Correlation between serum quantitative HBsAg and HBV DNA levels in chronic hepatitis B patients

Maria  Pete; Maja Ružić; Nadica Kovačević; Vedrana Petrić; Ivana Milošević; Tomislav Preveden

doi:10.2298/VSP220528086P

Maria Pete University Clinical Center of Vojvodina, Clinic for Infectious Diseases, Novi Sad, Serbia
Maja Ružić University Clinical Center of Vojvodina, Clinic for Infectious Diseases, Novi Sad, Serbia
Nadica Kovačević University Clinical Center of Vojvodina, Clinic for Infectious Diseases, Novi Sad, Serbia
Vedrana Petrić University Clinical Center of Vojvodina, Clinic for Infectious Diseases, Novi Sad, Serbia
Ivana Milošević University Clinical Center of Serbia, Clinic for Infectious and Tropical Diseases, Belgrade, Serbia
Tomislav Preveden University Clinical Center of Vojvodina, Clinic for Infectious Diseases, Novi Sad, Serbia

DOI: https://doi.org/10.2298/VSP220528086P

Keywords: biomarkers, drug therapy, hepatitis b, hepatitis b, e antigens, hepatitis b surface antigens, hepatitis b virus

Abstract

Background/Aim. Quantitative hepatitis B virus (HBV) surface antigen (qHBsAg) has become increasingly widespread in the last few years in both diagnostic and therapeutic protocols for HBV infection. Numerous studies have proposed it as a surrogate marker for covalently closed circular DNA (cccDNA). The aim of the study was to determine the correlation between qHBsAg and HBV DNA viremia in untreated patients. Methods. The study included 112 untreated patients diagnosed with chronic HBV infection. Demographic and other data from medical records and laboratory analyses, taken as part of routine chronic HBV infection diagnosis with the determination of qHBsAg and HBV DNA viremia, were recorded for all patients. Results. The average age of the patients included in the study was 48.27 ± 15.14 years; males (58%) were more represented. qHBsAg levels had a high-intensity positive correlation with HBV DNA viremia. The concentration of qHBsAg, HBV DNA viremia, and the concentrations of alanine aminotransferase and aspartate aminotransferase showed statistically significantly higher values in HBV e antigen (HBeAg)-positive than in HBeAg-negative patients. Conclusion. Our study showed that qHBsAg has a high-intensity positive correlation with HBV DNA viremia. The use of qHBsAg is essential for determining the phase of chronic HBV infection, assessment of the success and length of treatment, as well as for safe discontinuation of antiviral therapy with a lower risk of relapse.

Author Biography

Maria Pete, University Clinical Center of Vojvodina, Clinic for Infectious Diseases, Novi Sad, Serbia

Lekar opšte prakse

References

1. European Association for the Study of the Liver. European Association for the Study of the Liver. EASL 2017 Clinical Practice Guidelines on the management of hepatitis B virus infection. J Hepatol 2017; 67(2): 370‒98.

2. Božić M, editor. Therapeutic options for chronic hepatitis B and C and the possibility of eliminating the viruses. Belgrade: Academy of Medical Sciences of the Serbian Medical Society; 2020. (Serbian)

3. Lin S, Zhang YJ. Interference of Apoptosis by Hepatitis B Virus. Viruses 2017; 9(8): 230.

4. Lim JK, Nguyen MH, Kim WR, Gish R, Perumalswami P, Jacobson IM. Prevalence of Chronic Hepatitis B Virus Infection in the United States. Am J Gastroenterol 2020; 115(9): 1429‒38.

5. 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. Lancet 2015; 386(10003): 1546‒55.

6. Günal Ö, Barut Ş, Etikan İ, Duygu F, Tuncel U, Sünbül M. Relation between serum quantitative HBsAg, ALT and HBV DNA levels in HBeAg negative chronic HBV infection. Turk J Gastroenterol 2014; 25(1 Suppl): 142‒6.

7. Leroi C, Adam P, Khamduang W, Kawilapat S, Ngo-Giang-Huong N, Ongwandee S, et al. Prevalence of chronic hepatitis B virus infection in Thailand: a systematic review and meta-analysis. Int J Infect Dis 2016; 51: 36‒43.

8. Laras A, Papatheodoridi M, Panopoulou E, Papatheodoridis GV, Hadziyannis SJ, Hadziyannis E. Serum hepatitis B virus RNA detectability, composition and clinical significance in patients with ab initio hepatitis B e antigen negative chronic hepatitis B. Virol J 2022; 19(1): 22.

9. Moini M, Fung S. HBsAg Loss as a Treatment Endpoint for Chronic HBV Infection: HBV Cure. Viruses 2022; 14(4): 657.

10. Lee JM, Ahn SH. Quantification of HBsAg: basic virology for clinical practice. World J Gastroenterol 2011; 17(3): 283‒9.

11. Ungtrakul T, Sriprayoon T, Kusuman P, Chunnuan P, Soonklang K, Sornsamdang G, et al. Role of quantitative hepatitis B surface antigen in predicting inactive carriers and HBsAg seroclearance in HBeAg-negative chronic hepatitis B patients. Medicine (Baltimore) 2017; 96(13): E6554.

12. Baudi I, Inoue T, Tanaka Y. Novel Biomarkers of Hepatitis B and Hepatocellular Carcinoma: Clinical Significance of HBcrAg and M2BPGi. Int J Mol Sci 2020; 21(3): 949.

13. Yang N, Feng J, Zhou T, Li Z, Chen Z, Ming K, et al. Relationship between serum quantitative HBsAg and HBV DNA levels in chronic hepatitis B patients. J Med Virol 2018; 90(7): 1240‒5.

14. Larsson SB, Malmström S, Hannoun C, Norkrans G, Lindh M. Mechanisms downstream of reverse transcription reduce serum levels of HBV DNA but not of HBsAg in chronic hepatitis B virus infection. Virol J 2015; 12: 213.

15. von Bömmel F, Bartens A, Mysickova A, Hofmann J, Krüger DH, Berg T, et al. Serum hepatitis B virus RNA levels as an early predictor of hepatitis B envelope antigen seroconversion during treatment with polymerase inhibitors. Hepatolоgy 2015; 61(1): 66‒76.

16. Assis DR, Tenore Sde B, Pinho JR, Lewi DS, Ferreira PR. Characteristics of an outpatient chronic hepatitis B virus infection cohort. Einstein (Sao Paulo) 2015; 13(2): 189‒95.

17. Bixler D, Zhong Y, Ly KN, Moorman AC, Spradling PR, Teshale EH, et al. Mortality among patients with chronic hepatitis B infection: the Chronic Hepatitis Cohort Study (CHeCS). Clin Infect Dis 2019; 68(6): 956‒63.

18. Terrault NA, Lok ASF, McMahon BJ, Chang KM, Hwang JP, Jonas MM, et al. Update on prevention, diagnosis, and treatment of chronic hepatitis B: The American Association for the Study of Liver Diseases AASLD 2018 hepatitis B guidance. Hepatology 2018; 67(4): 1560‒99.

19. Cornberg M, Wong VW, Locarnini S, Brunetto M, Janssen HLA, Chan HL. The role of quantitative hepatitis B surface antigen revisited. J Hepatol 2017; 66(2): 398‒411.

20. Delić D. Chronic viral hepatitis. Belgrade: Public Institute for textbooks; 2018. (Serbian)

21. The World Health Organization. Hepatitis B. 2020 [cited 2020 Aug 23]. Available from: https://www.who.int/news-room/factsheets/detail/hepatitis-b.>

22. Ghany MG, Morgan TR. AASLD-IDSA Hepatitis C Guidance Panel. Hepatitis C Guidance 2019 Update: American Association for the Study of Liver Diseases-Infectious Diseases Society of America Recommendations for Testing, Managing, and Treating Hepatitis C Virus Infection. Hepatology 2020; 71(2): 686‒721.

23. Degushi M, Yamashita N, Kagita M, Asari S, Iwatani Y, Tsuchida T, et al. Quantitation of hepatitis B surface antigen by an automated chemiluminiscent microparticle immunoassay. J Virol Methods 2004; 115(2): 217‒22.

24. Chan HL, Wong VW, Wong GL, Tse CH, Chan HY, Sung JJ. A longitudinal study on the natural history of serum hepatitis B surface antigen changes in chronic hepatitis B. Hepatology 2010; 52(4): 1232‒41.

25. Zoulim F, Carosi G, Greenbloom S, Mazur W, Nguyen T, Jeffers L, et al. Quantification of HBsAg in nucleos(t)ide-naïve patients treated for chronic hepatitis B with entecavir with or without tenofovir in the BE-LOW study. J Hepatol 2015; 62(1): 56‒63.

26. Zhu HY, Zhang XS. Relationship between HBV DNA load and levels of serum HBsAg in patients with chronic hepatitis B. Eur Rev Med Pharmacol Sci 2016; 20(10): 2061‒4.

27. Jaroszewicz J, Calle Serrano B, Wursthorn K, Deterding K, Schlue J, Raupach R, et al. Hepatitis B surface antigen (HBsAg) levels in the natural history of hepatitis B virus (HBV)-infection: A European perspective. J Hepatol 2010; 52(4): 514‒22.

28. Ganji A, Esmaeilzadeh A, Ghafarzadegan K, Helalat H, Rafatpanah H, Mokhtarifar A. Correlation between HBsAg quantitative assay results and HBV DNA levels in chronic HBV. Hepat Mon 2011; 11(5): 342‒5.

29. Mahdavi MR, Haghshenas MR, Roshan P, Hojjati MT, Mahdavi M, Jalali H, et al. Is quantitative HBsAg measurement a reliable substitute for HBV DNA quantitation? Res Mol Med 2015; 3(3): 33‒7.

30. Pita I, Horta Vale AM, Cardoso H, Macedo G. Hepatitis B inactive carriers: an overlooked population? GE Port J Gastroenterol 2014; 21(6): 241‒9.

31. Togo S, Arai M, Tawada A, Chiba T, Kanda T, Fujiwara K, et al. Clinical importance of serum hepatitis B surface antigen levels in chronic hepatitis B. J Viral Hepat 2011; 18(10): e508‒15.