Autoimmunity Highlights

, Volume 1, Issue 1, pp 23–35 | Cite as

Hepatitis C virus and autoimmunity

Review Article

Abstract

Hepatitis C virus infection is associated with several extrahepatic manifestations. About 60% of patients infected with HCV develop at least one extrahepatic manifestation. The majority of these diseases seem to be triggered through autoimmune mechanisms, such as autoantibody production, autoreactive T cells and complex autoimmune mechanisms leading to systemic autoimmune disorders. In this review we categorize these diseases into three groups according to the main pathogenetic process involved, in particular B-cell-mediated, T-cell-mediated and complex autoimmune systemic diseases.

Keywords

Hepatitis C Extrahepatic manifestations Autoimmune mechanism Mixed cryoglobulinaemia vasculitis Lymphoma 

References

  1. 1.
    Perrault M, Pecheur EI (2009) The hepatitis C virus and its hepatic environment: a toxic but finely tuned partnership. Biochem J 423:303–314PubMedGoogle Scholar
  2. 2.
    Lauer GM, Walker BD (2001) Hepatitis C virus infection. N Engl J Med 345:41–52PubMedGoogle Scholar
  3. 3.
    Cacoub P, Renou C, Rosenthal E et al (2000) Extrahepatic manifestations associated with hepatitis C virus infection. A prospective multicenter study of 321 patients. The GERMIVIC. Groupe d’Etude et de Recherche en Medecine Interne et Maladies Infectieuses sur le Virus de l’Hepatite C. Medicine (Baltimore) 79:47–5Google Scholar
  4. 4.
    Niewold TB, Swedler WI (2005) Systemic lupus erythematosus arising during interferon-alpha therapy for cryoglobulinemic vasculitis associated with hepatitis C. Clin Rheumatol 24:178–181PubMedGoogle Scholar
  5. 5.
    Beuthien W, Mellinghoff HU, Kempis J (2005) Vasculitic complications of interferon-alpha treatment for chronic hepatitis C virus infection: case report and review of the literature. Clin Rheumatol 24:507–515PubMedGoogle Scholar
  6. 6.
    McColl MD, Singer IO, Tait RC et al (1997) The role of hepatitis C virus in the aetiology of non-Hodgkin’s lymphoma — a regional association? Leuk Lymphoma 26:127–130PubMedGoogle Scholar
  7. 7.
    Matsuo K, Kusano A, Sugumar A et al (2004) Effect of hepatitis C virus infection on the risk of non-Hodgkin’s lymphoma: a meta-analysis of epidemiological studies. Cancer Sci 95:745–752PubMedGoogle Scholar
  8. 8.
    Ferri C (2008) Mixed cryoglobulinemia. Orphanet J Rare Dis 3:25PubMedPubMedCentralGoogle Scholar
  9. 9.
    Benoist C, Mathis D (1998) Autoimmunity. The pathogen connection. Nature 394:227–228PubMedGoogle Scholar
  10. 10.
    Fournie GJ, Mas M, Cautain B et al (2001) Induction of autoimmunity through bystander effects. Lessons from immunological disorders induced by heavy metals. J Autoimmun 16:319–326PubMedGoogle Scholar
  11. 11.
    Gregorio GV, Choudhuri K, Ma Y et al (2003) Mimicry between the hepatitis C virus polyprotein and antigenic targets of nuclear and smooth muscle antibodies in chronic hepatitis C virus infection. Clin Exp Immunol 133:404–413PubMedPubMedCentralGoogle Scholar
  12. 12.
    Akeno N, Blackard JT, Tomer Y (2008) HCV E2 protein binds directly to thyroid cells and induces IL-8 production: a new mechanism for HCV induced thyroid autoimmunity. J Autoimmun 31:339–344PubMedPubMedCentralGoogle Scholar
  13. 13.
    Ferri C, Antonelli A, Mascia MT et al (2007) B-cells and mixed cryoglobulinemia. Autoimmun Rev 7:114–120PubMedGoogle Scholar
  14. 14.
    Ducoulombier D, Roque-Afonso AM, Di Liberto G et al (2004) Frequent compartmentalization of hepatitis C virus variants in circulating B cells and monocytes. Hepatology 39:817–825PubMedGoogle Scholar
  15. 15.
    Ferri S, Muratori L, Lenzi M et al (2008) HCV and autoimmunity. Curr Pharm Des 14:1678–1685PubMedGoogle Scholar
  16. 16.
    Boyer O, Saadoun D, Abriol J et al (2004) CD4+CD25+ regulatory T-cell deficiency in patients with hepatitis C-mixed cryoglobulinemia vasculitis. Blood 103:3428–3430PubMedGoogle Scholar
  17. 17.
    Antonelli A, Ferri C, Ferrari SM et al (2008) Immunopathogenesis of HCV-related endocrine manifestations in chronic hepatitis and mixed cryoglobulinemia. Autoimmun Rev 8:18–23PubMedGoogle Scholar
  18. 18.
    Pileri P, Uematsu Y, Campagnoli S et al (1998) Binding of hepatitis C virus to CD81. Science 282:938–941PubMedGoogle Scholar
  19. 19.
    Pena LR, Nand S, De Maria N et al (2000) Hepatitis C virus infection and lymphoproliferative disorders. Dig Dis Sci 45:1854–1860PubMedGoogle Scholar
  20. 20.
    Toubi E, Gordon S, Kessel A et al (2006) Elevated serum Blymphocyte activating factor (BAFF) in chronic hepatitis C virus infection: association with autoimmunity. J Autoimmun 27:134–139PubMedGoogle Scholar
  21. 21.
    Carter RH, Fearon DT (1992) CD19: lowering the threshold for antigen receptor stimulation of B lymphocytes. Science 256:105–107PubMedGoogle Scholar
  22. 22.
    Deng J, DeKruyff RH, Freeman GJ et al (2002) Critical role of CD81 in cognate T-B cell interactions leading to Th2 responses. Int Immunol 14:513–523PubMedGoogle Scholar
  23. 23.
    Agnello V, De Rosa FG (2004) Extrahepatic disease manifestations of HCV infection: some current issues. J Hepatol 40:341–352PubMedGoogle Scholar
  24. 24.
    Zignego AL, Brechot C (1999) Extrahepatic manifestations of HCV infection: facts and controversies. J Hepatol 31:369–376PubMedGoogle Scholar
  25. 25.
    Zignego AL, Giannelli F, Marrocchi ME et al (2000) T(14;18) translocation in chronic hepatitis C virus infection. Hepatology 31:474–479PubMedGoogle Scholar
  26. 26.
    McDonnell TJ, Korsmeyer SJ (1991) Progression from lymphoid hyperplasia to high-grade malignant lymphoma in mice transgenic for the t(14;18). Nature 349:254–256PubMedGoogle Scholar
  27. 27.
    Ellis M, Rathaus M, Amiel A et al (1995) Monoclonal lymphocyte proliferation and bcl-2 rearrangement in essential mixed cryoglobulinaemia. Eur J Clin Invest 25:833–837PubMedGoogle Scholar
  28. 28.
    Brouet JC, Clauvel JP, Danon F et al (1974) Biologic and clinical significance of cryoglobulins. A report of 86 cases. Am J Med 57:775–788Google Scholar
  29. 29.
    Misiani R, Bellavita P, Fenili D et al (1992) Hepatitis C virus infection in patients with essential mixed cryoglobulinemia. Ann Intern Med 117:573–577PubMedGoogle Scholar
  30. 30.
    Saadoun D, Landau DA, Calabrese LH et al (2007) Hepatitis Cassociated mixed cryoglobulinaemia: a crossroad between autoimmunity and lymphoproliferation. Rheumatology (Oxford) 46:1234–1242Google Scholar
  31. 31.
    Sene D, Ghillani-Dalbin P, Thibault V et al (2004) Longterm course of mixed cryoglobulinemia in patients infected with hepatitis C virus. J Rheumatol 31:2199–2206PubMedGoogle Scholar
  32. 32.
    Pawlotsky JM, Ben Yahia M, Andre C et al (1994) Immunological disorders in C virus chronic active hepatitis: a prospective case-control study. Hepatology 19:841–848PubMedGoogle Scholar
  33. 33.
    Meltzer M, Franklin EC, Elias K et al (1966) Cryoglobulinemia — a clinical and laboratory study. II. Cryoglobulins with rheumatoid factor activity. Am J Med 40:837–856PubMedGoogle Scholar
  34. 34.
    Sansonno D, Cornacchiulo V, Iacobelli AR et al (1995) Localization of hepatitis C virus antigens in liver and skin tissues of chronic hepatitis C virus-infected patients with mixed cryoglobulinemia. Hepatology 21:305–312PubMedGoogle Scholar
  35. 35.
    Sansonno D, Carbone A, De Re V et al (2007) Hepatitis C virus infection, cryoglobulinaemia, and beyond. Rheumatology (Oxford) 46:572–578Google Scholar
  36. 36.
    Ferri C, Mannini L, Bartoli V et al (1990) Blood viscosity and filtration abnormalities in mixed cryoglobulinemia patients. Clin Exp Rheumatol 8:271–281PubMedGoogle Scholar
  37. 37.
    Ramos-Casals M, Forns X, Brito-Zeron P et al (2007) Cryoglobulinaemia associated with hepatitis C virus: influence of HCV genotypes, HCV-RNA viraemia and HIV coinfection. J Viral Hepat 14:736–742PubMedGoogle Scholar
  38. 38.
    Fadda P, La Civita L, Zignego AL et al (2002) Hepatitis C virus infection and arthritis. A clinico-serological investigation of arthritis in patients with or without cryoglobulinemic syndrome (in Italian). Reumatismo 54:316–323PubMedGoogle Scholar
  39. 39.
    Cacoub P, Saadoun D, Limal N et al (2005) Hepatitis C virus infection and mixed cryoglobulinaemia vasculitis: a review of neurological complications. AIDS 19Suppl 3:S128–S134PubMedGoogle Scholar
  40. 40.
    Alpa M, Ferrero B, Cavallo R et al (2008) Anti-neuronal antibodies in patients with HCV-related mixed cryoglobulinemia. Autoimmun Rev 8:56–58PubMedGoogle Scholar
  41. 41.
    Ammendola A, Sampaolo S, Ambrosone L et al (2005) Peripheral neuropathy in hepatitis-related mixed cryoglobulinemia: electrophysiologic follow-up study. Muscle Nerve 31:382–385PubMedGoogle Scholar
  42. 42.
    Ferri C, Mascia MT (2006) Cryoglobulinemic vasculitis. Curr Opin Rheumatol 18:54–63PubMedGoogle Scholar
  43. 43.
    Authier FJ, Bassez G, Payan C et al (2003) Detection of genomic viral RNA in nerve and muscle of patients with HCV neuropathy. Neurology 60:808–812PubMedGoogle Scholar
  44. 44.
    Authier FJ, Pawlotsky JM, Viard JP et al (1993) High incidence of hepatitis C virus infection in patients with cryoglobulinemic neuropathy. Ann Neurol 34:749–750PubMedGoogle Scholar
  45. 45.
    Lidove O, Cacoub P, Hausfater P et al (1999) Cryoglobulinemia and hepatitis c: worsening of peripheral neuropathy after interferon alpha treatment (in French). Gastroenterol Clin Biol 23:403–406PubMedGoogle Scholar
  46. 46.
    Casato M, Saadoun D, Marchetti A et al (2005) Central nervous system involvement in hepatitis C virus cryoglobulinemia vasculitis: a multicenter case-control study using magnetic resonance imaging and neuropsychological tests. J Rheumatol 32:484–488PubMedGoogle Scholar
  47. 47.
    Tembl JI, Ferrer JM, Sevilla MT et al (1999) Neurologic complications associated with hepatitis C virus infection. Neurology 53:861–864PubMedGoogle Scholar
  48. 48.
    Kayali Z, Buckwold VE, Zimmerman B et al (2002) Hepatitis C, cryoglobulinemia, and cirrhosis: a meta-analysis. Hepatology 36:978–985PubMedGoogle Scholar
  49. 49.
    Ferri C, Bertozzi MA, Zignego AL (2002) Erectile dysfunction and hepatitis C virus infection. JAMA 288:698–699PubMedGoogle Scholar
  50. 50.
    Kraus MR, Schafer A, Bentink T et al (2005) Sexual dysfunction in males with chronic hepatitis C and antiviral therapy: interferon-induced functional androgen deficiency or depression? J Endocrinol 185:345–352PubMedGoogle Scholar
  51. 51.
    Witte L, Rupp J, Heyer P et al (2008) Fibrosing alveolitis with hepatitis C-related cryoglobulinemia (in German). Dtsch Med Wochenschr 133:709–712PubMedGoogle Scholar
  52. 52.
    Kaplanski G, Maisonobe T, Marin V et al (2005) Vascular cell adhesion molecule-1 (VCAM-1) plays a central role in the pathogenesis of severe forms of vasculitis due to hepatitis Cassociated mixed cryoglobulinemia. J Hepatol 42:334–340PubMedGoogle Scholar
  53. 53.
    Ferri C, Giuggioli D, Cazzato M et al (2003) HCV-related cryoglobulinemic vasculitis: an update on its etiopathogenesis and therapeutic strategies. Clin Exp Rheumatol 21:S78–S84PubMedGoogle Scholar
  54. 54.
    Ferri C, Zignego AL, Pileri SA (2002) Cryoglobulins. J Clin Pathol 55:4–13PubMedPubMedCentralGoogle Scholar
  55. 55.
    Vitali C, Ferri C, Nasti P et al (1994) Hypercomplementaemia as a marker of the evolution from benign to malignant B cell proliferation in patients with type II mixed cryoglobulinaemia. Br J Rheumatol 33:791–792PubMedGoogle Scholar
  56. 56.
    Mazzaro C, Zorat F, Comar C et al (2003) Interferon plus ribavirin in patients with hepatitis C virus positive mixed cryoglobulinemia resistant to interferon. J Rheumatol 30:1775–1781PubMedGoogle Scholar
  57. 57.
    Zuckerman E, Keren D, Slobodin G et al (2000) Treatment of refractory, symptomatic, hepatitis C virus related mixed cryoglobulinemia with ribavirin and interferon-alpha. J Rheumatol 27:2172–2178PubMedGoogle Scholar
  58. 58.
    Cacoub P, Lidove O, Maisonobe T et al (2002) Interferon-alpha and ribavirin treatment in patients with hepatitis C virus-related systemic vasculitis. Arthritis Rheum 46:3317–3326PubMedGoogle Scholar
  59. 59.
    Giannini C, Giannelli F, Zignego AL (2006) Association between mixed cryoglobulinemia, translocation (14;18), and persistence of occult HCV lymphoid infection after treatment. Hepatology 43:1166–1167PubMedGoogle Scholar
  60. 60.
    Sansonno D, De Re V, Lauletta G et al (2003) Monoclonal antibody treatment of mixed cryoglobulinemia resistant to interferon alpha with an anti-CD20. Blood 101:3818–3826PubMedGoogle Scholar
  61. 61.
    Zaja F, De Vita S, Mazzaro C et al (2003) Efficacy and safety of rituximab in type II mixed cryoglobulinemia. Blood 101:3827–3834PubMedGoogle Scholar
  62. 62.
    Rasul I, Shepherd FA, Kamel-Reid S et al (1999) Detection of occult low-grade B-cell non-Hodgkin’s lymphoma in patients with chronic hepatitis C infection and mixed cryoglobulinemia. Hepatology 29:543–547PubMedGoogle Scholar
  63. 63.
    Pozzato G, Mazzaro C, Crovatto M et al (1994) Low-grade malignant lymphoma, hepatitis C virus infection, and mixed cryoglobulinemia. Blood 84:3047–3053PubMedGoogle Scholar
  64. 64.
    Luppi M, Longo G, Ferrari MG et al (1998) Clinico-pathological characterization of hepatitis C virus-related B-cell non-Hodgkin’s lymphomas without symptomatic cryoglobulinemia. Ann Oncol 9:495–498PubMedGoogle Scholar
  65. 65.
    Mazzaro C, Tirelli U, Pozzato G (2005) Hepatitis C virus and non-Hodgkin’s lymphoma 10 years later. Dig Liver Dis 37:219–226PubMedGoogle Scholar
  66. 66.
    Weng WK, Levy S (2003) Hepatitis C virus (HCV) and lymphomagenesis. Leuk Lymphoma 44:1113–1120PubMedGoogle Scholar
  67. 67.
    Monti G, Pioltelli P, Saccardo F et al (2005) Incidence and characteristics of non-Hodgkin lymphomas in a multicenter case file of patients with hepatitis C virus-related symptomatic mixed cryoglobulinemias. Arch Intern Med 165:101–105PubMedGoogle Scholar
  68. 68.
    Zuckerman E, Zuckerman T (2002) Hepatitis C and B-cell lymphoma: the hemato-hepatologist linkage. Blood Rev 16:119–125PubMedGoogle Scholar
  69. 69.
    De Vita S, Sacco C, Sansonno D et al (1997) Characterization of overt B-cell lymphomas in patients with hepatitis C virus infection. Blood 90:776–782PubMedGoogle Scholar
  70. 70.
    Hermine O, Lefrere F, Bronowicki JP et al (2002) Regression of splenic lymphoma with villous lymphocytes after treatment of hepatitis C virus infection. N Engl J Med 347:89–94PubMedGoogle Scholar
  71. 71.
    Vallisa D, Bernuzzi P, Arcaini L et al (2005) Role of anti-hepatitis C virus (HCV) treatment in HCV-related, low-grade, Bcell, non-Hodgkin’s lymphoma: a multicenter Italian experience. J Clin Oncol 23:468–473PubMedGoogle Scholar
  72. 72.
    Gisbert JP, Garcia-Buey L, Pajares JM et al (2005) Systematic review: regression of lymphoproliferative disorders after treatment for hepatitis C infection. Aliment Pharmacol Ther 21:653–662PubMedGoogle Scholar
  73. 73.
    Hainsworth JD, Litchy S, Burris HA III et al (2002) Rituximab as first-line and maintenance therapy for patients with indolent non-Hodgkin’s lymphoma. J Clin Oncol 20:4261–4267PubMedGoogle Scholar
  74. 74.
    Gatselis NK, Georgiadou SP, Koukoulis GK et al (2006) Clinical significance of organ- and non-organ-specific autoantibodies on the response to anti-viral treatment of patients with chronic hepatitis C. Aliment Pharmacol Ther 24:1563–1573PubMedGoogle Scholar
  75. 75.
    Ramos-Casals M, Munoz S, Medina F et al (2009) Systemic autoimmune diseases in patients with hepatitis C virus infection: characterization of 1020 cases (the HISPAMEC Registry). J Rheumatol 36:1442–1448PubMedGoogle Scholar
  76. 76.
    Hsieh MY, Dai CY, Lee LP et al (2008) Antinuclear antibody is associated with a more advanced fibrosis and lower RNA levels of hepatitis C virus in patients with chronic hepatitis C. J Clin Pathol 61:333–337PubMedGoogle Scholar
  77. 77.
    Stroffolini T, Colloredo G, Gaeta GB et al (2004) Does an ‘autoimmune’ profile affect the clinical profile of chronic hepatitis C? An Italian multicentre survey. J Viral Hepat 11:257–262PubMedGoogle Scholar
  78. 78.
    Antonelli A, Ferri C, Pampana A et al (2004) Thyroid disorders in chronic hepatitis C. Am J Med 117:10–13PubMedGoogle Scholar
  79. 79.
    Prummel MF, Laurberg P (2003) Interferon-alpha and autoimmune thyroid disease. Thyroid 13:547–551PubMedGoogle Scholar
  80. 80.
    Zein NN, Abdulkarim AS, Wiesner RH et al (2000) Prevalence of diabetes mellitus in patients with end-stage liver cirrhosis due to hepatitis C, alcohol, or cholestatic disease. J Hepatol 32:209–217PubMedGoogle Scholar
  81. 81.
    Caronia S, Taylor K, Pagliaro L et al (1999) Further evidence for an association between non-insulin-dependent diabetes mellitus and chronic hepatitis C virus infection. Hepatology 30:1059–1063PubMedGoogle Scholar
  82. 82.
    Serfaty L, Capeau J (2009) Hepatitis C, insulin resistance and diabetes: clinical and pathogenic data. Liver Int 29Suppl 2:13–25PubMedGoogle Scholar
  83. 83.
    Fabris P, Betterle C, Greggio NA et al (1998) Insulin-dependent diabetes mellitus during alpha-interferon therapy for chronic viral hepatitis. J Hepatol 28:514–517PubMedGoogle Scholar
  84. 84.
    Lonardo A, Adinolfi LE, Petta S et al (2009) Hepatitis C and diabetes: the inevitable coincidence? Expert Rev Anti Infect Ther 7:293–308PubMedGoogle Scholar
  85. 85.
    Tahrani A, Bowler L, Singh P et al (2006) Resolution of diabetes in type 2 diabetic patient treated with IFN-alpha and ribavirin for hepatitis C. Eur J Gastroenterol Hepatol 18:291–293PubMedGoogle Scholar
  86. 86.
    Doutre MS (1999) Hepatitis C virus-related skin diseases. Arch Dermatol 135:1401–1403PubMedGoogle Scholar
  87. 87.
    Gisbert JP, Garcia-Buey L, Pajares JM et al (2003) Prevalence of hepatitis C virus infection in porphyria cutanea tarda: systematic review and meta-analysis. J Hepatol 39:620–627PubMedGoogle Scholar
  88. 88.
    Hadziyannis SJ (1998) Skin diseases associated with hepatitis C virus infection. J Eur Acad Dermatol Venereol 10:12–21PubMedGoogle Scholar
  89. 89.
    Berk DR, Mallory SB, Keeffe EB et al (2007) Dermatologic disorders associated with chronic hepatitis C: effect of interferon therapy. Clin Gastroenterol Hepatol 5:142–151PubMedGoogle Scholar
  90. 90.
    Shengyuan L, Songpo Y, Wen W et al (2009) Hepatitis C virus and lichen planus: a reciprocal association determined by a meta-analysis. Arch Dermatol 145:1040–1047PubMedGoogle Scholar
  91. 91.
    Maticic M (2007) Lichen planus in hepatitis C virus infection: an early marker that may save lives. Acta Dermatovenerol Alp Panonica Adriat 16:3–6Google Scholar
  92. 92.
    Carrozzo M (2008) Oral diseases associated with hepatitis C virus infection. Part 2: lichen planus and other diseases. Oral Dis 14:217–228PubMedGoogle Scholar
  93. 93.
    Grossmann SM, Teixeira R, de Aguiar MC et al (2008) Exacerbation of oral lichen planus lesions during treatment of chronic hepatitis C with pegylated interferon and ribavirin. Eur J Gastroenterol Hepatol 20:702–706Google Scholar
  94. 94.
    Sanchez MJ, Bergasa NV (2008) Hepatitis C associated cardiomyopathy: potential pathogenic mechanisms and clinical implications. Med Sci Monit 14:RA55–RA63PubMedGoogle Scholar
  95. 95.
    Matsumori A (2006) Role of hepatitis C virus in cardiomyopathies. Ernst Schering Res Found Workshop (55):99–120PubMedGoogle Scholar
  96. 96.
    Ohta K, Ueda T, Nagai S et al (1993) Pathogenesis of idiopathic pulmonary fibrosis — is hepatitis C virus involved? (in Japanese). Nihon Kyobu Shikkan Gakkai Zasshi 31Suppl:32–35PubMedGoogle Scholar
  97. 97.
    Kubo K, Yamaguchi S, Fujimoto K et al (1996) Bronchoalveolar lavage fluid findings in patients with chronic hepatitis C virus infection. Thorax 51:312–314PubMedPubMedCentralGoogle Scholar
  98. 98.
    Meliconi R, Andreone P, Fasano L et al (1996) Incidence of hepatitis C virus infection in Italian patients with idiopathic pulmonary fibrosis. Thorax 51:315–317PubMedPubMedCentralGoogle Scholar
  99. 99.
    Irving WL, Day S, Johnston ID (1993) Idiopathic pulmonary fibrosis and hepatitis C virus infection. Am Rev Respir Dis 148:1683–1684PubMedGoogle Scholar
  100. 100.
    Chen YC, Lu SN, Lin MC (2007) Interstitial pneumonitis after combination therapy with pegylated interferon alpha-2b and ribavirin for chronic hepatitis C. Chang Gung Med J 30:92–97PubMedGoogle Scholar
  101. 101.
    Arrieta JJ, Rodriguez-Inigo E, Ortiz-Movilla N et al (2001) In situ detection of hepatitis C virus RNA in salivary glands. Am J Pathol 158:259–264PubMedPubMedCentralGoogle Scholar
  102. 102.
    Ramos-Casals M, Loustaud-Ratti V, De Vita S et al (2005) Sjogren syndrome associated with hepatitis C virus: a multicenter analysis of 137 cases. Medicine (Baltimore) 84:81–89Google Scholar
  103. 103.
    Pillemer SR, Smith J, Fox PC et al (2005) Outcome measures for Sjogren’s syndrome, April 10-11, 2003, Bethesda, Maryland, USA. J Rheumatol 32:143–149PubMedGoogle Scholar
  104. 104.
    Haddad J, Deny P, Munz-Gotheil C et al (1992) Lymphocytic sialadenitis of Sjogren’s syndrome associated with chronic hepatitis C virus liver disease. Lancet 339:321–323PubMedGoogle Scholar
  105. 105.
    Carrozzo M (2008) Oral diseases associated with hepatitis C virus infection. Part 1. Sialadenitis and salivary glands lymphoma. Oral Dis 14:123–130PubMedGoogle Scholar
  106. 106.
    Rosner I, Rozenbaum M, Toubi E et al (2004) The case for hepatitis C arthritis. Semin Arthritis Rheum 33:375–387PubMedGoogle Scholar
  107. 107.
    Sene D, Ghillani-Dalbin P, Limal N et al (2006) Anti-cyclic citrullinated peptide antibodies in hepatitis C virus associated rheumatological manifestations and Sjogren’s syndrome. Ann Rheum Dis 65:394–397PubMedPubMedCentralGoogle Scholar
  108. 108.
    Wener MH, Hutchinson K, Morishima C et al (2004) Absence of antibodies to cyclic citrullinated peptide in sera of patients with hepatitis C virus infection and cryoglobulinemia. Arthritis Rheum 50:2305–2308PubMedGoogle Scholar
  109. 109.
    Denman AM (2000) Systemic lupus erythematosus — is a viral aetiology a credible hypothesis? J Infect 40:229–233Google Scholar
  110. 110.
    McMurray RW, Elbourne K (1997) Hepatitis C virus infection and autoimmunity. Semin Arthritis Rheum 26:689–701PubMedGoogle Scholar
  111. 111.
    Qin CL, Yang QY, Liao YX (2002) Analysis of clinical and immunological features of patients with systemic lupus erythematosus complicated by hepatitis C virus infection. Di Yi Jun Yi Da Xue Xue Bao 22:939–941PubMedGoogle Scholar
  112. 112.
    Wilson LE, Widman D, Dikman SH et al (2002) Autoimmune disease complicating antiviral therapy for hepatitis C virus infection. Semin Arthritis Rheum 32:163–173PubMedGoogle Scholar
  113. 113.
    Rajan SK, Espina BM, Liebman HA (2005) Hepatitis C virusrelated thrombocytopenia: clinical and laboratory characteristics compared with chronic immune thrombocytopenic purpura. Br J Haematol 129:818–824PubMedGoogle Scholar
  114. 114.
    Garcia-Suarez J, Burgaleta C, Hernanz N et al (2000) HCV-associated thrombocytopenia: clinical characteristics and platelet response after recombinant alpha2b-interferon therapy. Br J Haematol 110:98–103PubMedGoogle Scholar
  115. 115.
    Weksler BB (2007) Review article: the pathophysiology of thrombocytopenia in hepatitis C virus infection and chronic liver disease. Aliment Pharmacol Ther 26Suppl 1:13–19PubMedGoogle Scholar
  116. 116.
    Srinivasan R (2001) Autoimmune hemolytic anemia in treatment-naive chronic hepatitis C infection. J Clin Gastroenterol 32:245–247PubMedGoogle Scholar
  117. 117.
    Fernandez AB (2006) An unusual case of autoimmune hemolytic anemia in treatment naive hepatitis C virus infection. Hematology 11:385–387PubMedGoogle Scholar
  118. 118.
    Ramos-Casals M, Garcia-Carrasco M, Lopez-Medrano F et al (2003) Severe autoimmune cytopenias in treatment-naive hepatitis C virus infection: clinical description of 35 cases. Medicine (Baltimore) 82:87–96Google Scholar
  119. 119.
    Serna-Higuera C, Barcena-Marugan R, Sanz-de-Villalobos E (1999) Hemolytic anemia secondary to alpha-interferon treatment in a patient with chronic C hepatitis. J Clin Gastroenterol 28:358–359Google Scholar
  120. 120.
    Nomura H, Tanimoto H, Kajiwara E et al (2004) Factors contributing to ribavirin-induced anemia. J Gastroenterol Hepatol 19:1312–1317PubMedGoogle Scholar
  121. 121.
    Prieto J, Yuste JR, Beloqui O et al (1996) Anticardiolipin antibodies in chronic hepatitis C: implication of hepatitis C virus as the cause of the antiphospholipid syndrome. Hepatology 23:199–204PubMedGoogle Scholar
  122. 122.
    Leroy V, Arvieux J, Jacob MC et al (1998) Prevalence and significance of anticardiolipin, anti-beta2 glycoprotein I and anti-prothrombin antibodies in chronic hepatitis C. Br J Haematol 101:468–474PubMedGoogle Scholar
  123. 123.
    Harada M, Fujisawa Y, Sakisaka S et al (2000) High prevalence of anticardiolipin antibodies in hepatitis C virus infection: lack of effects on thrombocytopenia and thrombotic complications. J Gastroenterol 35:272–277PubMedGoogle Scholar
  124. 124.
    Ramos-Casals M, Cervera R, Lagrutta M et al (2004) Clinical features related to antiphospholipid syndrome in patients with chronic viral infections (hepatitis C virus/HIV infection): description of 82 cases. Clin Infect Dis 38:1009–1016PubMedGoogle Scholar
  125. 125.
    Cojocaru IM, Cojocaru M, Iacob SA (2005) High prevalence of anticardiolipin antibodies in patients with asymptomatic hepatitis C virus infection associated acute ischemic stroke. Rom J Intern Med 43:89–95PubMedGoogle Scholar
  126. 126.
    Mitchel LS, Jeffers LJ, Reddy KR et al (1993) Detection of hepatitis C virus antibody by first and second generation assays and polymerase chain reaction in patients with autoimmune chronic active hepatitis types I, II, and III. Am J Gastroenterol 88:1027–1034PubMedGoogle Scholar
  127. 127.
    Rust C, Beuers U (2008) Overlap syndromes among autoimmune liver diseases. World J Gastroenterol 14:3368–3373PubMedPubMedCentralGoogle Scholar
  128. 128.
    Strassburg CP, Manns MP (2009) Treatment of autoimmune hepatitis. Semin Liver Dis 29:273–285PubMedGoogle Scholar
  129. 129.
    Bellary S, Schiano T, Hartman G et al (1995) Chronic hepatitis with combined features of autoimmune chronic hepatitis and chronic hepatitis C: favorable response to prednisone and azathioprine. Ann Intern Med 123:32–34PubMedGoogle Scholar
  130. 130.
    Kee KM, Wang JH, Lee CM et al (2004) Chronic hepatitis C virus infection associated with dermatomyositis and hepatocellular carcinoma. Chang Gung Med J 27:834–839PubMedGoogle Scholar
  131. 131.
    Moazami G, Auran JD, Florakis GJ et al (1995) Interferon treatment of Mooren’s ulcers associated with hepatitis C. Am J Ophthalmol 119:365–366PubMedGoogle Scholar
  132. 132.
    Wang QS, Yuan J, Zhou SY et al (2008) Chronic hepatitis C virus infection is not associated with Mooren’s ulcer. Eye (Lond) 22:697–700Google Scholar
  133. 133.
    Schwartz KM, Skinner JA (2008) Hepatitis C-associated osteosclerosis: a case report. Skeletal Radiol 37:679–681PubMedGoogle Scholar
  134. 134.
    Ramos-Casals M, Mana J, Nardi N et al (2005) Sarcoidosis in patients with chronic hepatitis C virus infection: analysis of 68 cases. Medicine (Baltimore) 84:69–80Google Scholar
  135. 135.
    Hurst EA, Mauro T (2005) Sarcoidosis associated with pegylated interferon alfa and ribavirin treatment for chronic hepatitis C: a case report and review of the literature. Arch Dermatol 141:865–868PubMedGoogle Scholar

Copyright information

© Springer-Verlag 2010

Authors and Affiliations

  1. 1.Department of DermatologyInnsbruck Medical UniversityInnsbruckAustria

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