Skip to main content

Advertisement

SpringerLink
Log in

Circulating Biomarkers and their Possible Role in Pathogenesis of Chronic Hepatitis B and C Viral Infections

  • Original Article
  • Published:
Indian Journal of Clinical Biochemistry Aims and scope Submit manuscript

Abstract

The present study evaluated the plausible role of circulating biomarkers in immune pathogenesis of chronic hepatitis considered a priority in clinical hepatology. Total viral load of chronic hepatitis B virus (HBV) and hepatitis C virus (HCV) patients was quantified and correlation studies were performed with circulating levels of Th1/Th2 cytokines; C reactive protein and circulating nucleosomes; glutathione reductase (GR) and superoxide dismutase. To our knowledge, the study is first among its kind that validates strong positive correlation of viral load with IL-4, IL-6, GR in HBV and IL-6, IL-10, GR in HCV infections. Although, multi-centric studies including large cohorts are required for translating our findings to clinical practice, however, role of these biomarkers with potential diagnostic or prognostic significance might be helpful in clinical assessment of high-risk individuals, thereby, designing interventional strategies, towards development of personalized medicare. The results of our study also offer valuable insights of immune signaling mediators engaged in development of hepatocellular carcinoma.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. Hepatitis B. Vaccines. Wkly Epidemiol Rec. 2004;9:255–63.

    Google Scholar 

  2. Shepard CW, Simard EP, Finelli L, Fiore AE, Bell BP. Hepatitis B virus infection: epidemiology and vaccination. Epidemiol Rev. 2006;28:112–25.

    Article  PubMed  Google Scholar 

  3. Alter MJ. Epidemiology of hepatitis C virus infection. World J Gastroenterol. 2007;13:2436–41.

    PubMed  Google Scholar 

  4. Modlin RL, Nutman TB. Type 2 cytokines and negative immune regulation in human infections. Curr Opin Immunol. 1993;5:511–4.

    Article  PubMed  CAS  Google Scholar 

  5. NIH Consensus Statement on Management of Hepatitis C. NIH Consens State Sci Statements. 2002;19:1–46.

    Google Scholar 

  6. Hultgren C, Milich DR, Weiland O, Sallberg M. The antiviral compound ribavirin modulates the T helper (Th) 1/Th2 subset balance in hepatitis B and C virus-specific immune responses. J Gen Virol. 1998;10:2381–91.

    Google Scholar 

  7. Fan XG, Liu WE, Li CZ, Wang ZC, Luo LX, Tan DM, et al. Circulating Th1 and Th2 cytokines in patients with hepatitis C virus infection. Mediators Inflamm. 1998;7:295–7.

    Article  PubMed  CAS  Google Scholar 

  8. Ramadori G, Armbrust T. Cytokines in the liver. Eur J Gastroenterol Hepatol. 2001;13:777–84.

    Article  PubMed  CAS  Google Scholar 

  9. Moriya K, Nakagawa K, Santa T, Shintani Y, Fujie H, Miyoshi H, et al. Oxidative stress in the absence of inflammation in a mouse model for hepatitis C virus-associated hepatocarcinogenesis. Cancer Res. 2001;61:4365–70.

    PubMed  CAS  Google Scholar 

  10. Hoek JB, Pastorino JG. Ethanol, oxidative stress, and cytokine-induced liver cell injury. Alcohol. 2002;27:63–8.

    Article  PubMed  CAS  Google Scholar 

  11. Farinati F, Cardin R, Degan P, De Maria N, Floyd RA, Van Thiel DH, et al. Oxidative DNA damage in circulating leukocytes occurs as an early event in chronic HCV infection. Free Radic Biol Med. 1999;27:1284–91.

    Article  PubMed  CAS  Google Scholar 

  12. Chen CJ, Yang HI, Su J, Jen CL, You SL, Lu SN, et al. Risk of hepatocellular carcinoma across a biological gradient of serum hepatitis B virus DNA level. JAMA. 2006;295:65–73.

    Article  PubMed  CAS  Google Scholar 

  13. Mishra PK, Bhargava A, Khan S, Pathak N, Punde RP, Varshney S. Prevalence of hepatitis C virus genotypes and impact of T helper cytokines in achieving sustained virological response during combination therapy: a study from Central India. Indian J Med Microbiol. 2010;28:358–62.

    Article  PubMed  CAS  Google Scholar 

  14. Mishra PK, Khan S, Bhargava A, Panwar H, Banerjee S, Jain SK, et al. Regulation of isocyanate-induced apoptosis, oxidative stress, and inflammation in cultured human neutrophils: isocyanate-induced neutrophils apoptosis. Cell Biol Toxicol. 2010;26:279–91.

    Article  PubMed  CAS  Google Scholar 

  15. Mishra PK, Raghuram GV, Panwar H, Jain D, Pandey H, Maudar KK. Mitochondrial oxidative stress elicits chromosomal instability after exposure to isocyanates in human kidney epithelial cells. Free Radic Res. 2009;43:718–28.

    Article  PubMed  CAS  Google Scholar 

  16. Bhargava A, Punde RP, Pathak N, Dabadghao S, Desikan P, Jain A, et al. Status of inflammatory biomarkers in the population that survived the Bhopal gas tragedy: a study after two decades. Ind Health. 2010;48:204–8.

    Article  PubMed  CAS  Google Scholar 

  17. Bhargava A, Khan S, Panwar H, Pathak N, Punde RP, Varshney S, et al. Occult hepatitis B virus infection with low viremia induces DNA damage, apoptosis and oxidative stress in peripheral blood lymphocytes. Virus Res. 2010;153:143–50.

    Article  PubMed  CAS  Google Scholar 

  18. Mishra PK, Dabadghao S, Modi GK, Desikan P, Jain A, Mittra I, et al. In utero exposure to methyl isocyanate in the Bhopal gas disaster: evidence of persisting hyperactivation of immune system two decades later. Occup Environ Med. 2009;66:279.

    Article  PubMed  CAS  Google Scholar 

  19. Alacacioglu A, Somali I, Simsek I, Astarcioglu I, Ozkan M, Camci C, et al. Epidemiology and survival of hepatocellular carcinoma in Turkey: outcome of multicenter study. Jpn J Clin Oncol. 2008;38:683–8.

    Article  PubMed  Google Scholar 

  20. Fan XG, Yakkob J, Fan XJ, Keeling PW. Enhanced Th2 responses: immune mechanism of H. pylori infection. Ir J Med Sci. 1996;165:37–9.

    Article  PubMed  CAS  Google Scholar 

  21. Jirillo E, Greco B, Caradonna L, Satalino R, Pugliese V, Cozzolongo R, et al. Evaluation of cellular immune responses and soluble mediators in patients with chronic hepatitis C virus (cHCV) infection. Immunopharmacol Immunotoxicol. 1995;17:347–64.

    Article  PubMed  CAS  Google Scholar 

  22. Cacciarelli TV, Martinez OM, Gish RG, Villanueva JC, Krams SM. Immunoregulatory cytokines in chronic hepatitis C virus infection: pre-and post treatment with interferon alfa. Hepatology. 1996;24:6–9.

    Article  PubMed  CAS  Google Scholar 

  23. Piazzolla G, Tortorella C, Schiraldi O, Antonaci S. Relationship between interferon-gamma, interleukin-10, and interleukin-12 production in chronic hepatitis C and in vitro effects of interferon-alpha. J Clin Immunol. 2000;20:54–61.

    Article  PubMed  CAS  Google Scholar 

  24. Song LH, Binh VQ, Dinh ND, Kun JF, Bock TC, Kremsner PG, et al. Serum cytokine profiles associated with clinical presentation in Vietnamese infected with hepatitis B virus. J Clin Virol. 2003;28:93–103.

    Article  CAS  Google Scholar 

  25. Clerici M, Shearer GM. TH1-TH2 switch is a critical step in the etiology of HIV infection. Immunol Today. 1993;14:107–10.

    Article  PubMed  CAS  Google Scholar 

  26. Hsia CY, Huo TI, Chiang SY, Lu MF, Sun CL, Wu JC, et al. Evaluation of interleukin-6, interleukin-10 and human hepatocyte growth factor as tumor markers for hepatocellular carcinoma. Eur J Surg Oncol. 2007;33:208–12.

    PubMed  Google Scholar 

  27. Pepys MB, Hirschfield GM. C-reactive protein: a critical update. J Clin Invest. 2003;111:1805–12.

    PubMed  CAS  Google Scholar 

  28. Shrive AK, Cheetham GM, Holden D, Myles DA, Turnell WG, Volanakis JE, et al. Three dimensional structure of human C-reactive protein. Nat Struct Biol. 1996;3:346–54.

    Article  PubMed  CAS  Google Scholar 

  29. Frank R, Hargreaves R. Clinical biomarkers in drug discovery and development. Nat Rev Drug Discov. 2003;2:566–80.

    Article  PubMed  CAS  Google Scholar 

  30. Black S, Kushner I, Samols D. C-reactive protein. J Biol Chem. 2004;279:48487–90.

    Article  PubMed  CAS  Google Scholar 

  31. Clearfield MB. C-reactive protein: a new risk assessment tool for cardiovascular disease. J Am Osteopath Assoc. 2005;105:409–16.

    PubMed  Google Scholar 

  32. Di Napoli M, Papa F. C-reactive protein and cerebral small-vessel disease: an opportunity to reassess small-vessel disease physiopathology? Circulation. 2005;112:781–5.

    Article  PubMed  Google Scholar 

  33. Lin ZY, Wang LY, Yu ML, Chen SC, Chuang WL, Hsieh MY, et al. Role of serum C-reactive protein as a marker of hepatocellular carcinoma in patients with cirrhosis. J Gastroenterol Hepatol. 2000;15:417–21.

    Article  PubMed  CAS  Google Scholar 

  34. Nagaoka S, Yoshida T, Akiyoshi J, Akiba J, Torimura T, Adachi H, et al. Serum C-reactive protein levels predict survival in hepatocellular carcinoma. Liver Int. 2007;27:1091–7.

    Article  PubMed  CAS  Google Scholar 

  35. Patel T. Apoptosis in hepatic pathophysiology. Clin Liver Dis. 2000;4:295–317.

    Article  PubMed  CAS  Google Scholar 

  36. Liu DX. A new hypothesis of pathogenetic mechanism of viral hepatitis B and C. Med Hypotheses. 2001;56:405–8.

    Article  PubMed  CAS  Google Scholar 

  37. Holdenrieder S, Eichhorn P, Beuers U, Samtleben W, Schoenermarck U, Zachoval R, et al. Nucleosomal DNA fragments in autoimmune diseases. Ann N Y Acad Sci. 2006;1075:318–27.

    Article  PubMed  CAS  Google Scholar 

  38. Swietek K, Juszczyk JJ. Reduced glutathione concentration in erythrocytes of patients with acute and chronic viral hepatitis. J Viral Hepat. 1997;4:139–41.

    PubMed  CAS  Google Scholar 

  39. Halliwell B, Gutteridge JMC. Free radicals in biology and medicine. 3rd ed. Oxford: Science Publications; 1999.

    Google Scholar 

  40. Chrobot AM, Szaflarska-Szczepanik A, Drewa G. Antioxidant defense in children with chronic viral hepatitis B and C. Med Sci Monit. 2000;6:713–8.

    PubMed  CAS  Google Scholar 

  41. Tanyalcin T, Taskiran D, Topalak O, Batur Y, Kutay F. The effects of chronic hepatitis C and B virus infections on liver reduced and oxidized glutathione concentrations. Hepatol Res. 2000;18:104–9.

    Article  PubMed  Google Scholar 

  42. Demirdag K, Yilmaz S, Ozdarendeli A, Ozden M, Kalkan A, Kilic SS. Levels of plasma malondialdehyde and erythrocyte antioxidant enzyme activities in patients with chronic hepatitis B. Hepatogastroenterology. 2003;50:766–70.

    PubMed  CAS  Google Scholar 

  43. Maki A, Kono H, Gupta M, Asakawa M, Suzuki T, Matsuda M, et al. Predictive power of biomarkers of oxidative stress and inflammation in patients with hepatitis C virus-associated hepatocellular carcinoma. Ann Surg Oncol. 2007;14:1182–90.

    Article  PubMed  Google Scholar 

Download references

Acknowledgment

The authors gratefully acknowledge financial support of the Bhopal Memorial Hospital Trust, India.

Author information

Author notes

  1. Pradyumna K. Mishra

    Present address: Division of Translational Research, Tata Memorial Centre, ACTREC, Navi Mumbai, 410 210, India

Authors and Affiliations

  1. Bhopal Memorial Hospital & Research Centre, Bhopal, India

    Saba Khan, Arpit Bhargava, Neelam Pathak, Kewal. K. Maudar, Subodh Varshney & Pradyumna K. Mishra

  2. Division of Translational Research, Tata Memorial Centre, ACTREC, Navi Mumbai, 410 210, India

    Arpit Bhargava

Authors
  1. Saba Khan
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Arpit Bhargava
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Neelam Pathak
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Kewal. K. Maudar
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Subodh Varshney
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Pradyumna K. Mishra
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Pradyumna K. Mishra.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Khan, S., Bhargava, A., Pathak, N. et al. Circulating Biomarkers and their Possible Role in Pathogenesis of Chronic Hepatitis B and C Viral Infections. Ind J Clin Biochem 26, 161–168 (2011). https://doi.org/10.1007/s12291-010-0098-7

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12291-010-0098-7

Keywords

Search

Navigation