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Role of serum dehydroepiandrosterone sulfate level on the clearance of chronic hepatitis B virus infection

  • Original Article—Liver, Pancreas, and Biliary Tract
  • Published:
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Abstract

Background

The natural course of chronic hepatitis B virus (HBV) infection and relevant host factors remain unclear. This study aims to investigate the impact of dehydroepiandrosterone sulfate (DHEAS) on the clearance of chronic HBV infection.

Methods

Two hundred and one hepatitis B e antigen (HBeAg)-positive chronic HBV-infected children (101 females) were recruited. Serum DHEAS levels were determined in all subjects at 15 years of age. Serum alanine aminotransferase (ALT) levels, DHEAS levels, HBV seromarkers, genotypes, and viral loads were included for analysis.

Results

Subjects with serum DHEAS levels >3.6 μmol/L at midpuberty had earlier HBeAg seroconversion (median age, 14.7 vs. 18.2 years; HR, 1.9; P = 0.03), and the impact persisted even after adjusting for gender, HBV genotype, peak ALT levels, and viral load. Subjects with DHEAS levels >3.6 μmol/L at 15 years of age had more HBV viral titers decrement from 15 to 20 years of age (mean ± SD, 3.5 ± 2.5 vs. 1.2 ± 2.2 log10 copies/mL; P = 0.05) and shorter duration for HBeAg seroconversion than others (mean ± SD, 5.6 ± 4.4 vs. 9.2 ± 4.9 years; P = 0.02). Higher serum DHEAS levels at 15 years of age are also associated with greater hepatitis B surface antigen (HBsAg) titer decrement from 15 to 20 years of age (correlation coefficient = 0.45, P = 0.04).

Conclusions

Higher serum DHEAS levels at midpuberty predicts more HBV viral load and HBsAg titer decrement from midpuberty to young adulthood. Higher serum DHEAS levels at midpuberty also correlate with younger age of spontaneous HBeAg seroconversion in chronic genotype B and C HBV-infected patients.

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Abbreviations

ALT:

Alanine aminotransferase

DHEAS:

Dehydroepiandrosterone sulfate

HBV:

Hepatitis B virus

HBeAg:

Hepatitis B e antigen

HBsAg:

Hepatitis B surface antigen

References

  1. Beasley RP, Hwang LY, Lin CC, Chien CS. Hepatocellular carcinoma and hepatitis B virus: a prospective study of 22,707 men in Taiwan. Lancet. 1981;2:1129–33.

    Article  CAS  PubMed  Google Scholar 

  2. Liu Z, Luo K, He H, Hou J. Hot-spot mutations in hepatitis B virus core gene: eliciting or evading immune clearance? J Viral Hepat. 2005;12:146–53.

    Article  CAS  PubMed  Google Scholar 

  3. Fattovich G, Rugge M, Brollo L, Pontisso P, Noventa F, Guido M, et al. Clinical, virologic, and histologic outcome following seroconversion from HBeAg to anti-HBe in chronic hepatitis type B. Hepatology. 1986;6:167–72.

    Article  CAS  PubMed  Google Scholar 

  4. Yang HI, Lu SN, Liaw YF, You SL, Sun CA, Wang LY, et al. Hepatitis B e antigen and the risk of hepatocellular carcinoma. N Engl J Med. 2002;347:168–74.

    Article  CAS  PubMed  Google Scholar 

  5. Ni YH, Chang MH, Chen PJ, Tsai KS, Hsu HY, Chen HL, et al. Viremia profiles in children with chronic hepatitis B virus infection and spontaneous e antigen seroconversion. Gastroenterology. 2007;132:2340–5.

    Article  PubMed  Google Scholar 

  6. Tseng TC, Liu CJ, Yang HC, Su TH, Wang CC, Chen CL, et al. High levels of hepatitis B surface antigen increase risk of hepatocellular carcinoma in patients with low HBV load. Gastroenterology. 2012;142:1140–9.

    Article  CAS  PubMed  Google Scholar 

  7. Beasley RP, Trepo C, Stevens CE, Szmuness W. The e antigen and vertical transmission of hepatitis B surface antigen. Am J Epidemiol. 1977;105:94–8.

    CAS  PubMed  Google Scholar 

  8. Hsu SC, Chang MH, Ni YH, Hsu HY, Lee CY. Horizontal transmission of hepatitis B virus in children. J Pediatr Gastroenterol Nutr. 1993;16:66–9.

    Article  CAS  PubMed  Google Scholar 

  9. Wu JF, Tsai WY, Hsu HY, Ni YH, Chen HL, Tsuei DJ, et al. The effect of puberty onset on spontaneous hepatitis B virus e antigen seroconversion in men. Gastroenterology. 2010;138:942–8.

    Article  PubMed  Google Scholar 

  10. Tseng TC, Liu CJ, Su TH, Wang CC, Chen CL, Chen PJ, et al. Serum hepatitis B surface antigen levels predict surface antigen loss in hepatitis B e antigen seroconverters. Gastroenterology. 2011;141:517–25.

    Article  CAS  PubMed  Google Scholar 

  11. Shiratori Y, Shiina S, Imamura M, Kato N, Kanai F, Okudaira T, et al. Characteristic difference of hepatocellular carcinoma between hepatitis B- and C-viral infection in Japan. Hepatology. 1995;22:1027–33.

    Article  CAS  PubMed  Google Scholar 

  12. Lee CM, Lu SN, Changchien CS, Yeh CT, Hsu TT, Tang JH, et al. Age, gender, and local geographic variations of viral etiology of hepatocellular carcinoma in a hyperendemic area for hepatitis B virus infection. Cancer. 1999;86:1143–50.

    Article  CAS  PubMed  Google Scholar 

  13. Schuurs AH, Verheul HA. Effects of gender and sex steroids on the immune response. J Steroid Biochem Mol Biol. 1990;35:157–75.

    Article  CAS  Google Scholar 

  14. Tung YC, Lee JS, Tsai WY, Hsiao PH. Physiological changes of adrenal androgens in childhood. J Formos Med Assoc. 2004;103:921–4.

    CAS  PubMed  Google Scholar 

  15. Nawata H, Yanase T, Goto K, Okabe T, Nomura M, Ashida K, et al. Andropause. Horm Res. 2004;62:110–4.

    Article  CAS  PubMed  Google Scholar 

  16. Hazeldine J, Arlt W, Lord JM. Dehydroepiandrosterone as a regulator of immune cell function. J Steroid Biochem Mol Biol. 2010;120:127–36.

    Article  CAS  PubMed  Google Scholar 

  17. Chittiprol S, Kumar AM, Shetty KT, Kumar HR, Satishchandra P, Rao RS, et al. HIV-1 clade C infection and progressive disruption in the relationship between cortisol, DHEAS and CD4 cell numbers: a two-year follow-up study. Clin Chim Acta. 2009;409:4–10.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  18. de la Torre B, von Krogh G, Svensson M, Holmberg V. Blood cortisol and dehydroepiandrosterone sulfate (DHEAS) levels and CD4 T cell counts in HIV infection. Clin Exp Rheumatol. 1997;15:87–90.

    PubMed  Google Scholar 

  19. Kutlu NO, Akinci A, Sönmezgöz E, Temel I, Evliyaoğlu E. The effects of androstenediol and dehydroepiandrosterone on the immune response to BCG at puberty. J Trop Pediatr. 2003;49:181–5.

    Article  PubMed  Google Scholar 

  20. dos Santos CD, Toldo MP, do Prado Júnior JC. Trypanosoma cruzi: the effects of dehydroepiandrosterone (DHEA) treatment during experimental infection. Acta Trop. 2005;95:109–15.

    Article  PubMed  Google Scholar 

  21. Ben-Nathan D, Padgett DA, Loria RM. Androstenodiol and dehydroepiandrosterone protect mice against lethal bacterial infections and lipopolysaccharide toxicity. J Med Microbiol. 1999;48:421–31.

    Article  Google Scholar 

  22. Rasmussen KR, Martin EG, Healy MC. Effects of dehydroepiandrosterone in immune suppressed rats infected with Cryptosporidium parvum. J Parasitol. 1993;79:364–70.

    Article  CAS  PubMed  Google Scholar 

  23. Leenstra T, ter Kuile FO, Kariuki SK, Nixon CP, Oloo AJ, Kager PA, et al. Dehydroepiandrosterone sulphate levels associated with decreased malaria parasite density and increased hemoglobin concentration in pubertal girls from western Kenya. J Infect Dis. 2003;188:297–304.

    Article  CAS  PubMed  Google Scholar 

  24. Morales-Montor J, Newhouse E, Mohamed F, Baghdadi A, Damian RT. Altered levels of hypothalamic-pituitary-adrenocortical axis hormones in baboons and mice during the course of infection with Schistosoma mansoni. J Infect Dis. 2001;183:313–20.

    Article  CAS  PubMed  Google Scholar 

  25. Christeff N, Melchior JC, Mammes O, Gherbi N, Dalle MT, Nunez EA. Correlation between increase cortisol: DHEA ratio and malnutrition in HIV-positive men. Nutrition. 1999;15:534–9.

    Article  CAS  PubMed  Google Scholar 

  26. Butcher SK, Killampalli V, Lascelles D, Wang K, Alpar EK, Lord JM. Raised cortisol: DHEAS ratios in the elderly after injury: potential impact upon neutrophil function and immunity. Aging Cell. 2005;4:319–24.

    Article  CAS  PubMed  Google Scholar 

  27. Barkhausen T, Westphal BM, Pütz C, Krettek C, van Griensven M. Dehydroepiandrosterone administration modulates endothelial and neutrophil adhesion molecule expression in vitro. Crit Care. 2006;10:R109.

    Article  PubMed Central  PubMed  Google Scholar 

  28. Radford DJ, Wang K, McNelis JC, Taylor AE, Hechenberger G, Hofmann J, et al. Dehydroepiandrosterone sulfate directly activates protein kinase C-beta to increase human neutrophil superoxide generation. Mol Endocrinol. 2010;24:813–21.

    Article  CAS  PubMed  Google Scholar 

  29. Yang BC, Liu CW, Chen YC, Yu CK. Exogenous dehydroepiandrosterone modified the expression of T helper related cytokines in NZB/NZWF1 mice. Immun Investig. 1998;27:291–302.

    Article  Google Scholar 

  30. Araneo BA, Woods ML 2nd, Daynes RA. Reversal of the immunosenescent phenotype by dehydroepiandrosterone: hormone treatment provides an adjuvant effect on the immunization of aged mice with recombinant hepatitis B surface antigen. J Infect Dis. 1993;167:830–40.

    Article  CAS  PubMed  Google Scholar 

  31. Chen YC, Huang SF, Chu CM, Liaw YF. Serial HBV DNA levels in patients with persistently normal transaminase over 10 years following spontaneous HBeAg seroconversion. J Viral Hepat. 2012;19:138–46.

    Article  CAS  PubMed  Google Scholar 

  32. Liaw YF, Lau GK, Kao JH, Gane E. Hepatitis B e antigen seroconversion: a critical event in chronic hepatitis B virus infection. Dig Dis Sci. 2010;55:2727–34.

    Article  CAS  PubMed  Google Scholar 

  33. Wu JF, Su YR, Chen CH, Chen HL, Ni YH, Hsu HY, Wang JL, Chang MH. Predictive effect of serial serum alanine aminotransferase levels on spontaneous HBeAg seroconversion in chronic genotypes B and C HBV-infected children. J Pediatr Gastroenterol Nutr. 2012;54:97–100.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  34. Kao JH, Chen PJ, Lai MY, Chen DS. Hepatitis B virus genotypes and spontaneous hepatitis B e antigen seroconversion in Taiwanese hepatitis B carriers. J Med Virol. 2004;72:363–9.

    Article  CAS  PubMed  Google Scholar 

  35. Tseng YR, Wu JF, Ni YH, Chen HL, Chen CC, Wen WH, Hsu HY, Chang MH. Long term effect of maternal HBeAg on delayed HBeAg seroconversion in offspring with chronic hepatitis B infection. Liver Int. 2011;31:1373–80.

    Article  CAS  PubMed  Google Scholar 

  36. Chu CM, Liaw YF. Predictive factors for reactivation of hepatitis B following hepatitis B e antigen seroconversion in chronic hepatitis B. Gastroenterology. 2007;133:1458–65.

    Article  CAS  PubMed  Google Scholar 

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Acknowledgments

The authors thank Dr. Daw-Jean Tsuei from the Department of Pediatrics of National Taiwan University Children’s Hospital for laboratory assistance. Grant support: This work was supported by the grant from the National Science Council of Taiwan (NSC 99-2314-B-002-023-MY3).

Conflict of interest

The authors have no potential, perceived, or real conflict of interest. We declare that we have no conflict of interest.

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Authors and Affiliations

  1. Department of Pediatrics, National Taiwan University Hospital, No. 8, Chung-Shan S. Rd., Taipei, Taiwan

    Jia-Feng Wu, Wen-Yu Tsai, Yi-Ching Tung, Huey-Ling Chen, Yen-Hsuan Ni, Hong-Yuan Hsu & Mei-Hwei Chang

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  1. Jia-Feng Wu
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Correspondence to Mei-Hwei Chang.

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Wu, JF., Tsai, WY., Tung, YC. et al. Role of serum dehydroepiandrosterone sulfate level on the clearance of chronic hepatitis B virus infection. J Gastroenterol 49, 900–906 (2014). https://doi.org/10.1007/s00535-013-0831-0

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  • DOI: https://doi.org/10.1007/s00535-013-0831-0

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