Skip to main content
Download PDF

Hepatitis C virus and autoimmunity

Autoimmunity Highlights volume 1, pages23–35(2010)Cite this 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.

References

  1. 1.

    Perrault M, Pecheur EI (2009) The hepatitis C virus and its hepatic environment: a toxic but finely tuned partnership. Biochem J 423:303–314

    PubMed  CAS  Google Scholar 

  2. 2.

    Lauer GM, Walker BD (2001) Hepatitis C virus infection. N Engl J Med 345:41–52

    PubMed  CAS  Google 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) 79:47–5

    CAS  Google 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 24:178–181

    PubMed  Google 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 24:507–515

    PubMed  Google 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 26:127–130

    PubMed  CAS  Google 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 95:745–752

    PubMed  CAS  Google Scholar 

  8. 8.

    Ferri C (2008) Mixed cryoglobulinemia. Orphanet J Rare Dis 3:25

    PubMed  PubMed Central  Google Scholar 

  9. 9.

    Benoist C, Mathis D (1998) Autoimmunity. The pathogen connection. Nature 394:227–228

    PubMed  CAS  Google 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 16:319–326

    PubMed  CAS  Google 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 133:404–413

    PubMed  CAS  PubMed Central  Google 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 31:339–344

    PubMed  CAS  PubMed Central  Google Scholar 

  13. 13.

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

    PubMed  CAS  Google 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 39:817–825

    PubMed  Google Scholar 

  15. 15.

    Ferri S, Muratori L, Lenzi M et al (2008) HCV and autoimmunity. Curr Pharm Des 14:1678–1685

    PubMed  CAS  Google 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 103:3428–3430

    PubMed  CAS  Google 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 8:18–23

    PubMed  CAS  Google Scholar 

  18. 18.

    Pileri P, Uematsu Y, Campagnoli S et al (1998) Binding of hepatitis C virus to CD81. Science 282:938–941

    PubMed  CAS  Google Scholar 

  19. 19.

    Pena LR, Nand S, De Maria N et al (2000) Hepatitis C virus infection and lymphoproliferative disorders. Dig Dis Sci 45:1854–1860

    PubMed  CAS  Google 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 27:134–139

    PubMed  CAS  Google Scholar 

  21. 21.

    Carter RH, Fearon DT (1992) CD19: lowering the threshold for antigen receptor stimulation of B lymphocytes. Science 256:105–107

    PubMed  CAS  Google 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 14:513–523

    PubMed  CAS  Google Scholar 

  23. 23.

    Agnello V, De Rosa FG (2004) Extrahepatic disease manifestations of HCV infection: some current issues. J Hepatol 40:341–352

    PubMed  Google Scholar 

  24. 24.

    Zignego AL, Brechot C (1999) Extrahepatic manifestations of HCV infection: facts and controversies. J Hepatol 31:369–376

    PubMed  CAS  Google Scholar 

  25. 25.

    Zignego AL, Giannelli F, Marrocchi ME et al (2000) T(14;18) translocation in chronic hepatitis C virus infection. Hepatology 31:474–479

    PubMed  CAS  Google 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 349:254–256

    PubMed  CAS  Google 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 25:833–837

    PubMed  CAS  Google 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 57:775–788

    Google 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 117:573–577

    PubMed  CAS  Google Scholar 

  30. 30.

    Saadoun D, Landau DA, Calabrese LH et al (2007) Hepatitis Cassociated mixed cryoglobulinaemia: a crossroad between autoimmunity and lymphoproliferation. Rheumatology (Oxford) 46:1234–1242

    CAS  Google 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 31:2199–2206

    PubMed  Google 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 19:841–848

    PubMed  CAS  Google 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 40:837–856

    PubMed  CAS  Google 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 21:305–312

    PubMed  CAS  Google Scholar 

  35. 35.

    Sansonno D, Carbone A, De Re V et al (2007) Hepatitis C virus infection, cryoglobulinaemia, and beyond. Rheumatology (Oxford) 46:572–578

    CAS  Google Scholar 

  36. 36.

    Ferri C, Mannini L, Bartoli V et al (1990) Blood viscosity and filtration abnormalities in mixed cryoglobulinemia patients. Clin Exp Rheumatol 8:271–281

    PubMed  CAS  Google 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 14:736–742

    PubMed  CAS  Google 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 54:316–323

    PubMed  CAS  Google 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–S134

    PubMed  Google Scholar 

  40. 40.

    Alpa M, Ferrero B, Cavallo R et al (2008) Anti-neuronal antibodies in patients with HCV-related mixed cryoglobulinemia. Autoimmun Rev 8:56–58

    PubMed  CAS  Google 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 31:382–385

    PubMed  Google Scholar 

  42. 42.

    Ferri C, Mascia MT (2006) Cryoglobulinemic vasculitis. Curr Opin Rheumatol 18:54–63

    PubMed  Google 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 60:808–812

    PubMed  Google 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 34:749–750

    PubMed  CAS  Google 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 23:403–406

    PubMed  CAS  Google 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 32:484–488

    PubMed  Google Scholar 

  47. 47.

    Tembl JI, Ferrer JM, Sevilla MT et al (1999) Neurologic complications associated with hepatitis C virus infection. Neurology 53:861–864

    PubMed  CAS  Google Scholar 

  48. 48.

    Kayali Z, Buckwold VE, Zimmerman B et al (2002) Hepatitis C, cryoglobulinemia, and cirrhosis: a meta-analysis. Hepatology 36:978–985

    PubMed  Google Scholar 

  49. 49.

    Ferri C, Bertozzi MA, Zignego AL (2002) Erectile dysfunction and hepatitis C virus infection. JAMA 288:698–699

    PubMed  Google 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 185:345–352

    PubMed  CAS  Google Scholar 

  51. 51.

    Witte L, Rupp J, Heyer P et al (2008) Fibrosing alveolitis with hepatitis C-related cryoglobulinemia (in German). Dtsch Med Wochenschr 133:709–712

    PubMed  CAS  Google 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 42:334–340

    PubMed  CAS  Google 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–S84

    PubMed  CAS  Google Scholar 

  54. 54.

    Ferri C, Zignego AL, Pileri SA (2002) Cryoglobulins. J Clin Pathol 55:4–13

    PubMed  CAS  PubMed Central  Google 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 33:791–792

    PubMed  CAS  Google 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 30:1775–1781

    PubMed  CAS  Google 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 27:2172–2178

    PubMed  CAS  Google 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 46:3317–3326

    PubMed  CAS  Google 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 43:1166–1167

    PubMed  Google 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 101:3818–3826

    PubMed  CAS  Google Scholar 

  61. 61.

    Zaja F, De Vita S, Mazzaro C et al (2003) Efficacy and safety of rituximab in type II mixed cryoglobulinemia. Blood 101:3827–3834

    PubMed  CAS  Google 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 29:543–547

    PubMed  CAS  Google Scholar 

  63. 63.

    Pozzato G, Mazzaro C, Crovatto M et al (1994) Low-grade malignant lymphoma, hepatitis C virus infection, and mixed cryoglobulinemia. Blood 84:3047–3053

    PubMed  CAS  Google 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 9:495–498

    PubMed  CAS  Google Scholar 

  65. 65.

    Mazzaro C, Tirelli U, Pozzato G (2005) Hepatitis C virus and non-Hodgkin’s lymphoma 10 years later. Dig Liver Dis 37:219–226

    PubMed  CAS  Google Scholar 

  66. 66.

    Weng WK, Levy S (2003) Hepatitis C virus (HCV) and lymphomagenesis. Leuk Lymphoma 44:1113–1120

    PubMed  CAS  Google 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 165:101–105

    PubMed  Google Scholar 

  68. 68.

    Zuckerman E, Zuckerman T (2002) Hepatitis C and B-cell lymphoma: the hemato-hepatologist linkage. Blood Rev 16:119–125

    PubMed  CAS  Google 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 90:776–782

    PubMed  Google 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 347:89–94

    PubMed  CAS  Google 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 23:468–473

    PubMed  CAS  Google 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 21:653–662

    PubMed  CAS  Google 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 20:4261–4267

    PubMed  CAS  Google 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 24:1563–1573

    PubMed  CAS  Google 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 36:1442–1448

    PubMed  Google 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 61:333–337

    PubMed  CAS  Google 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 11:257–262

    PubMed  CAS  Google Scholar 

  78. 78.

    Antonelli A, Ferri C, Pampana A et al (2004) Thyroid disorders in chronic hepatitis C. Am J Med 117:10–13

    PubMed  CAS  Google Scholar 

  79. 79.

    Prummel MF, Laurberg P (2003) Interferon-alpha and autoimmune thyroid disease. Thyroid 13:547–551

    PubMed  CAS  Google 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 32:209–217

    PubMed  CAS  Google 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 30:1059–1063

    PubMed  CAS  Google Scholar 

  82. 82.

    Serfaty L, Capeau J (2009) Hepatitis C, insulin resistance and diabetes: clinical and pathogenic data. Liver Int 29Suppl 2:13–25

    PubMed  CAS  Google 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 28:514–517

    PubMed  CAS  Google Scholar 

  84. 84.

    Lonardo A, Adinolfi LE, Petta S et al (2009) Hepatitis C and diabetes: the inevitable coincidence? Expert Rev Anti Infect Ther 7:293–308

    PubMed  Google 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 18:291–293

    PubMed  Google Scholar 

  86. 86.

    Doutre MS (1999) Hepatitis C virus-related skin diseases. Arch Dermatol 135:1401–1403

    PubMed  CAS  Google 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 39:620–627

    PubMed  Google Scholar 

  88. 88.

    Hadziyannis SJ (1998) Skin diseases associated with hepatitis C virus infection. J Eur Acad Dermatol Venereol 10:12–21

    PubMed  CAS  Google 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 5:142–151

    PubMed  CAS  Google 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 145:1040–1047

    PubMed  Google 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 16:3–6

    Google Scholar 

  92. 92.

    Carrozzo M (2008) Oral diseases associated with hepatitis C virus infection. Part 2: lichen planus and other diseases. Oral Dis 14:217–228

    PubMed  CAS  Google 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 20:702–706

    CAS  Google Scholar 

  94. 94.

    Sanchez MJ, Bergasa NV (2008) Hepatitis C associated cardiomyopathy: potential pathogenic mechanisms and clinical implications. Med Sci Monit 14:RA55–RA63

    PubMed  CAS  Google Scholar 

  95. 95.

    Matsumori A (2006) Role of hepatitis C virus in cardiomyopathies. Ernst Schering Res Found Workshop (55):99–120

    PubMed  Google 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:32–35

    PubMed  Google 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 51:312–314

    PubMed  CAS  PubMed Central  Google 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 51:315–317

    PubMed  CAS  PubMed Central  Google Scholar 

  99. 99.

    Irving WL, Day S, Johnston ID (1993) Idiopathic pulmonary fibrosis and hepatitis C virus infection. Am Rev Respir Dis 148:1683–1684

    PubMed  CAS  Google 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 30:92–97

    PubMed  CAS  Google 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 158:259–264

    PubMed  CAS  PubMed Central  Google 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) 84:81–89

    Google 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 32:143–149

    PubMed  Google 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 339:321–323

    PubMed  CAS  Google Scholar 

  105. 105.

    Carrozzo M (2008) Oral diseases associated with hepatitis C virus infection. Part 1. Sialadenitis and salivary glands lymphoma. Oral Dis 14:123–130

    PubMed  CAS  Google Scholar 

  106. 106.

    Rosner I, Rozenbaum M, Toubi E et al (2004) The case for hepatitis C arthritis. Semin Arthritis Rheum 33:375–387

    PubMed  Google 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 65:394–397

    PubMed  CAS  PubMed Central  Google 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 50:2305–2308

    PubMed  CAS  Google Scholar 

  109. 109.

    Denman AM (2000) Systemic lupus erythematosus — is a viral aetiology a credible hypothesis? J Infect 40:229–233

    Google Scholar 

  110. 110.

    McMurray RW, Elbourne K (1997) Hepatitis C virus infection and autoimmunity. Semin Arthritis Rheum 26:689–701

    PubMed  CAS  Google 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 22:939–941

    PubMed  Google 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 32:163–173

    PubMed  Google 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 129:818–824

    PubMed  Google 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 110:98–103

    PubMed  CAS  Google 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 1:13–19

    PubMed  CAS  Google Scholar 

  116. 116.

    Srinivasan R (2001) Autoimmune hemolytic anemia in treatment-naive chronic hepatitis C infection. J Clin Gastroenterol 32:245–247

    PubMed  CAS  Google Scholar 

  117. 117.

    Fernandez AB (2006) An unusual case of autoimmune hemolytic anemia in treatment naive hepatitis C virus infection. Hematology 11:385–387

    PubMed  CAS  Google 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) 82:87–96

    CAS  Google 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 28:358–359

    Google Scholar 

  120. 120.

    Nomura H, Tanimoto H, Kajiwara E et al (2004) Factors contributing to ribavirin-induced anemia. J Gastroenterol Hepatol 19:1312–1317

    PubMed  CAS  Google 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 23:199–204

    PubMed  CAS  Google 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 101:468–474

    PubMed  CAS  Google 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 35:272–277

    PubMed  CAS  Google 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 38:1009–1016

    PubMed  Google 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 43:89–95

    PubMed  Google 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 88:1027–1034

    PubMed  CAS  Google Scholar 

  127. 127.

    Rust C, Beuers U (2008) Overlap syndromes among autoimmune liver diseases. World J Gastroenterol 14:3368–3373

    PubMed  PubMed Central  Google Scholar 

  128. 128.

    Strassburg CP, Manns MP (2009) Treatment of autoimmune hepatitis. Semin Liver Dis 29:273–285

    PubMed  CAS  Google 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 123:32–34

    PubMed  CAS  Google 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 27:834–839

    PubMed  Google 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 119:365–366

    PubMed  CAS  Google 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) 22:697–700

    Google Scholar 

  133. 133.

    Schwartz KM, Skinner JA (2008) Hepatitis C-associated osteosclerosis: a case report. Skeletal Radiol 37:679–681

    PubMed  Google 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) 84:69–80

    CAS  Google 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 141:865–868

    PubMed  Google Scholar 

Download references

Author information

Affiliations

  1. Department of Dermatology, Innsbruck Medical University, Anichstrasse 35, A-6020, Innsbruck, Austria

    Barbara C. Böckle & Norbert T. Sepp

Authors
  1. Barbara C. Böckle
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Norbert T. Sepp
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Barbara C. Böckle.

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Böckle, B.C., Sepp, N.T. Hepatitis C virus and autoimmunity. Autoimmun Highlights 1, 23–35 (2010). https://doi.org/10.1007/s13317-010-0005-5

Download citation

Keywords

  • Hepatitis C
  • Extrahepatic manifestations
  • Autoimmune mechanism
  • Mixed cryoglobulinaemia vasculitis
  • Lymphoma

Autoimmunity Highlights

ISSN: 2038-3274

Contact us

\