Success of electrochemical immunosensors for the determination of hepatitis B surface antigen, an important clinical marker in the diagnosis of hepatitis B

Abstract

Infection with hepatitis B virus (HBV) is a global health problem, causing diseases such as acute and chronic hepatitis, liver cirrhosis, and hepatocellular carcinoma. Numerous studies in the literature have demonstrated hepatitis B surface antigen (HBsAg) as the first virological marker of HBV infection, and that serum HBsAg levels are reported to be an important criterion for the diagnosis and management of HBV infection. Therefore, the sensitive and selective detection of HBsAg is critical for the early diagnosis of hepatitis B and for the management of the diseases associated with HBV infection. Electrochemical immunosensors play an important role in the early diagnosis of infection with hepatitis B virus since they are rapid, easy-to-use, and reliable diagnostic tools with a possibility of on-site detection. Besides, they might have superior performance in terms of multiple analytical parameters compared to more commonly used alternatives in the clinic, including ELISA. Herein, we review the reported success and potential of electrochemical biosensors for the detection of HBsAg in the early diagnosis and monitoring of hepatitis B virus infection, and provide a brief overview for future studies, with the ultimate aim of directing more research focus into this topic.

Keywords

Hepatitis B virus / Hepatitis B surface antigen / Immunosensor / Infection diagnosis / Early diagnosis / Hepatitis B

References

[1] Berkel C, Özbek O, Altunoluk OC, Eski İM. A review on nanostructured electrochemical immunosensors for the determination of HER2, a breast cancer biomarker. Journal of NanoScience in Advanced Materials, 2025, 4(2): 58-66

[2] Berkel C, Özbek O, Altunoluk OC. Potential of potentiometric biosensors for the study of ion influx and efflux via gasdermin pores in plasma membrane in pyroptosis: A hypothesis. Human Cell, 2026, 39(1): 30

[3] Chang, M. H. (2007). Hepatitis B virus infection. In Seminars in fetal and neonatal medicine 12, 160–167.

[4] Chen Y, Wang J, Liu Z, Wu G. Determination of hepatitis B virus surface antigen in serum with a sandwich immunoassay and capillary electrophoresis–electrochemical detection. Analytical Methods, 2014, 6: 2484-2489

[5] Donato F, Boffetta P, Puoti M. A meta-analysis of epidemiological studies on the combined effect of hepatitis B and C virus infections in causing hepatocellular carcinoma. International Journal of Cancer, 1998, 75(3): 347-354

[6] Gnyawali B, Pusateri A, Nickerson A, Jalil S, Mumtaz K. Epidemiologic and socioeconomic factors impacting hepatitis B virus and related hepatocellular carcinoma. World Journal of Gastroenterology, 2022, 28(29): 3793

[7] Jeng WJ, Papatheodoridis GV, Lok ASF. Hepatitis B Lancet, 2023, 401103811039-1052

[8] Komatsu H, Inui A, Sogo T, Tateno A, Shimokawa R, Fujisawa T. Tears from children with chronic hepatitis B virus (HBV) infection are infectious vehicles of HBV transmission: Experimental transmission of HBV by tears, using mice with chimeric human livers. The Journal of Infectious Diseases, 2012, 206(4): 478-485

[9] Lee KI, Liang PC, Hsu PY, Jang TY, Wei YJ, Huang CI, Hsieh MY, Lin ZY, Yeh ML, Huang CF, Huang JF, Dai CY, Chuang WL, Yu ML. Unawareness of hepatitis B infection and lack of surveillance are associated with severity of hepatocellular carcinoma. The Kaohsiung Journal of Medical Sciences, 2023, 39(11): 1145-1154

[10] Li X, Liu T, Zhang Y, Ni X, Hossain MN, Chen X, Huang H, Kraatz HB. A novel electrochemical immunosensor for hepatitis B surface antigen based on Fe3O4 nanoflowers and heterogeneous chain reaction signal amplification strategy. Talanta, 2021, 221: 121459 Epub 2020 Jul 31. PMID: 33076081

[11] Li, M., Tao, C., Tang, Z., Li, K., Wang, Y., Zhao, C., Tao, C., Geng, J., & Sun, K. (2025). Ultrasensitive clinical identification of hepatitis B surface antigen (HBsAg) by CRISPR-assisted nanopore sensing. Biosensors and Bioelectronics, 286, 117579.

[12] Lim JK, Nguyen MH, Kim WR, Gish R, Perumalswami P, Jacobson IM. Prevalence of chronic hepatitis B virus infection in the united States. Official Journal of the American College of Gastroenterology| ACG, 2020, 115(9): 1429-1438

[13] Mahoney FJ. Update on diagnosis, management, and prevention of hepatitis B virus infection. Clinical Microbiology Reviews, 1999, 12(2): 351-366

[14] Nourani S, Ghourchain H, Boutorabi SM. Magnetic nanoparticle-based immunosensor for electrochemical detection of hepatitis B surface antigen. Analytical Biochemistry, 2013, 441: 1-7

[15] Özbek O, Eski IM, Berkel C. Success of electrochemical biosensors developed for the determination of amyloid-beta 42 (Aβ42) protein in the diagnosis of alzheimer’s disease. Genome Instability & Disease, 2025, 6(4): 347-350

[16] Pei F, Wang P, Ma E, Yang Q, Yu H, Gao C, Li Y, Liu Q, Dong Y. A sandwich-type electrochemical immunosensor based on RhPt NDs/NH2-GS and Au NPs/PPy NS for quantitative detection hepatitis B surface antigen. Bioelectrochemistry, 2019, 126: 92-98

[17] Petruzziello A. Epidemiology of hepatitis B virus (HBV) and hepatitis C virus (HCV) related hepatocellular carcinoma. The Open Virology Journal, 2018, 12: 26

[18] Sabeena S, Ravishankar N. Horizontal modes of transmission of hepatitis B virus (HBV): A systematic review and meta-analysis. Iranian Journal of Public Health, 2022, 51(10): 2181

[19] Seeger C, Mason WS. Hepatitis B virus biology. Microbiology and Molecular Biology Reviews, 2000, 64151-68

[20] Shi J, Zhu L, Liu S, Xie WF. A meta-analysis of case–control studies on the combined effect of hepatitis B and C virus infections in causing hepatocellular carcinoma in China. British Journal of Cancer, 2005, 92(3): 607-612

[21] Song Z, Lin S, Wu X, Ren X, Wu Y, Wen H, Shen S. Hepatitis B virus-related intrahepatic cholangiocarcinoma originates from hepatocytes. Hepatology International, 2023, 17(5): 1300-1317

[22] Tan Z, Dong H, Liu Q, Lui H, Zhap P, Wang P, Li Y, Zhang D, Zhao Z, Dong Y. A label-free immunosensor based on PtPd NCs@MoS2 nanoenzymes for hepatitis B surface antigen detection. Biosensors and Bioelectronics, 2019, 142: 111556

[23] Tang D, Yuan R, Chai Y, Zhong X, Liu Y, Dai J. Electrochemical detection of hepatitis B surface antigen using colloidal gold nanoparticles modified by a sol–gel network interface. Clinical Biochemistry, 2006, 39: 309-314

[24] Teengam P, Tangkijvanich P, Chuaypen N, Chailapakul O. An innovative wireless electrochemical card sensor for field-deployable diagnostics of hepatitis B surface antigen. Scientific Reports, 2023, 13(1): 3523

[25] Tyas AA, Sakti SP, Nacapricha D, Uraisin K, Susianti H, Sabarudin A, Saetear P. Reduced graphene oxide-gold/methylene blue composite on miniaturized electrochemical immunosensor for the label-free voltammetric determination of hepatitis B surface antigen. Microchemical Journal, 2025, 212: 113328

[26] Wei S, Xiao H, Cao L, Chen Z. A label-free immunosensor based on graphene oxide/Fe3O4/prussian blue nanocomposites for the electrochemical determination of HBsAg. Biosensors, 2020, 10324

[27] World Health Organization. Guidelines on Hepatitis B and C Testing. Geneva (WHO, 2017).

[28] Xi Z, Gong Q, Wang C, Zheng B. Highly sensitive chemiluminescent aptasensor for detecting HBV infection based on rapid magnetic separation and double-functionalized gold nanoparticles. Scientific Reports, 2018, 819444

[29] Yuen MF, Chen DS, Dusheiko GM, Janssen HL, Lau DT, Locarnini SA, Peters MG, Lai CL. Hepatitis B virus infection. Nature Reviews Disease Primers, 2018, 411-20

[30] Yuliarto, B., Septiani, N. L. W., Dewi, K. K., Raihan, M. F., & Wustoni, S. (2024). HBV-Testing: HKUST-1-modified electrochemical immunosensor for Point-of-Care testing of hepatitis B. IEEE Sensors Journal.

RIGHTS & PERMISSIONS

Shenzhen University School of Medicine; Fondazione Istituto FIRC di Oncologia Molecolare