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Thyroid involvement in hepatitis C — Associated mixed cryoglobulinemia

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Abstract

OBJECTIVE

The prevalence and clinical features of thyroid involvement in patients with hepatitis C virus-associated mixed cryoglobulinemia (MC + HCV) have been reviewed.

DESIGN

A PubMed Medline search was conducted through December 2011 to identify all studies that reported thyroid involvement in MC + HCV patients. Reference lists of the papers initially detected were manually searched to identify additional relevant reports. Studies had to contain sufficient and clear information to be included.

RESULTS

In MC+HCV patients, the following thyroid autoimmune abnormalities were significantly more frequent than in controls: high levels of serum anti-thyroperoxidase autoantibody (AbTPO); high levels of serum AbTPO and/or anti-thyroglobulin autoantibody; humoral and ultrasonographical signs of thyroid autoimmunity (35% vs 16%); prevalence of subclinical hypothyroidism (11% vs 2%). Also, the prevalence of papillary thyroid cancer has been found higher in MC + HCV patients than in controls, in particular in patients with autoimmune thyroiditis. The involvement of T helper 1 immunity and chemokine (C-X-C motif) ligand 10 (CXCL10) may be the pathogenetic basis of the association between MC + HCV and thyroid autoimmunity.

CONCLUSION

These results show a high prevalence of thyroid disorders in patients with MC + HCV and point to the need for careful monitoring of thyroid function in these patients.

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References

  1. Pateron D, Hartmann DJ, Duclos-Vallee JC, Jouanolle H, Beaugrand M, 1992 Latent autoimmune thyroid disease in patients with chronic HCV hepatitis. J Hepatol 16: 244–245.

    Article  CAS  PubMed  Google Scholar 

  2. Antonelli A, Fern C, Fallahi P, et al, 2006 Thyroid disorders in chronic hepatitis C virus infection. Thyroid 16: 563–572.

    Article  PubMed  Google Scholar 

  3. Antonelli A, Ferri C, Ferrari SM, Colaci M, Sansonno D, Fallahi P, 2009 Endocrine manifestations of hepatitis C virus infection. Nat Clin Pract Endocrinol Metab 5: 26–34.

    Article  CAS  PubMed  Google Scholar 

  4. Antonelli A, Ferri C, Galeazzi M, et al, 2008 HCV infection: pathogenesis, clinical manifestations and therapy. Clin Exp Rheumatol 26: S39–47.

    PubMed  CAS  Google Scholar 

  5. Giordano TP, Henderson L, Landgren O, et al, 2007 Risk of non-Hodgkin lymphoma and lymphoproliferative precursor diseases in US veterans with hepatitis C virus. JAMA 297: 2010–2017.

    Article  CAS  PubMed  Google Scholar 

  6. Codes L, de Freitas LA, Santos-Jesus R, et al, 2003 Comparative study of hepatitis C virus genotypes 1 and 3 in Salvador, Bahia Brazil. Braz J Infect Dis 7: 409–417.

    Article  CAS  PubMed  Google Scholar 

  7. Zarebska-Michaluk DA, Lebensztejn DM, Kryczka WM, Skiba E, 2010 Extrahepatic manifestations associated with chronic hepatitis C infections in Poland. Adv Med Sci 55: 67–73.

    Article  CAS  PubMed  Google Scholar 

  8. Goldman M, Lambert P, Tasiaux N, et al, 1987 Thyroid-stimulating immunoglobulins in mixed (type II) cryoglobulinemia associated with thyrotoxicosis. Arthritis Rheum 30: 1318–1319.

    Article  CAS  PubMed  Google Scholar 

  9. Castellano Higuera A, Gonzáles Reimers E, Alarcó Hernández B, Santolaria Fernández F, Rodríguez Gaspar M, 2003 Hypothyroidism, hemolytic anemia and cryoglobulinemia in a patient with hepatitis C virus infection: efficacy of treatment with alpha-interferon. An Med Interna 20: 391–392.

    PubMed  CAS  Google Scholar 

  10. Antonelli A, Ferri C, Fallahi P, et al, 2004 Thyroid involvement in patients with overt HCV-related mixed cryoglobulinaemia. QJM 97: 499–506.

    Article  CAS  PubMed  Google Scholar 

  11. Antonelli A, Ferri C, Fallahi P, 1999 Thyroid cancer in patients with hepatitis C infection. JAMA 281: 1588.

    Article  CAS  PubMed  Google Scholar 

  12. Montella M, Crispo A, Pezzullo L, et al, 2000 Is hepatitis C virus infection associated with thyroid cancer? A case-control study. Int J Cancer 87: 611–612.

    Article  CAS  PubMed  Google Scholar 

  13. Montella M, Crispo A, de Bellis G, et al, 2001 HCV and cancer: a case-control study in a high-endemic area. Liver 21: 335–341.

    Article  CAS  PubMed  Google Scholar 

  14. Antonelli A, Ferri C, Fallahi P, et al, 2007 Thyroid cancer in HCV-related chronic hepatitis patients: a case-control study. Thyroid 17: 447–451.

    Article  CAS  PubMed  Google Scholar 

  15. Antonelli A, Ferri C, Fallahi P, Nesti C, Zignego AL, Maccheroni M, 2002 Thyroid cancer in HCV-related mixed cryoglobulinemia patients. Clin Exp Rheumatol 20: 693–696.

    PubMed  CAS  Google Scholar 

  16. Fiore E, Rago T, Latrofa F, et al, 2011 Hashimoto’s thyroiditis is associated with papillary thyroid carcinoma: role of TSH and of treatment with L-thyroxine. Endocr Relat Cancer 18: 429–437.

    Article  CAS  PubMed  Google Scholar 

  17. Antonelli A, Bocci G, La Motta C, et al, 2011 Novel pyrazolopyrimidine derivatives as tyrosine kinase inhibitors with antitumoral activity in vitro and in vivo in papillary dedifferentiated thyroid cancer. J Clin Endocrinol Metab 96: E288–296.

    Article  CAS  PubMed  Google Scholar 

  18. Okayasu I, Fujiwara M, Hara Y, Tanaka Y, Rose NR, 1995 Association of chronic lymphocytic thyroiditis and thyroid papillary carcinoma: a study of surgical cases among Japanese, and white and African Americans. Cancer 76: 2313–2318.

    Article  Google Scholar 

  19. Ferri C, Antonelli A, Mascia MT, et al, 2007 HCV-related autoimmune and neoplastic disorders: the HCV syndrome. Dig Liver Dis 39 Suppl 1:S13–21.

    Article  PubMed  Google Scholar 

  20. Tomer Y, Blackard JT, Akeno N, 2007 Interferon alpha treatment and thyroid dysfunction. Endocrinol Metab Clin North Am 36: 1051–1066.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Vezali E, Elefsiniotis I, Mihas C, Konstantinou E, Saroglou G, 2009 Thyroid dysfunction in patients with chronic hepatitis C: virus- or therapy-related? J Gastroenterol Hepatol 24: 1024–1029.

    Article  CAS  PubMed  Google Scholar 

  22. Papo T, Oksenhendler E, Izembart M, Leger A, Clauvel JP, 1992 Antithyroid hormone antibodies induced by interferon-alpha. J Clin Endocrinol Metab 75: 1484–1486.

    PubMed  CAS  Google Scholar 

  23. Mazzaro C, Lacchin T, Moretti M, et al, 1995 Effects of two different alpha-interferon regimens on clinical and virological findings in mixed cryoglobulinemia. Clin Exp Rheumatol S13: 181–185.

    Google Scholar 

  24. Antonelli A, Ferri C, Ferrari SM, Colaci M, Fallahi P, 2008 Immunopathogenesis of HCV-related endocrine manifestations in chronic hepatitis and mixed cryoglobulinemia. Autoimmun Rev 8: 18–23.

    Article  CAS  PubMed  Google Scholar 

  25. Mihm S, Schweyer S, Ramadori G, 2003 Expression of the chemokine IP-10 correlates with the accumulation of hepatic IFN-gamma and IL-18 mRNA in chronic hepatitis C but not in hepatitis B. J Med Virol 70: 562–570.

    Article  CAS  PubMed  Google Scholar 

  26. Apolinario A, Majano PL, Lorente R, Núñez O, Clemente G, García-Monzón C, 2005 Gene expression profile of T-cell-specific chemokines in human hepatocyte-derived cells: evidence for a synergistic inducer effect of cytokines and hepatitis C virus proteins. J Viral Hepat 12: 27–37.

    Article  CAS  PubMed  Google Scholar 

  27. Antonelli A, Rotondi M, Fallahi P, et al, 2006 Increase of interferon-gamma-inducible CXC chemokine CXCL10 serum levels in patients with active Graves’ disease, and modulation by methimazole therapy. Clin Endocrinol (Oxf) 64: 189–195.

    Article  CAS  Google Scholar 

  28. Antonelli A, Rotondi M, Fallahi P, et al, 2007 Iodine-131 Given for Therapeutic Purposes Modulates Differently Interferon-{gamma}-Inducible {alpha}-Chemokine CXCL10 serum Levels in Patients with Active Graves’ Disease or Toxic Nodular Goiter. J Clin Endocrinol Metab 92: 1485–1490.

    Article  CAS  PubMed  Google Scholar 

  29. Antonelli A, Fallahi P, Rotondi M, Ferrari SM, Serio M, Miccoli P, 2006 Serum levels of the interferon-gamma-inducible alpha chemokine CXCL10 in patients with active Graves’ disease, and modulation by methimazole therapy and thyroidectomy. Br J Surg 93: 1226–1231.

    Article  CAS  PubMed  Google Scholar 

  30. Antonelli A, Fallahi P, Nesti C, et al, 2001 Anti-CD38 autoimmunity in patients with chronic autoimmune thyroiditis or Graves’ disease. Clin Exp Immunol 126: 426–431.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Gowans EJ, 2000 Distribution of markers of hepatitis C virus infection throughout the body. Semin Liver Dis 20: 85–102.

    Article  CAS  PubMed  Google Scholar 

  32. Bartolomé J, Rodríguez-Iñigo E, Quadros P, et al, 2008 Detection of hepatitis C virus in thyroid tissue from patients with chronic HCV infection. J Med Virol 80: 1588–1594.

    Article  CAS  PubMed  Google Scholar 

  33. Blackard JT, Kong L, Huber AK, Tomer Y, 2012 Hepatitis C virus infection of a thyroid cell line: implications for pathogenesis of HCV and thyroiditis. Thyroid 23: 863–870.

    Article  CAS  Google Scholar 

  34. Antonelli A, Ferri C, Fallahi P, et al, 2008 Alpha-chemokine CXCL10 and beta-chemokine CCL2 serum levels in patients with hepatitis C-associated cryoglobulinemia in the presence or absence of autoimmune thyroiditis. Metabolism 57: 1270–1277.

    Article  CAS  PubMed  Google Scholar 

  35. Antonelli A, Ferri C, Ferrari SM, et al, 2011 The presence of autoimmune thyroiditis in mixed cryoglobulinemia patients is associated with high levels of circulating interleukin-6, but not of tumor necrosis factor-alpha. Clin Exp Rheumatol 29: S17–22.

    PubMed  Google Scholar 

  36. Antonelli A, Ferri C, Ferrari SM, et al, 2010 Interleukin-1β, C-x-C motif ligand 10, and interferon-gamma serum levels in mixed cryoglobulinemia with or without autoimmune thyroiditis. J Int Cyt Res 30: 835–842.

    Article  CAS  Google Scholar 

  37. Ferri C, Antonelli A, Mascia MT, et al, 2007 B-cells and mixed cryoglobulinemia. Autoimmun Rev 7: 114–120.

    Article  CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Department of Clinical and Experimental Medicine, University of Pisa, Via Savi, 10, I-56126, Pisa, Italy

    Poupak Fallahi, Silvia Martina Ferrari, Caterina Mancusi, Silvia Fabiani & Alessandro Antonelli MD

  2. Department of Medical, Surgical, Maternal, Pediatric and Adult Sciences, University of Modena and Reggio Emilia, Modena, Italy

    Dilia Giuggioli, Andreina Manfredi & Clodoveo Ferri

  3. Department of Medico-Surgical Sciences and Biotechnologies, “Sapienza” University of Rome, Latina, Italy

    Marco Centanni

  4. Department of Translational Research and of New Technologies in Medicine and Surgery, University of Pisa, Pisa, Italy

    Santino Marchi

Authors
  1. Poupak Fallahi
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  2. Silvia Martina Ferrari
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  3. Dilia Giuggioli
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  4. Andreina Manfredi
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  5. Caterina Mancusi
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  6. Silvia Fabiani
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  8. Santino Marchi
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  9. Clodoveo Ferri
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  10. Alessandro Antonelli MD
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Correspondence to Alessandro Antonelli MD.

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Fallahi, P., Ferrari, S.M., Giuggioli, D. et al. Thyroid involvement in hepatitis C — Associated mixed cryoglobulinemia. Hormones 13, 16–23 (2014). https://doi.org/10.1007/BF03401317

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  • DOI: https://doi.org/10.1007/BF03401317

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