Background Essential mixed cryoglobulinemia is frequently associatedwith hepatitis C virus (HCV) infection. A beneficial effectof interferon alfa therapy has been reported, but we do notknow whether the antiviral activity of the drug affects theclinical and biochemical manifestations of disease.
Methods In a prospective randomized, controlled trial, we studied53 patients with HCV-associated type II cryoglobulinemia. Agroup of 27 patients received recombinant interferon alfa-2athrice weekly at a dose of 1.5 million units for a week andthen 3 million units thrice weekly for the following 23 weeks.The 26 control patients did not receive anything apart frompreviously prescribed treatments. All patients were then followedfor an additional 24 to 48 weeks.
Results Interferon was usually well tolerated, but it was permanentlydiscontinued in two patients because of atrial fibrillationand depression. Two of the 26 patients in the control groupwere lost to follow-up. After the treatment period, serum HCVRNA was undetectable in 15 of the remaining 25 patients whoreceived interferon alfa-2a, but in none of the controls. Incomparison with the control group, the 15 patients with undetectablelevels of HCV RNA in serum had significant improvement in cutaneousvasculitis (P = 0.04) and significant decreases in serum levelsof anti-HCV-antibody activity (P = 0.007), cryoglobulins (P= 0.002), IgM (P = 0.002), rheumatoid factor (P = 0.001), andcreatinine (P = 0.006). After treatment with interferon alfa-2awas discontinued, viremia and cryoglobulinemia recurred in all15 HCV RNA-negative patients. On resumption of treatment, threeof four patients had a virologic, clinical, and biochemicalresponse.
Conclusions The therapeutic efficacy of interferon alfa-2a inHCV-associated cryoglobulinemia is closely related to its antiviralactivity, thus supporting the idea that HCV infection may bea cause of this disease.
Source Information
From the Division of Nephrology and Dialysis (R.M., D.M.), the Department of Immunohematology and the Blood Transfusion Center (P.B., O.V.), the Laboratory of Clinical Chemistry (P.Z., A.V.), and the Division of Medicine I (P.L.S.), Ospedali Riuniti di Bergamo, Bergamo; the Laboratory of Clinical Chemistry (D.F.) and the Dialysis Unit (M.M., G.V.), Ospedale di Treviglio e Caravaggio, Treviglio; and the Institute of Virology, University of Milan, School of Medicine, Milan (E.T., A.Z.) -- all in Italy.
Address reprint requests to Dr. Bellavita at the Department of Immunohematology and the Blood Transfusion Center, Ospedali Riuniti di Bergamo, 24128 Bergamo, Italy.
Cacoub, P, Delluc, A, Saadoun, D, Landau, D A, Sene, D
(2008). Anti-CD20 monoclonal antibody (rituximab) treatment for cryoglobulinemic vasculitis: where do we stand?. Ann Rheum Dis
67: 283-287
[Abstract][Full Text]
Viswanatha, D S, Dogan, A
(2007). Hepatitis C virus and lymphoma. J. Clin. Pathol.
60: 1378-1383
[Abstract][Full Text]
Saadoun, D., Landau, D. A., Calabrese, L. H., Cacoub, P. P.
(2007). Hepatitis C-associated mixed cryoglobulinaemia: a crossroad between autoimmunity and lymphoproliferation. Rheumatology (Oxford)
46: 1234-1242
[Abstract][Full Text]
Terrault, N. A., Adey, D. B.
(2007). The Kidney Transplant Recipient with Hepatitis C Infection: Pre- and Posttransplantation Treatment. CJASN
2: 563-575
[Abstract][Full Text]
Prasad, M., Buller, G. K., Mena, C. I., Sofair, A. N.
(2006). Sum of the Parts. NEJM
355: 2468-2473
[Full Text]
Kay, J., McCluskey, R. T.
(2005). Case records of the Massachusetts General Hospital. Case 31-2005. A 60-year-old man with skin lesions and renal insufficiency.. NEJM
353: 1605-1613
[Full Text]
Roccatello, D., Baldovino, S., Rossi, D., Mansouri, M., Naretto, C., Gennaro, M., Cavallo, R., Alpa, M., Costanzo, P., Giachino, O., Mazzucco, G., Sena, L. M.
(2004). Long-term effects of anti-CD20 monoclonal antibody treatment of cryoglobulinaemic glomerulonephritis. Nephrol Dial Transplant
19: 3054-3061
[Abstract][Full Text]
Aljurf, M. D., Owaidah, T. W., Ezzat, A., Ibrahim, E., Tbakhi, A.
(2003). Antigen- and/or immune-driven lymphoproliferative disorders. Ann Oncol
14: 1595-1606
[Full Text]
Bruchfeld, A., Lindahl, K., Stahle, L., Soderberg, M., Schvarcz, R.
(2003). Interferon and ribavirin treatment in patients with hepatitis C-associated renal disease and renal insufficiency. Nephrol Dial Transplant
18: 1573-1580
[Abstract][Full Text]
Bruchfeld, A., Lindahl, K., Stahle, L., Soderberg, M., Schvarcz, R.
(2003). Interferon and ribavirin treatment in patients with hepatitis C-associated renal disease and renal insufficiency. Nephrol Dial Transplant
18: 1573-1580
[Abstract][Full Text]
Ramos-Casals, M., Trejo, O., Garcia-Carrasco, M., Font, J.
(2003). Therapeutic management of extrahepatic manifestations in patients with chronic hepatitis C virus infection. Rheumatology (Oxford)
42: 818-828
[Full Text]
Sansonno, D., De Re, V., Lauletta, G., Tucci, F. A., Boiocchi, M., Dammacco, F.
(2003). Monoclonal antibody treatment of mixed cryoglobulinemia resistant to interferon alpha with an anti-CD20. Blood
101: 3818-3826
[Abstract][Full Text]
Zaja, F., De Vita, S., Mazzaro, C., Sacco, S., Damiani, D., De Marchi, G., Michelutti, A., Baccarani, M., Fanin, R., Ferraccioli, G.
(2003). Efficacy and safety of rituximab in type II mixed cryoglobulinemia. Blood
101: 3827-3834
[Abstract][Full Text]
Sabry, A. A., Sobh, M. A., Sheaashaa, H. A., Kudesia, G., Wild, G., Fox, S., Wagner, B. E., Irving, W. L., Grabowska, A., El-Nahas, A. M.
(2002). Effect of combination therapy (ribavirin and interferon) in HCV-related glomerulopathy. Nephrol Dial Transplant
17: 1924-1930
[Abstract][Full Text]
Rieu, V., Cohen, P., Andre, M.-H., Mouthon, L., Godmer, P., Jarrousse, B., Lhote, F., Ferriere, F., Deny, P., Buchet, P., Guillevin, L.
(2002). Characteristics and outcome of 49 patients with symptomatic cryoglobulinaemia. Rheumatology (Oxford)
41: 290-300
[Abstract][Full Text]
Ferri, C, Zignego, A L, Pileri, S A
(2002). Cryoglobulins. J. Clin. Pathol.
55: 4-13
[Abstract][Full Text]
Jayne, D.
(2000). Evidence-based treatment of systemic vasculitis. Rheumatology (Oxford)
39: 585-595
[Full Text]
Ramos-Casals, M., Trejo, O., Garcia-Carrasco, M., Cervera, R., Font, J.
(2000). Mixed cryoglobulinemia: new concepts. Lupus
9: 83-91
[Abstract]
Fernandez-Gutierrez, B., Zamorano, J., Batlle, E., Alfonso, F., Conde, A., Sanchez-Harguindey, L., Jover, J. A.
(1999). Coronary dissection associated with hepatitis C virus-related cryoglobulinaemia. Rheumatology (Oxford)
38: 1299-1301
[Full Text]
Hohler, T., Kriegsmann, J., Laukhuf, F., Meyer zum Buschenfelde, K.-H., Wandel, E.
(1999). The lady with a history of blood transfusion who developed palpable purpura and microhaematuria. Nephrol Dial Transplant
14: 2035-2037
[Full Text]
CROSBIE, O M, ALEXANDER, G J M
(1999). Cryoglobulinaemia in HCV infection: coming in from the cold. Gut
45: 8-9
[Full Text]
Cresta, P, Musset, L, Cacoub, P, Frangeul, L, Vitour, D, Poynard, T, Opolon, P, Nguyen, D-T, Golliot, F, Piette, J-C, Huraux, J-M, Lunel, F
(1999). Response to interferon alpha treatment and disappearance of cryoglobulinaemia in patients infected by hepatitis C virus. Gut
45: 122-128
[Abstract][Full Text]
Wang, H., Eckels, D. D.
(1999). Mutations in Immunodominant T Cell Epitopes Derived from the Nonstructural 3 Protein of Hepatitis C Virus Have the Potential for Generating Escape Variants That May Have Important Consequences for T Cell Recognition. J. Immunol.
162: 4177-4183
[Abstract][Full Text]
Casato, M., Lagana, B., Pucillo, L. P., Quinti, I.
(1998). Interferon for Hepatitis C Virus-Negative Type II Mixed Cryoglobulinemia. NEJM
338: 1386-1387
[Full Text]
Ferri, C, La Civita, L, Longombardo, G, Zignego, A L, Pasero, G
(1998). Mixed cryoglobulinaemia: a cross-road between autoimmune and lymphoproliferative disorders. Lupus
7: 275-279
[Abstract]
Casato, M., Agnello, V., Pucillo, L. P., Knight, G. B., Leoni, M., Del Vecchio, S., Mazzilli, C., Antonelli, G., Bonomo, L.
(1997). Predictors of Long-Term Response to High-Dose Interferon Therapy in Type II Cryoglobulinemia Associated With Hepatitis C Virus Infection. Blood
90: 3865-3873
[Abstract][Full Text]
De Vita, S., Sacco, C., Sansonno, D., Gloghini, A., Dammacco, F., Crovatto, M., Santini, G., Dolcetti, R., Boiocchi, M., Carbone, A., Zagonel, V.
(1997). Characterization of Overt B-Cell Lymphomas in Patients With Hepatitis C Virus Infection. Blood
90: 776-782
[Abstract][Full Text]
Mariette, X., Chastang, C., Louboutin, J.-P., Leger, J.-M., Clavelou, P., Brouet, J.-C.
(1997). A randomised clinical trial comparing interferon-alpha and intravenous immunoglobulin in polyneuropathy associated with monoclonal IgM. J. Neurol. Neurosurg. Psychiatry
63: 28-34
[Abstract][Full Text]
García-Carrasco, M., Ramos, M., Cervera, R., Font, J., Vidal, J., Muñoz, F. J, Miret, C., Espinosa, G., Ingelmo, M.
(1997). Hepatitis C virus infection in `primary' Sjogren's syndrome: prevalence and clinical significance in a series of 90 patients. Ann Rheum Dis
56: 173-175
[Abstract][Full Text]
Hoofnagle, J. H., Di Bisceglie, A. M.
(1997). The Treatment of Chronic Viral Hepatitis. NEJM
336: 347-356
[Full Text]
Munke, H., Stockmann, F., Ramadori, G.
(1995). Possible Association between Behcet's Syndrome and Chronic Hepatitis C Virus Infection. NEJM
332: 400-401
[Full Text]
Simon, H. J., Gurakan, B., Oran, O., Yigit, S., Tighe, M. K., Miskovitz, P., Leon, J., Ohto, H., Okamoto, H., Mishiro, S.
(1994). Vertical Transmission of Hepatitis C Virus. NEJM
331: 399-400
[Full Text]
Agnello, V., Knight, G., Abel, G., Ganger, D. R., Jensen, D. M., Misiani, R., Bellavita, P., Vicari, O.
(1994). Interferon Alfa-2a for Cryoglobulinemia Associated with Hepatitis C Virus. NEJM
331: 400-401
[Full Text]