Advertisement

Endocrine Manifestations of HCV-Positive Cryoglobulinemia

  • Alessandro Antonelli
  • Clodoveo Ferri
  • Silvia Martina Ferrari
  • Michele Colaci
  • Alda Corrado
  • Andrea Di Domenicantonio
  • Poupak Fallahi
Chapter

Abstract

Hepatitis C virus (HCV) is known to be responsible for both hepatic and extrahepatic diseases. Among systemic HCV-related extrahepatic diseases (HCV-EHDs), mixed cryoglobulinemia (MC) has been extensively studied. More recently, an increased prevalence of endocrine disorders has been observed in a large series of HCV-infected patients with MC. The most frequent and clinically important endocrine disorders in MC are thyroid disorders and type 2 diabetes mellitus (T2D). A significant association between MC and thyroid autoimmunity and hypothyroidism has been shown. A high prevalence of thyroid cancer has also been reported. Furthermore, several clinical epidemiologic studies demonstrated that MC is associated to T2D. An increasing number of studies have linked a Th1 immune response with HCV infection, MC, autoimmune thyroid disorders, and diabetes. These data suggest a common immunological Th1 pattern as the pathophysiological basis of the association.

Keywords

Thyroid Cancer Thyroid Papillary Cancer Autoimmune Thyroiditis Mixed Cryoglobulinemia Autoimmune Thyroid Disorder 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

References

  1. 1.
    Ferri C, Antonelli A, Mascia MT et al (2007) B-cells and mixed cryoglobulinemia. Autoimmun Rev 7:114–120PubMedCrossRefGoogle Scholar
  2. 2.
    Sansonno D, Carbone A, De Re V et al (2007) Hepatitis C virus infection, cryoglobulinaemia, and beyond. Rheuma­tology (Oxford) 46:572–578CrossRefGoogle Scholar
  3. 3.
    Antonelli A, Ferri C, Galeazzi M et al (2008) HCV infection: pathogenesis, clinical manifestations and therapy. Clin Exp Rheumatol 26:S39–S47PubMedGoogle Scholar
  4. 4.
    Antonelli A, Ferri C, Ferrari SM et al (2008) Immuno­pathogenesis of HCV-related endocrine manifestations in chronic hepatitis and mixed cryoglobulinemia. Autoimmun Rev 8:18–23PubMedCrossRefGoogle Scholar
  5. 5.
    Antonelli A, Ferri C, Fallahi P et al (2006) Thyroid disorders in chronic hepatitis C virus infection. Thyroid 16:563–572PubMedCrossRefGoogle Scholar
  6. 6.
    Antonelli A, Ferri C, Pampana A et al (2004) Thyroid disorders in chronic hepatitis C. Am J Med 117:10–13PubMedCrossRefGoogle Scholar
  7. 7.
    Antonelli A, Ferri C, Fallahi P et al (2004) Thyroid involvement in patients with overt HCV-related mixed cryoglobulinaemia. QJM 97:499–506PubMedCrossRefGoogle Scholar
  8. 8.
    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 297:2010–2017PubMedCrossRefGoogle Scholar
  9. 9.
    Antonelli A, Ferri C, Ferrari SM et al (2009) Endocrine manifestations of hepatitis C virus infection. Nat Clin Pract Endocrinol Metab 5:26–34PubMedCrossRefGoogle Scholar
  10. 10.
    Antonelli A, Ferri C, Fallahi P (2009) Hepatitis C: thyroid dysfunction in patients with hepatitis C on IFN-alpha therapy. Nat Rev Gastroenterol Hepatol 6:633–635PubMedCrossRefGoogle Scholar
  11. 11.
    Gowans EJ (2000) Distribution of markers of hepatitis C virus infection throughout the body. Semin Liver Dis 20:85–102PubMedCrossRefGoogle Scholar
  12. 12.
    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 80:1588–1594PubMedCrossRefGoogle Scholar
  13. 13.
    Prummel MF, Laurberg P (2003) Interferon-alpha and autoimmune thyroid disease. Thyroid 13:547–551PubMedCrossRefGoogle Scholar
  14. 14.
    Apolinario A, Majano PL, Lorente R et al (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 12:27–37PubMedCrossRefGoogle Scholar
  15. 15.
    Antonelli A, Rotondi M, Fallahi P et al (2004) High levels of circulating CXCL10 are associated with chronic autoimmune thyroiditis and hypothyroidism. J Clin Endocrinol Metab 89:5496–5499PubMedCrossRefGoogle Scholar
  16. 16.
    Antonelli A, Rotondi M, Fallahi P et al (2005) Increase of interferon-gamma inducible alpha chemokine CXCL10 but not beta chemokine CCL2 serum levels in chronic autoimmune thyroiditis. Eur J Endocrinol 152:171–177PubMedCrossRefGoogle Scholar
  17. 17.
    Antonelli A, Rotondi M, Ferrari SM et al (2006) Interferon-gamma-inducible alpha-chemokine CXCL10 involvement in Graves’ ophthalmopathy: modulation by peroxisome proliferator-activated receptor-gamma agonists. J Clin Endocrinol Metab 9:614–620Google Scholar
  18. 18.
    Antonelli A, Ferri C, Fallahi P et al (2008) High values of CXCL10 serum levels in patients with hepatitis C associated mixed cryoglobulinemia in presence or absence of autoimmune thyroiditis. Cytokine 42:137–143PubMedCrossRefGoogle Scholar
  19. 19.
    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 57:1270–1277PubMedCrossRefGoogle Scholar
  20. 20.
    Antonelli A, Ferri C, Fallahi P (1999) Thyroid cancer in patients with hepatitis C infection. JAMA 281:1588PubMedCrossRefGoogle Scholar
  21. 21.
    Antonelli A, Ferri C, Fallahi P et al (2002) Thyroid cancer in HCV-related mixed cryoglobulinemia patients. Clin Exp Rheumatol 20:693–696PubMedGoogle Scholar
  22. 22.
    Antonelli A, Ferri C, Fallahi P et al (2007) Thyroid cancer in HCV-related chronic hepatitis patients: a case-control study. Thyroid 17:447–451PubMedCrossRefGoogle Scholar
  23. 23.
    Okayasu I, Fujiwara M, Hara Y et al (1995) Association of chronic lymphocytic thyroiditis and thyroid papillary carcinoma: a study of surgical cases among Japanese, and white and African Americans. Cancer 76:2313–2318CrossRefGoogle Scholar
  24. 24.
    Noto H, Raskin P (2006) Hepatitis C infection and diabetes. J Diabetes Complications 20:113–120PubMedCrossRefGoogle Scholar
  25. 25.
    Antonelli A, Ferri C, Fallahi P et al (2005) Hepatitis C virus infection: evidence for an association with type 2 diabetes. Diabetes Care 28:2548–2550PubMedCrossRefGoogle Scholar
  26. 26.
    Antonelli A, Ferri C, Fallahi P et al (2004) Type 2 diabetes in hepatitis C-related mixed cryoglobulinaemia patients. Rheumatology (Oxford) 43:238–240CrossRefGoogle Scholar
  27. 27.
    Mehta SH, Brancati FL, Sulkowski MS et al (2000) Prevalence of type 2 diabetes mellitus among persons with hepatitis C virus infection in the United States. Ann Intern Med 133:592–599PubMedCrossRefGoogle Scholar
  28. 28.
    Mehta SH, Brancati FL, Strathdee SA et al (2003) Hepatitis C virus infection and incident type 2 diabetes. Hepatology 38:50–56PubMedCrossRefGoogle Scholar
  29. 29.
    Tanaka H, Shiota G, Kawasaki H (1997) Changes in glucose tolerance after interferon-alpha therapy in patients with chronic hepatitis C. J Med 28:335–346PubMedGoogle Scholar
  30. 30.
    Giordanino C, Bugianesi E, Smedile A et al (2008) Incidence of type 2 diabetes mellitus and glucose abnormalities in patients with chronic hepatitis c infection by response to treatment: results of a cohort study. Am J Gastroenterol 103:2481–2487PubMedCrossRefGoogle Scholar
  31. 31.
    Masini M, Campani D, Boggi U et al (2005) Hepatitis C virus infection and human pancreatic beta-cell dysfunction. Diabetes Care 28:940–941PubMedCrossRefGoogle Scholar
  32. 32.
    Skowronski M, Zozulinska D, Juszczyk J et al (2006) Hepatitis C virus infection: evidence for an association with type 2 diabetes. Diabetes Care 29:750PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Italia 2012

Authors and Affiliations

  • Alessandro Antonelli
    • 1
  • Clodoveo Ferri
    • 2
  • Silvia Martina Ferrari
    • 1
  • Michele Colaci
    • 2
  • Alda Corrado
    • 1
  • Andrea Di Domenicantonio
    • 1
  • Poupak Fallahi
    • 1
  1. 1.Metabolism Unit, Department of Internal MedicineUniversity of Pisa School of MedicinePisaItaly
  2. 2.Rheumatology Unit, Department of Internal MedicineUniversity of Modena and Reggio Emilia, Medical SchoolModenaItaly

Personalised recommendations