 84 (2): 1026-33.

Pu Z, Li D, Wang A, Su H, Shao Z, Zhang J, et al. Epidemiological characteristics of the carriers with coexistence of HB sAg and anti‐HB s based on a community cohort study, J Viral Hepat 2016; 23 (4): 286-93.

Colson P, Borentain P, Motte A, Henry M, Moal V, Botta-Fridlund D, et al. Clinical and virological significance of the co-existence of HBsAg and anti-HBs antibodies in hepatitis B chronic carriers, Virology 2007; 367 (1): 30-40.

Larralde O, Dow B, Jarvis L, Davidson F, Petrik J. Hepatitis B escape mutants in Scottish blood donors, Med Microbiol Immunol 2013; 202 (3): 207-14. 10.1007/s00430-012-0283-9

Lin CL, Kao JH. Natural history of acute and chronic hepatitis B: The role of HBV genotypes and mutants, Best Pract Res Clin Gastroenterol 2017; 31 (3): 249-55. 10.1016/j.bpg.2017.04.010

Hayashi J, Noguchi A, Nakashima K, Morofuji M, Kashiwagi S. Frequency of concurrence of hepatitis B surface antigen and antibody in a large number of carriers in Okinawa, Japan, Gastroenterol Jpn 1990; 25 (5): 593-7.

Full Text: PDF HTML


  • There are currently no refbacks.

Creative Commons License
This work is licensed under a Creative Commons Attribution 3.0 License.