Hepatology International

, Volume 6, Issue 3, pp 606–612 | Cite as

Hepatitis C virus (genotype 4)-associated mixed cryoglobulinemia vasculitis: effects of antiviral treatment

  • Hisham R. El Khayat
  • Yasser M. Fouad
  • Ezzat Ali Ahmad
  • Hussein El Amin
  • Faten Ismael
  • Amal Rizk
Original Article



Type II mixed cryoglobulinemia (MC) is a systemic vasculitis usually associated with hepatitis C virus (HCV). The present trial was performed to investigate the efficacy of therapy with pegylated interferon alfa-2a (PEG-IFN alfa-2a) plus ribavirin in patients with HCV-related MC vasculitis and evaluate the factors associated with clinical remission of MC.


A total of 46 consecutive patients with HCV-related Type II MC received PEG-IFN alfa-2a (standard dose 180 mg/week) subcutaneously plus oral ribavirin (800–1,200 mg/day) for 48 weeks. The response to treatment was analyzed by comparing clinical, immunologic, and virologic parameters at the initial evaluation with those observed at the end of follow-up. Logistic regression was used to assess the factors associated with clinical remission.


A total of 22 patients (48%) had a sustained virologic response and were complete clinical responders. Serum cryoglobulin disappeared in 26 of 46 patients (56%), and complement levels normalized in 70% of the patients. In univariate analysis, factors associated with complete clinical response were early virologic response at 4 weeks [OR 1.4 (95% CI 0.1–17.1)], proteinuria [OR 1.4 (95% CI 0.2–8.2)] and the fibrosis score [OR 1.09 (95% CI 0.6–1.9)], peripheral neuropathy [OR 0.9 (95% CI 0.1–6.5)], arthralgia [OR 0.7 (95% CI 0.1–3.9)], sicca syndrome [OR 0.6 (95% CI 0.1–3.2)], cryoglobulin [OR 0.2 (95% CI 0.07–1.09)], and purpura [OR 0.1 (95% CI 0.01–1.3)]. In multivariate analysis, only cryoglobulinemia was independently associated with complete clinical response. No patient had side effects for which discontinuation of therapy was required.


The results indicated that treatment with PEG-IFN alfa-2a plus ribavirin can achieve a complete clinical response in patients with HCV-related MC. Complete clinical response correlates with the eradication of HCV.


Cryoglobulinemia Hepatitis C Interferon 


  1. 1.
    Cacoub P, Poynard T, Ghillani P, for the MULTIVIRC Group, et al. Extrahepatic manifestations of chronic hepatitis C. Arthritis Rheum 1999;42:2204–2212PubMedCrossRefGoogle Scholar
  2. 2.
    Agnello V, Chung RT, Kaplan LM. A role for hepatitis C virus infection in type II cryoglobulinemia. N Engl J Med 1992;327:1490–1495PubMedCrossRefGoogle Scholar
  3. 3.
    Misiani R, Bellavita P, Fenili D, et al. Interferon alfa-2a therapy in cryoglobulinemia associated with hepatitis C virus. N Engl J Med 1994;330:751–756PubMedCrossRefGoogle Scholar
  4. 4.
    Dammacco F, Sansonno D, Han JH, et al. Natural interferon versus its combination with 6-methyl-prednisolone in the therapy of type II mixed cryoglobulinemia: a long-term, randomized, controlled study. Blood 1994;84:3336–3343PubMedGoogle Scholar
  5. 5.
    Tarantino A, Campise M, Banfi G, et al. Long-term predictors of survival in essential mixed cryoglobulinemic glomerulonephritis. Kidney Int 1995;47:618–623PubMedCrossRefGoogle Scholar
  6. 6.
    Fried MW, Shiffman ML, Reddy KR, et al. Peginterferon alfa-2a plus ribavirin for chronic hepatitis C virus infection. N Engl J Med 2002;347:975–982PubMedCrossRefGoogle Scholar
  7. 7.
    Cacoub P, Saadoun D, Sene D, Limal N, Piette JC. Treatment of hepatitis C virus-related systemic vasculitis. J Rheumatol 2005;32:2078–2082PubMedGoogle Scholar
  8. 8.
    Saadoun D, Resche-Rigon M, Thibault V, Piette V, Cacoub P. Antiviral therapy for hepatitis C virus-associated mixed cryoglobulinemia vasculitis: a long-term followup study. Arthritis Rheum 2006;54(11):3696–3706PubMedCrossRefGoogle Scholar
  9. 9.
    The French METAVIR, Group CooperativeStudy, Bedossa P. Intraobserver and interobserver variations in liver biopsy interpretation in patients with chronic hepatitis C. Hepatology 1994;20:15–20Google Scholar
  10. 10.
    Musset L, Diemert MC, Taibi F, et al. Characterization of cryoglobulins by immunoblotting. Clin Chem 1992;38:798–802PubMedGoogle Scholar
  11. 11.
    Rustgi VK. The epidemiology of hepatitis C infection in the United States. J Gastroenterol 2007;42:513–521PubMedCrossRefGoogle Scholar
  12. 12.
    Mazzaro C, Zorat F, Caizzi M, et al. Treatment with peg-interferon α-2b and ribavirin of hepatitis C virus-associated mixed cryoglobulinemia: a pilot study. J Hepatol 2005;42:632–638PubMedCrossRefGoogle Scholar
  13. 13.
    Hauser SC, Pardi DS, Poterucha JJ. Mayo Clinic Gastroenterology and Hepatology Board Review. Mayo Clinic Scientific Press, MN (2006)Google Scholar
  14. 14.
    Liang TJ. Shortened therapy for hepatitis C virus genotype 2 or 3. Is less more? N Engl J Med 2007;357:176–178Google Scholar
  15. 15.
    Ali S, Meidinger RR, Kayali Z et al. Outcomes of pegylated interferon and ribavirin therapy for HCV patients with cryoglobulinemia as compared to patients without cryoglobulinemia. Gastroenterology 2007;132:A790Google Scholar
  16. 16.
    Cacoub P, Lidove O, Maisonobe T, et al. Interferon and ribavirin treatment in patients with hepatitis C virus-related systemic vasculitis. Arthritis Rheum 2002;46:3317–3326PubMedCrossRefGoogle Scholar
  17. 17.
    Naarendorp M, Kallemuchikkal U, Nuovo GJ, Gorevic PD. Long-term efficacy of interferon for extra hepatic disease associated with hepatitis C virus infection. J Rheumatol 2001;28:2466–2473PubMedGoogle Scholar
  18. 18.
    Zuckerman E, Keren D, Slobodin G, et al. Treatment of refractory, symptomatic, hepatitis C virus related mixed cryoglobulinemia with ribavirin and interferon. J Rheumatol 2000;27:2172–2178PubMedGoogle Scholar
  19. 19.
    Tallarita T, Gagliano M, Corona D, et al. (2009) Successful combination of Rituximab and plasma exchange in the treatment of cryoglobulinemic vasculitis with skin ulcers: a case report. Cases J 2:7859Google Scholar
  20. 20.
    Lamprecht P, Moosig F, Gause A, et al. Immunological and clinical follow up of hepatitis C virus associated cryoglobulinaemic vasculitis. Ann Rheum Dis 2001;60:385–390PubMedCrossRefGoogle Scholar
  21. 21.
    Alric L, Plaisier E, Thebault S, et al. Influence of antiviral therapy in hepatitis C virus-associated cryoglobulinemic MPGN. Am J Kidney Dis 2004;43:617–623PubMedCrossRefGoogle Scholar
  22. 22.
    Gota C, Fessler BJ, Calabrese LH, Cooper SM. Persistent cryoglobulinemic vasculitis following successful treatment of hepatitis C virus. J Rheumatol 2005;32:1164–1167PubMedGoogle Scholar
  23. 23.
    Roccatello D, Baldovino S, Rossi D, et al. Long-term effects of anti-CD20 monoclonal antibody treatment of cryoglobulinaemic glomerulonephritis. Nephrol Dial Transplant 2004;19:3054–3061PubMedCrossRefGoogle Scholar
  24. 24.
    Tallarita T, Gagliano M, Corona D, et al. Successful combination of Rituximab and plasma exchange in the treatment of cryoglobulinemic vasculitis with skin ulcers: a case report. Cases J 2009;2:7859Google Scholar
  25. 25.
    Manns MP, McHutchison JG, Gordon SC, et al. Peginterferon alfa-2b plus ribavirin compared with interferon alfa-2b plus ribavirin for initial treatment of Chronic hepatitis C: a randomized trial. Lancet 2001;358:958–965PubMedCrossRefGoogle Scholar
  26. 26.
    Dammacco F, Tucci FA, Lauletta G, et al. Pegylated interferon-alpha, ribavirin, and rituximab combined therapy of hepatitis C virus-related mixed cryoglobulinemia: A long-term study. Blood 2010;116(3):343–353Google Scholar

Copyright information

© Asian Pacific Association for the Study of the Liver 2011

Authors and Affiliations

  • Hisham R. El Khayat
    • 1
  • Yasser M. Fouad
    • 2
  • Ezzat Ali Ahmad
    • 3
  • Hussein El Amin
    • 4
  • Faten Ismael
    • 5
  • Amal Rizk
    • 6
  1. 1.Department of GastroenterologyTheodore Bilharz InstituteCairoEgypt
  2. 2.Department of Tropical MedicineMinia UniversityMiniaEgypt
  3. 3.Department of Internal MedicineAlexandria UniversityAlexandriaEgypt
  4. 4.Department of Internal MedicineAssiut UniversityAssiutEgypt
  5. 5.Department RheumatologyMinia UniversityMiniaEgypt
  6. 6.Department RheumatologyCairo UniversityCairoEgypt

Personalised recommendations