Relationships between HBeAg status of patients with chronic hepatitis B and changes in serum TNF-α, viral load and severity of morphological changes in the liver according to non-invasive tests

Authors

DOI:

https://doi.org/10.14739/2310-1237.2021.1.228933

Keywords:

chronic hepatitis B, HBeAg, cytokines, liver fibrosis

Abstract

Aim – to investigate the relationship between HBeAg status of patients with chronic hepatitis B and the content of TNF-α in the serum, the level of viral load and the severity of morphological changes in the liver according to non-invasive tests.

Material and methods. 70 patients with CHB were examined. Noninvasive methods were used to determine the severity of morphological changes in the liver. The content of HBV-DNA in the blood was determined by PCR, HBeAg, anti-HBe, TNF-α by ELISA. Statistical processing was performed in Statistica 13 for Windows (StatSoft Inc., No. JPZ804I382130ARCN10-J).

Results. HBeAg-negative patients (78.6 %) with anti-HBe (89.1 %) predominate among patients with CHB. Lower frequency of seroconversion in patients with stages F 2–4, compared with patients with stages F 0-1 (85.7 % vs. 100 %, P < 0.05).

The highest level of HBV-DNA in the blood was in HBeAg-positive patients, compared with HBeAg-negative with stages F 0–1 (P < 0.05), of whom 83.3 % of patients had HBV-DNA >20000 IU/ml (83.3 % vs. 17.7 %). Viral load in HBeAg-positive patients with activity A 0–1 was the highest (P < 0.05), namely 4 times more often HBV-DNA was >20000 IU/ml, compared with HBeAg-negative (P < 0.05) A 0–1.

The content of TNF-α in the serum of patients with CHB was higher than in healthy individuals (P < 0.05). The highest content of TNF-α in the blood in HBeAg-positive patients with F 2–4, compared with HBeAg-negative with F 2–4 (P < 0.05). The severity of liver fibrosis correlated with the level of TNF-α (r = 0.31, P < 0.05).

Conclusions. HBeAg-negative (78.6 %) predominate among patients with CHB. In the presence of HBeAg-positive patients F 0–1 viral load is highest (P < 0.05). HBeAg-negative patients are 2.7 times more likely (P < 0.05) to have a viral load of HBV-DNA >20000 IU/ml in the presence of A 2–3 than in A 0–1. The highest content of TNF-α is in the serum of HBeAg-positive patients with F 2–4, compared with HBeAg-negative patients and the corresponding liver fibrosis (P < 0.05).

Author Biographies

A. B. Khelemendyk, Zaporizhzhia State Medical University, Ukraine

Assistant of the Department of Infectious Diseases

O. V. Riabokon, Zaporizhzhia State Medical University, Ukraine

MD, PhD, DSc, Professor, Head of the Department of Infectious Diseases

Yu. Yu. Riabokon, Zaporizhzhia State Medical University, Ukraine

MD, PhD, DSc, Professor of the Department of Children Infectious Diseases

K. V. Kalashnyk, Zaporizhzhia State Medical University, Ukraine

Assistant of the Department of Infectious Diseases

References

  1. Polaris Observatory Collaborators (2018). Global prevalence, treatment, and prevention of hepatitis B virus infection in 2016: a modelling study. The lancet. Gastroenterology & hepatology, 3(6), 383-403. https://doi.org/10.1016/S2468-1253(18)30056-6
  2. Zhang, Y., Zhang, H., Elizabeth, A., & Liu, X. Q. (2013). Epidemiology of hepatitis B and associated liver diseases in china. Chinese medical sciences journal, 27(4), 243-248. https://doi.org/10.1016/s1001-9294(13)60009-7
  3. World Health Organization. (2020, July 27). Hepatitis B. https://www.who.int/news-room/fact-sheets/detail/hepatitis-b
  4. Riabokon, O., Khelemendyk, A., & Riabokon, Y. (2018). Monitoring of patients with chronic hepatitis B without liver cirrhosis while determining the tactics of treatment. Pathologia, 15(2). https://doi.org/10.14739/2310-1237.2018.2.141428
  5. World Health Organization. (2015). Guidelines for the prevention care and treatment of persons with chronic hepatitis B infection. http://www.who.int/hiv/pub/hepatitis/hepatitis-b-guidelines/en/
  6. Arzumanyan, A., Reis, H., & Feitelson, M. (2013). Pathogenic mechanisms in HBV- and CHB-associated hepatocellular carcinoma. Nature Reviews Cancer, 13(2), 123-135. https://doi.org/10.1038/nrc3449
  7. Mitra, B., Thapa, R., Guo, H., & Block, T. (2018). Host functions used by hepatitis B virus to complete its life cycle: Implications for developing host-targeting agents to treat chronic hepatitis B. Antiviral Research, 158, 185-198. https://doi.org/10.1016/j.antiviral.2018.08.014
  8. Lang, T., Lo, C., Skinner, N., Locarnini, S., Visvanathan, K., & Mansell, A. (2011). The Hepatitis B e antigen (HBeAg) targets and suppresses activation of the Toll-like receptor signaling pathway. Journal of Hepatology, 55(4), 762-769. https://doi.org/10.1016/j.jhep.2010.12.042
  9. Terrault, N. A., Lok, A., McMahon, B. J., Chang, K. M., Hwang, J. P., Jonas, M. M., Brown, R. S., Jr, Bzowej, N. H., & Wong, J. B. (2018). Update on prevention, diagnosis, and treatment of chronic hepatitis B: AASLD 2018 hepatitis B guidance. Hepatology, 67(4), 1560-1599. https://doi.org/10.1002/hep.29800
  10. Larrubia, J. R., Benito-Martínez, S., Miquel-Plaza, J., Sanz-de-Villalobos, E., González-Mateos, F., & Parra, T. (2009). Cytokines - their pathogenic and therapeutic role in chronic viral hepatitis. Revista espanola de enfermedades digestivas, 101(5), 343-351. https://doi.org/10.4321/s1130-01082009000500006
  11. Chi, H., Hansen, B. E., Tang, W. Y., Schouten, J. N., Sprengers, D., Taimr, P., Janssen, H. L., & de Knegt, R. J. (2017). Multiple biopsy passes and the risk of complications of percutaneous liver biopsy. European journal of gastroenterology & hepatology, 29(1), 36-41. https://doi.org/10.1097/MEG.0000000000000731
  12. European Association for Study of Liver, & Asociacion Latinoamericana para el Estudio del Higado (2015). EASL-ALEH Clinical Practice Guidelines: Non-invasive tests for evaluation of liver disease severity and prognosis. Journal of hepatology, 63(1), 237-264. https://doi.org/10.1016/j.jhep.2015.04.006
  13. European Association for the Study of the Liver. (2017). EASL 2017 Clinical Practice Guidelines on the management of hepatitis B virus infection. Journal of hepatology, 67(2), 370-398. https://doi.org/10.1016/j.jhep.2017.03.021
  14. Mikolasevic, I., Orlic, L., Franjic, N., Hauser, G., Stimac, D., & Milic, S. (2016). Transient elastography (FibroScan(®)) with controlled attenuation parameter in the assessment of liver steatosis and fibrosis in patients with nonalcoholic fatty liver disease - Where do we stand?. World journal of gastroenterology, 22(32), 7236-7251. https://doi.org/10.3748/wjg.v22.i32.7236
  15. Parikh, P., Ryan, J. D., & Tsochatzis, E. A. (2017). Fibrosis assessment in patients with chronic hepatitis B virus (HBV) infection. Annals of translational medicine, 5(3), 40. https://doi.org/10.21037/atm.2017.01.28
  16. Jieanu, C. F., Ungureanu, B. S., Săndulescu, D. L., Gheonea, I. A., Tudorașcu, D. R., Ciurea, M. E., & Purcărea, V. L. (2015). Quantification of liver fibrosis in chronic hepatitis B virus infection. Journal of medicine and life, 8(3), 285-290.
  17. Zou, Z. Q., Wang, L., Wang, K., & Yu, J. G. (2016). Innate immune targets of hepatitis B virus infection. World journal of hepatology, 8(17), 716-725. https://doi.org/10.4254/wjh.v8.i17.716
  18. Busca, A., & Kumar, A. (2014). Innate immune responses in hepatitis B virus (HBV) infection. Virology journal, 11, 22. https://doi.org/10.1186/1743-422X-11-22
  19. Colombatto, P., Barbera, C., Bortolotti, F., Maina, A. M., Moriconi, F., Cavallone, D., Calvo, P., Oliveri, F., Bonino, F., & Brunetto, M. R. (2018). HBV pre-core mutant in genotype-D infected children is selected during HBeAg/anti-HBe seroconversion and leads to HBeAg negative chronic hepatitis B in adulthood. Journal of medical virology, 90(7), 1232-1239. https://doi.org/10.1002/jmv.25068
  20. Alexopoulou, A., & Karayiannis, P. (2014). HBeAg negative variants and their role in the natural history of chronic hepatitis B virus infection. World journal of gastroenterology, 20(24), 7644-7652. https://doi.org/10.3748/wjg.v20.i24.7644
  21. Wang, W. T., Zhao, X. Q., Li, G. P., Chen, Y. Z., Wang, L., Han, M. F., Li, W. N., Chen, T., Chen, G., Xu, D., Ning, Q., & Zhao, X. P. (2019). Immune response pattern varies with the natural history of chronic hepatitis B. World journal of gastroenterology, 25(16), 1950-1963. https://doi.org/10.3748/wjg.v25.i16.1950
  22. Baiocchini, A., Montaldo, C., Conigliaro, A., Grimaldi, A., Correani, V., Mura, F., Ciccosanti, F., Rotiroti, N., Brenna, A., Montalbano, M., D'Offizi, G., Capobianchi, M. R., Alessandro, R., Piacentini, M., Schininà, M. E., Maras, B., Del Nonno, F., Tripodi, M., & Mancone, C. (2016). Extracellular Matrix Molecular Remodeling in Human Liver Fibrosis Evolution. PloS one, 11(3), e0151736. https://doi.org/10.1371/journal.pone.0151736
  23. Suhail, M., Abdel-Hafiz, H., Ali, A., Fatima, K., Damanhouri, G. A., Azhar, E., Chaudhary, A. G., & Qadri, I. (2014). Potential mechanisms of hepatitis B virus induced liver injury. World journal of gastroenterology, 20(35), 12462-12472. https://doi.org/10.3748/wjg.v20.i35.12462
  24. Yao, Q. Y., Feng, Y. D., Han, P., Yang, F., & Song, G. Q. (2020). Hepatic microenvironment underlies fibrosis in chronic hepatitis B patients. World journal of gastroenterology, 26(27), 3917-3928. https://doi.org/10.3748/wjg.v26.i27.3917
  25. Deng, Y. Q., Zhao, H., Ma, A. L., Zhou, J. Y., Xie, S. B., Zhang, X. Q., Zhang, D. Z., Xie, Q., Zhang, G., Shang, J., Cheng, J., Zhao, W. F., Zou, Z. Q., Zhang, M. X., Wang, G. Q., & China HepB Related Fibrosis Assessment Research Group (2015). Selected Cytokines Serve as Potential Biomarkers for Predicting Liver Inflammation and Fibrosis in Chronic Hepatitis B Patients With Normal to Mildly Elevated Aminotransferases. Medicine, 94(45), e2003. https://doi.org/10.1097/MD.0000000000002003
  26. Lee, U. E., & Friedman, S. L. (2011). Mechanisms of hepatic fibrogenesis. Best practice & research. Clinical gastroenterology, 25(2), 195-206. https://doi.org/10.1016/j.bpg.2011.02.005
  27. Liu, C., Chen, X., Yang, L., Kisseleva, T., Brenner, D. A., & Seki, E. (2014). Transcriptional repression of the transforming growth factor β (TGF-β) Pseudoreceptor BMP and activin membrane-bound inhibitor (BAMBI) by Nuclear Factor κB (NF-κB) p50 enhances TGF-β signaling in hepatic stellate cells. The Journal of biological chemistry, 289(10), 7082–7091. https://doi.org/10.1074/jbc.M113.543769
  28. Tarrats, N., Moles, A., Morales, A., García-Ruiz, C., Fernández-Checa, J. C., & Marí, M. (2011). Critical role of tumor necrosis factor receptor 1, but not 2, in hepatic stellate cell proliferation, extracellular matrix remodeling, and liver fibrogenesis. Hepatology, 54(1), 319-327. https://doi.org/10.1002/hep.24388

Downloads

Published

2021-05-18

How to Cite

1.
Khelemendyk AB, Riabokon OV, Riabokon YY, Kalashnyk KV. Relationships between HBeAg status of patients with chronic hepatitis B and changes in serum TNF-α, viral load and severity of morphological changes in the liver according to non-invasive tests. Pathologia [Internet]. 2021May18 [cited 2026Jun.5];18(1):80-5. Available from: https://pat.zsmu.edu.ua/article/view/228933

Issue

Vol. 18 No. 1 (2021)

Section

Original research

License

Authors retain copyright and grant the journal right of first publication with the work simultaneously licensed under a Creative Commons Attribution License that allows others to share the work with an acknowledgement of the work's authorship and initial publication in this journal.

Лицензия Creative Commons