Skip to main content

Advertisement

Log in

Hepatitis C virus outside the liver

  • Published:
Current Hepatitis Reports Aims and scope Submit manuscript

Abstract

Observational and some experimental data suggest that hepatitis C virus can manifest in a variety of disease processes outside the liver. The links between hepatitis C virus and membranoproliferative glomerulonephropathy, porphyria cutanea tarda, lichen planus, cryoglobulinemia, diabetes mellitus, B-cell non-Hodgkin’s lymphoma, and thyroiditis are critically reviewed. Based on the available evidence, recommendations for the clinical approach to patients with extrahepatic diseases are discussed.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References and Recommended Reading

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

    Article  PubMed  CAS  Google Scholar 

  2. Cacoub P, Renou C, Rosenthal E: Extrahepatic manifestations associated with hepatitis C virus infection: a prospective multicenter study of 321 patients. Medicine 2000, 79:47–56. Reports on a survey of symptom and laboratory evidence of extrahepatic manifestations in a large cohort of HCV patients. It is most notable because of the comprehensive look at multiple disorders in one survey.

    Article  PubMed  CAS  Google Scholar 

  3. DeCastro M, Sanchez J, Herrera JF, et al.: Hepatitis C virus antibodies and liver disease in patients with porphyria cutanea tarda. Hepatology 1993, 17:551–557.

    Article  PubMed  CAS  Google Scholar 

  4. El-Serag HB, Hampel H, Yeh C, Rabeneck L: Extrahepatic manifestations of hepatitis C among United States male veterans. Hepatology 2002, 36:1439–1445. These authors performed the largest case-control study in this field, using the clinical database of the VA Medical Centers to examine patterns of diagnostic coding as evidence of association between HCV and other disorders. Although the method is indirect, there are notable positive and negative data generated in this unique study.

    PubMed  Google Scholar 

  5. Cacoub P, Ratziu V, Myers RP, et al.: Impact of treatment on extra hepatic manifestations in patients with chronic hepatitis C. J Hepatol 2002, 36:812–818.

    Article  PubMed  Google Scholar 

  6. Cacoub P, Poynard T, Ghillani P: Extrahepatic manifestations of chronic hepatitis C. Arthritis Rheum 1999, 42:2204–2212.

    Article  PubMed  CAS  Google Scholar 

  7. Herrero C, Vicente A, Bruguera M, et al.: Is hepatitis C virus infection a trigger of porphyria cutanea tarda? Lancet 1993, 341:788–789.

    Article  PubMed  CAS  Google Scholar 

  8. Mignogna MD, Muzio LL, Favia G: Oral lichen planus and HCV infection: a clinical evaluation of 263 cases. Int J Dermatol 1998, 37:575–578.

    Article  PubMed  CAS  Google Scholar 

  9. Cribier B, Garnier C, Laustriat D, Heid E: Lichen planus and hepatitis C virus infection: an epidemiologic study. J Am Acad Dermatol 1994, 31:1070–1072.

    PubMed  CAS  Google Scholar 

  10. Pawlotsky JM, Ben Hayia M, Andre C, et al.: Immunological disorders in C virus chronic active hepatitis: a prospective case-control study. Hepatology 1994, 19:841–848.

    Article  PubMed  CAS  Google Scholar 

  11. Carson CW, Conn DL, Czaja AJ, et al.: Frequency and significance of antibodies to hepatitis C virus in polyarteritis nodosa. J Rheumatol 1993, 20:304–309.

    PubMed  CAS  Google Scholar 

  12. Cacoub P, Lunel-Fabiani F, Du LT, et al.: Polyarteritis nodosa and hepatitis C virus infection. Ann Intern Med 1992, 116:605–606.

    PubMed  CAS  Google Scholar 

  13. Marazuela M, Garcia-Buery L, Gonzalez-Fernandez B, et al.: Thyroid autoimmune disorders in patients with chronic hepatitis C before and during interferon-alpha therapy. Clin Endocrinol 1996, 44:635–642.

    Article  CAS  Google Scholar 

  14. Mason AL, Lau JY, Hoang N: Association of diabetes mellitus and chronic hepatitis C virus infection. Hepatology 1999, 29:328–333.

    Article  PubMed  CAS  Google Scholar 

  15. Misiani R, Bellavita P, Fenili D, Borelli G: Hepatitis c virus infection in patients with essential mixed cryoglobulinemia. Ann Intern Med 1992, 117:573–577.

    PubMed  CAS  Google Scholar 

  16. Yamabe H, Johnson R, Gretch DR, et al.: Hepatitis C virus infection and membranoproliferative glomerulonephritis in Japan. J Am Soc Nephrol 1995, 6:220–223.

    PubMed  CAS  Google Scholar 

  17. Ferri C, Francesco C, Zignego AL: Hepatitis C virus infection in patients with non-Hodgkin’s lymphoma. Br J Haematol 1994, 88:392–394.

    PubMed  CAS  Google Scholar 

  18. Ferri C, Baicchi U, la Civita L, et al.: Hepatitis C virus-related autoimmunity in patients with porphyria cutanea tarda. Eur J Clin Invest 1993, 23:851–855.

    PubMed  CAS  Google Scholar 

  19. Clifford BD, Donahue D, Smith L, et al.: High prevalence of serological markers of autoimmunity in patients with chronic hepatitis C. Hepatology 1995, 21:613–619.

    PubMed  CAS  Google Scholar 

  20. Custro N, Montalto G, Scafidi V, et al.: Prospective study on thyroid autoimmunity and dysfunction related to chronic hepatitis C and interferon therapy. J Endocrinol Invest 1997, 20:374–380.

    PubMed  CAS  Google Scholar 

  21. Deutsch M, Dourakis S, Manesis EK, Gioustozi A: Thyroid abnormalities in chronic viral hepatitis and their relationship to interferon alfa therapy. Hepatology 1997, 26:206–210.

    Article  PubMed  CAS  Google Scholar 

  22. Boadas J, Rodriguez-Espinosa J, Enrequez J, et al.: Prevalence of thyroid autoantibodies is not increased in blood donors with hepatitis C virus infection. J Hepatol 1995, 22:611–615.

    Article  PubMed  CAS  Google Scholar 

  23. Prieto J, Yuste JR, Beloqui O, et al.: Anticardiolipin antibodies in chronic hepatitis C: implication of hepatitis C virus as the cause of the antiphospholipid syndrome. Hepatology 1996, 23:199–204.

    Article  PubMed  CAS  Google Scholar 

  24. Pawlotsky JM, Roudot-Thoraval F, Simmonds P: Extrahepatic immunologic manifestations in chronic hepatitis C and hepatitis C virus serotypes. Ann Intern Med 1995, 122:169–173.

    PubMed  CAS  Google Scholar 

  25. Johnson RJ, Gretch DR, Hideaki Y, et al.: Membranoproliferative glomerulonephritis associated with hepatitis C virus infection. N Engl J Med 1993, 328:465–470.

    Article  PubMed  CAS  Google Scholar 

  26. Jefferson JA, Johnson RJ: Treatment of hepatitis C-associated glomerular disease. Semin Nephrol 2000, 20:286–292.

    PubMed  CAS  Google Scholar 

  27. Perez-Calvo J, Lasierra P, Moros M, Inigo P: Role of ribavirin in membranoproliferative glomerulonephritis associated with hepatitis C virus infection refractory to alpha-interferon. Nephron 2002, 92:459–462.

    Article  PubMed  Google Scholar 

  28. Lacour JP, Bodokh I, Castanet J, et al.: Porphyria cutanea tarda and antibodies to hepatitis C virus. Br J Dermatol 1993, 128:121–123.

    Article  PubMed  CAS  Google Scholar 

  29. Fargion S, Piperno A, Cappellini MD, et al.: Hepatitis C virus and porphyria cutanea tarda; evidence of a strong association. Hepatology 1992, 16:1322–1326.

    Article  PubMed  CAS  Google Scholar 

  30. Chuang TY, Stitle L, Brashaer R, Lewis C: Hepatitis C virus and lichen planus: a case-control study of 340 patients. J Am Acad Dermatol 1999, 41:787–789.

    Article  PubMed  CAS  Google Scholar 

  31. Kerr GS, Rofail M, Lewis JH, et al.: Prevalence of hepatitis C virus associated cryoglobulinemia at a Veterans Hospital. J Rheumatol 1996, 24:2134–2138.

    Google Scholar 

  32. Lunel F, Musset L, Cacoub P, et al.: Cryoglobulinemia in chronic liver diseases: role of hepatitis C virus and liver damage. Gastroenterology 1994, 106:1291–1300.

    PubMed  CAS  Google Scholar 

  33. Ferri C, Greco F, Longombardo G, et al.: Hepatitis C virus antibodies in mixed cryoglobulinemia. Clin Exp Rheumatol 1991, 9:95–96.

    PubMed  CAS  Google Scholar 

  34. Misiani R, Bellavita P, Fenili D: Interferon alpha-2a therapy in cryoglobulinemia associated with hepatitis C virus. N Engl J Med 1994, 330:751–756.

    Article  PubMed  CAS  Google Scholar 

  35. Naarendorp M, Kallemuchikkal U, Nuovo G: Long-term efficacy of interferon-alpha for extrahepatic disease associated with hepatitis c virus infection. J Rheumatol 2001, 28:2466–2473.

    PubMed  CAS  Google Scholar 

  36. Silvestri F, Sperotto A, Fanin R: Hepatitis C and lymphoma. Curr Hepatitis Rep 2002, 1:5–8.

    Article  Google Scholar 

  37. Ferri C, Monti M, Civita L, et al.: Hepatitis C virus infection in non-hodgkin’s b-cell lymphoma complicating mixed cryoglobulinaemia. Eur J Clin Invest 1994, 24:781–784.

    Article  PubMed  CAS  Google Scholar 

  38. Mazzaro C, Zagonel V, Monfardini S, Tulissi P: Hepatitis C virus and non-hodgkin’s lymphomas. Br J Haematol 1996, 94:544–550.

    Article  PubMed  CAS  Google Scholar 

  39. Silvestri F, Pipan C, Barillari G, et al.: Prevalence of hepatitis C virus infection in patients with lymphoproliferative disorders. Blood 1996, 87:4296–4301.

    PubMed  CAS  Google Scholar 

  40. Silvestri F, Baccarani M: Hepatitis C virus-related lymphoma. Br J Haematol 1997, 99:475–480.

    Article  PubMed  CAS  Google Scholar 

  41. Collier J, Zanke B, Moore M, et al.: No association between hepatitis C and B-cell lymphoma. Hepatology 1999, 29:1259–1261.

    Article  PubMed  CAS  Google Scholar 

  42. Zuckerman E, Zuckerman T, Levine AM, et al.: Hepatitis C virus infection in patients with B-cell non-Hodgkin lymphoma. Ann Intern Med 1997, 127:423–428.

    PubMed  CAS  Google Scholar 

  43. Pioltelli P, Gargantini L, Cassi E, et al.: Hepatitis C virus in non-hodgkin’s lymphoma. A reappraisal after a prospective case-control study of 300 patients. Am J Hematol 2000, 64:95–100.

    Article  PubMed  CAS  Google Scholar 

  44. Lerat H, Rumm S, Hubersetzer F, et al.: In vivo tropism of hepatitis C virus genomic sequences in hematopoietic cells: influence of viral load, viral genotype and cell phenotype. Blood 1998, 91:3841–3849.

    PubMed  CAS  Google Scholar 

  45. Andreone P, Zignego AL, Cursaro C, et al.: Prevalence of monoclonal gammopathies in patients with hepatitis C virus infection. Ann Intern Med 1998, 129:294–298.

    PubMed  CAS  Google Scholar 

  46. Patriarca F, Silvestri F, Fanin R, et al.: Long-lasting complete remission of hepatitis C virus (HCV) infection and HCVassociated immunocytoma with alpha-interferon treatment. Br J Haematol 2001, 112:370–372.

    Article  PubMed  CAS  Google Scholar 

  47. Sperotto A, Silvestri F, Fanin R, et al.: Autologous stem cell transplantation in chronic carriers of hepatitis B virus and hepatitis C virus affected by onco-haematological diseases. Haematologica 1999, 84:1052–1053.

    Google Scholar 

  48. Huang MJ, Tsai SL, Huang BY, et al.: Prevalence and significance of thyroid autoantibodies in patients with chronic hepatitis C virus infection: a prospective controlled study. Clin Endocrinol 1999, 50:503–509.

    Article  CAS  Google Scholar 

  49. Ganne-Carrie N, Medini A, Coderc E, et al.: Latent autoimmune thyroiditis in untreated patients with HCV chronic hepatitis: a case-control study. J Autoimmunity 2000, 14:189–193.

    Article  CAS  Google Scholar 

  50. Fernandez-Soto L, Gonzalez A, Escobar-Jimenez F, Vazquez R: Increased risk of autoimmune thyroid disease in hepatitis C vs hepatitis B before, during, and after discontinuing interferon therapy. Arch Intern Med 1998, 158:1445–1448.

    Article  PubMed  CAS  Google Scholar 

  51. Ozyilkan E, Arslan M: Increased prevalence of diabetes mellitus in patients with chronic hepatitis C virus infection [letter]. Am J Gastroenterol 1996, 91:1480–1481.

    PubMed  CAS  Google Scholar 

  52. Caronia S, Taylor K, Pagliaro L: Further evidence for an association between non-insulin-dependent diabetes mellitus and chronic hepatitis C virus infection. Hepatology 1999, 30:1059–1063.

    Article  PubMed  CAS  Google Scholar 

  53. Gray H, Wreghitt T, Stratton IM, et al.: High prevalence of hepatitis C infection in Afro-Caribbean patients with type 2 diabetes and abnormal liver function tests. Diabet Med 1995, 12:244–249.

    Article  PubMed  CAS  Google Scholar 

  54. Simo R, Hernandez C, Genesca J: High prevalence of hepatitis C virus infection in diabetic patients. Diabetes Care 1996, 19:998–1000.

    Article  PubMed  CAS  Google Scholar 

  55. Mehta SH, Brancati FL, Sulkowski MS, Strathdee S: Prevalence of type 2 diabetes mellitus among persons with hepatitis C virus infection in the United States. Ann Intern Med 2000, 133:592–599. These authors looked at the association between diabetes mellitus and HCV by using the NHANES III survey data. Thus far, this is the only study to use systematic screening in a sample and avoid selection bias.

    PubMed  CAS  Google Scholar 

  56. Mangia A, Schiavone G, Lezzi G: HCV and diabetes mellitus: evidence for a negative association. Am J Gastroenterol 1998, 93:2363–2367.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Fox, R.K. Hepatitis C virus outside the liver. Curr hepatitis rep 2, 116–124 (2003). https://doi.org/10.1007/s11901-003-0005-2

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11901-003-0005-2

Keywords

Navigation