For the integrated multidisciplinary approach to patient care

Return to the Southern Medical Journal

Current User S2 Access Level: -1 ()
CAN NOT ACCESS LEVEL 2
Review Article

Extrahepatic Manifestations of Hepatitis C

Nicole A. Palekar, MD, Stephen A. Harrison, MD
Volume: 98 Issue: 10 October, 2005

Abstract:

Hepatitis C affects approximately 170 million people worldwide. Extrahepatic manifestations of chronic hepatitis C infection are clinically evident in nearly 40% of patients. Much research has been done over the last decade to better understand their incidence, clinical presentation, mechanism of disease, and the role of antiviral therapy in their treatment. Of the commonly reported manifestations, cryoglobulinemia, membranoproliferative glomerulonephritis, and porphyria cutanea tarda remain the best understood manifestations. More recently, the association of insulin resistance and diabetes mellitus with chronic hepatitis C has been demonstrated. This paper serves to review the growing body of literature detailing the extrahepatic manifestations of chronic hepatitis C.


Key Points


* Extrahepatic manifestations are commonly seen in patients with hepatitis C.


* Mixed cryoglobulinemia, membranoproliferative glomerulonephritis and porphyria cutanea tarda appear to have the strongest association.


* Antiviral therapy with interferon 2a, interferon 2b, and ribaviron is effective in the treatment of some extrahepatic diseases but relapse rates are high if the virus is not eradicated.

Article:

This content is limited to qualifying members. Please click on an option below to view in full. Click here to compare all member plans.

Member Login

Silver/Gold members login for full access. Other members login to view purchase options.

Create a New Account

Create a new complimentary account/login to view purchase options.

Images:

This content is limited to qualifying members. Please click on an option below to view in full. Click here to compare all member plans.

Member Login

Silver/Gold members login for full access. Other members login to view purchase options.

Create a New Account

Create a new complimentary account/login to view purchase options.

References:

1. Lauer G, Walker B. Hepatitis C virus infection. N Engl J Med 2001;345:41–52.
2. Cacoub P, Renou C, Rosenthal E, et al. Extrahepatic manifestations associated with hepatitis C virus infection. Medicine 2000;79:47–56.
3. Cacoub P, Poynard T, Ghillani P, et al. Extrahepatic manifestations of hepatitis C virus. Arth Rheum1999;42:2204–2212.
4. Pawlotsky J, Roudot-Thoraval F, Simmonds P, et al. Extrahepatic immunologic manifestations in chronic hepatitis C and hepatitis C virus serotypes. Ann Intern Med 1995;122:169–173.
5. Pawlotsky J, Ben Yahia M, Andre C, et al. Immunological disorders in C virus chronic active hepatitis: a prospective study. Hepatology 1994;19:841–848.
6. Sikuler E, Shnaider A, Zilberman D, et al. Hepatitis C infection and extrahepatic malignancies. J Clin Gastroenterol 1997;24:87–89.
7. Pena L, Nand S, De Maria N, et al. Hepatitis C virus infection and lymphoproliferative disorders. Dig Dis and Sci 2000;45:1854–1860.
8. Meltzer M, Franklin EC. Cryoglobulinemia-a clinical and laboratory study. I. IgG and IgM cyroglobulins and factors affecting cryoprecipitability. Am J Med 1966;40:828.
9. Levey J, Bjornsson B, Banner B, et al. Mixed cryoglobulinemia in chronic hepatitis C infection.Medicine 1994;73:53–67.
10. Ferri C, Greco F, Longombardo G, et al. Antibodies against hepatitis C virus in mixed cryoglobulinemia patients. Infection 1991;19:417–420.
11. Ferri C, La Civita L, Zignego A, et al. Interferon-alpha in mixed cryoglobulinemia patients: randomized, crossover-controlled trial. Blood 1993;81:1132–1136.
12. Agnello V, Chung RT, Kaplan LM, et al. A role for hepatitis C virus infection in type II cryoglobulinemia. N Engl J Med 1992;327:1490–95.
13. Cacoub P, Lunel F, Musset L, et al. Hepatitis C virus and cryoglobulinemia. N Engl J Med1993;328:1121–4.
14. Akriviadis E, Xanthakis I, Navrozidou C, et al. Prevalence of cryoglobulinemia in chronic hepatitis C virus infection and response to treatment with interferon-alpha. J Clin Gastroenterol 1997;25:612–618.
15. Perniola R, De Rinaldis C, Accogli E, et al. Prevalence and clinical features of cryoglobulinaemia in multitransfused beta-thalassaemia patients. Ann Rheum Dis 1999;58:698–702.
16. Zignego A, Ferri C, Giannini C, et al. Hepatitis C virus genotype analysis in patients with type II mixed cryoglobulinemia. Ann Intern Med 1996;124:31–34.
17. Misiani R, Bellavita P, Fenili D, et al. Interferon alfa-2a therapy in cryoglobulinemia associated with hepatitis C virus. N Engl J Med 1994;330:751–756.
18. Akriviadis E, Xanthakis I, Navrozidou C, et al. Prevalence of cryoglobulinemia in chronic hepatitis C virus infection and response to treatment with interferon-[alpha]. J Clin Gastroenterol 1997;25:612–618.
19. Killenberg P. Extrahepatic manifestations of chronic hepatitis C. Sem Gastro Dis 2000;11:62–68.
20. Franzin F, Efremov D, Pozzato G. et al. Clonal B-cell expansions in peripheral blood of HCV-infected patients. Br J Haematol 1995;90:548–552.
21. Crouzier R, Martin T, Pasquali J. Monoclonal IgM rheumatoid factor secreted by CD5-negative B cells during mixed cryoglobulinemia. Evidence for somatic mutations and intraclonal diversity of the expressed VH region gene. J Immunol 1995;154:413–21.
22. Sarbah S, Younossi Z. Hepatitis C: an update on the silent epidemic. J Clin Gastroenterol2000;30:125–143.
23. Haddad J, Deny P, Munz-Gotheil C, et al. Lymphocytic sialadenitis of Sjogren’s syndrome associated with chronic hepatitis C virus liver disease. Lancet 1992;339:321–323.
24. Sthoeger Z, Fogel M, Ergas D, et al. Anticardiolipin antibodies in serum samples and cryoglobulins of patients with chronic hepatitis C infection. Ann Rheum Dis 2000;59:483–486.
25. Cacoub P, Ghillani P, Revelen R, et al. Anti-endothelial cell auto-antibodies in hepatitis C virus mixed cryoglobulinemia. J Hepatol 1999;31:598–603.
26. Rajan S, Liebman H. Treatment of hepatitis C related thrombocytopenia with interferon alpha. Amer J Hematol 2001;68:202–209.
27. Pivetti S, Novarino A, Merico F, et al. High prevalence of autoimmune phenomena in hepatitis C virus antibody positive patients with Lymphoproliferative and connective tissue disorders. Br J Haematol1996;95:204-211.
28. Kajihara M, Kato S, Okazaki Y, et al. A role of autoantibody-mediated platelet destruction in thrombocytopenia in patients with cirrhosis. Hepatology 2003;37:1267–1276.
29. Johnson R, Gretch D, Yamabe H, et al. Membranoproliferative glomerulonephritis associated with hepatitis C virus infection. N Engl J Med 1993;328:465–506.
30. Daghestani L, Pomeroy C. Renal manifestations of hepatitis C infection. Amer J Med 1999;106:347–352.
31. D’Amico G, Colasanti G, Ferrario F. Renal involvement in essential mixed cryoglobulinemia. Kidney Int 1989;35:1004–1014.
32. Bandi L. Renal manifestations of hepatitis C virus infection. Postgrad Med 2003;113:73–86.
33. Krane K, Gaglio P. Viral hepatitis as a cause of renal disease. South Med J 1999;92:354–360.
34. Marie-Sylvie D. Hepatitis C virus-related skin diseases. Arch Dermatol 1999;135:1401–1403.
35. English JC, Peake MF, Becker LE. Hepatitis C and porphyria cutanea tarda. Cutis 1996;57:404–408.
36. Dupin N, Chosidow O, Lunel F, et al. Essential mixed cryoglobulinemia: a comparative study of dermatologic manifestations in patients infected or noninfected with hepatitis C virus. Arch Dermatol1995;131:1124–1127.
37. Daoud M, Gibson L, Daoud S, et al. Chronic hepatitis C and skin diseases: a review. Mayo Clin Proc 1995;70:559–564.
38. Lodi G, Porter SR. Hepatitis C virus infection and lichen planus: a short review. Oral Dis 1997;3:77–81.
39. Schwaber M, Zlotogorski A. Dermatologic manifestations of hepatitis C infection. Int J Dermatol1997;36:251–254.
40. Zaltron S, Puoti M, Liberini P, et al. High prevalence of peripheral neuropathy in hepatitis C infected patients with symptomatic and asymptomatic cryoglobulinemia. Ital J Gastroenterol Hepatol1998;30:391–395.
41. Bonetti B, Scardoni M, Monaco S, et al. Hepatitis C virus infection of peripheral nerves in type II cryoglobulinaemia. Virchows Arch 1999;434:533–535.
42. Heckmann J, Kayser C, Heuss D, et al. Neurological manifestations of chronic hepatitis C. J Neurol1999;246:486–491.
43. Tembl J, Ferrer J, Sevilla M, et al. Neurologic complications associated with hepatitis C virus infection. Neurology 1999;53:861–864.
44. Lacaille F, Zylberberg H, Hagege H, et al. Hepatitis C associated with Guillain-Barre syndrome.Liver 1998;18:49–51.
45. Hui JM, Sud A, Farrell GC, et al. Insulin resistance is associated with chronic hepatitis C virus infection fibrosis progression. Gastroenterology 2003;125:1695–1704.
46. Lonardo A, Adinolfi LE, Loria P, et al. Steatosis and hepatitis C virus: mechanisms and significance for hepatic and extrahepatic disease. Gastroenterology 2004;122:1649–1657.
47. Shintani Y, Fujie H, Miyoshi H, et al. Hepatitis C virus infection and diabetes: direct involvement of the virus in the development of insulin resistance. Gastroenterology 2004;126:840–848.
48. Konrad T, Vicini P, Zeuzem S, et al. Interferon-alpha improves glucose intolerance in diabetic and non-diabetic patients with HCV-induced liver disease. Exp Clin Endo Diab 1999;107:343–349.
 

CME:

Portions of this issue may be available for CME credit. Please email education@sma.org for a complete listing of current Southern Medical Journal activities, as well as other SMA educational offerings.

This content is limited to qualifying members. Please click on an option below to view in full. Click here to compare all member plans.

Member Login

Silver/Gold members login for full access. Other members login to view purchase options.

Create a New Account

Create a new complimentary account/login to view purchase options.

This content is limited to qualifying members. Please click on an option below to view in full. Click here to compare all member plans.

Member Login

Silver/Gold members login for full access. Other members login to view purchase options.

Create a New Account

Create a new complimentary account/login to view purchase options.

Permissions