Abstract
Mixed cryoglobulinemia is a systemic disease, almost always associated with hepatitis C virus infection and characterized by purpura and cutaneous vasculitis, asthenia, arthralgias, and often renal and neurological involvement. No significant differences have been described to date in mixed cryoglobulinemia patients with type 1, 2, or 3 hepatitis C virus infection with respect to symptoms, while a higher prevalence of genotype 2a has been reported in patients without clinical and biochemical signs of liver disease or with serum autoantibodies. We examined 33 hepatitis C virus-positive patients with mixed cryoglobulinemia to assess if any clinical or serological feature is related to infection with different genotypes. All subjects underwent viral genotype determination by means of a single-step polymerase chain reaction. Thirteen patients (39%) were infected with hepatitis C virus type 1b, 17 (52%) with type 2a or 2a/c, and 3 (9%) with type 3. There was a significant difference in the frequency of peripheral nervous system involvement: paresthesias or other symptoms of peripheral neuropathy were less frequent in patients with 2a or 2a/c infection (29%) than in patients with type 1b or type 3 infection (88%,P=0.003). Only patients with hepatitis C virus type 2 had urticaria or cutaneous ulcers. These patients also had a lower frequency of arthralgias, lower cryocrit values (P=0.02), and lower serum levels of alanine-aminotransferase and γ-glutamyl-transpeptidase (P<0.04) than patients with type 1 and type 3 infection. The prevalence of antinuclear antibody positivity was similar in the three groups.
Similar content being viewed by others
References
Meltzer M, Franklin EC, Elias K, McCluskey RT, Cooper N. Cryoglobulinemia. A clinical and laboratory study. II. Cryoglobulins with rheumatoid factor activity. Am J Med 1966; 40:837.
Ferri C, Greco F, Longombardo G, Palla P, Moretti A, Marzo E, Mazzoni A, Pasero G. Bombardieri S. Association between hepatitis C virus and mixed cryoglobulinemia. Clin Exp Rheumatol 1991; 9:621.
Ferri C, Marzo E, Longombardo G, Lombardini F, LaCivita L, Vanacore R, Liberati AM, Gerli R, Greco F, Moretti A, Monti N, Gentilini P, Bombardieri S, Zignego AL. Interferon-alpha in mixed cryoglobulinemia patients: randomized, crossover-controlled trial. Blood 1993; 81:1132.
Agnello V, Chung RT, Kaplan RM. A role for hepatitis C virus infection in type II cryoglobulinemia. N Engl J Med 1992; 327:1490.
Lunel F, Musset L, Cacoub P, Frangeul L, Cresta P, Perrin M, Grippon P, Hoang C, Piette JC, Huraux JM, Opolon P. Cryoglobulinemia in chronic liver diseases: role of hepatitis C virus and liver damage. Gastroenterology 1994; 106:1291.
Simmonds P, Holmes EC, Cha TA, Chan SW, McOmish F, Irvine B, Beall E, Yap PL, Kolberg J, Urdea MS. Classification of hepatitis C virus into six major genotypes and a series of subtypes by phylogenetic analysis of the NS-5 region. J Gen Virol 1993; 74:2391.
Bukh J, Purcell RH, Miller RH. At least 12 genotypes of hepatitis C virus predicted by sequence analysis of the putative E1 gene of isolates collected worldwide. Proc Natl Acad Sci USA 1993; 90:8234.
Enomoto N, Sakuma I, Asahina Y, Kurosaki M, Murakami T, Yamamoto C, Ogura Y, Izumi N, Marumo F, Sato C. Mutations in the nonstructural protein 5A gene and response to interferon in patients with chronic hepatitis C virus 1b infection. N Engl J Med 1996; 334:77.
Yano M, Yatsuhashi H. HCV viral load, genotypes and efficacy of IFN therapy. Curr Ther 1993; 11:87.
Chemello L, Alberti A, Rose K, Simmonds P. Hepatitis C serotype and response to interferon therapy. N Engl J Med 1994; 330:143.
Zignego AL, Ferri C, Giannini C, Monti M, LaCivita L, Careccia G, Longombardo G, Lombardini F, Bombardieri S, Gentilini P. Hepatitis C virus genotypes analysis in patients with type II mixed cryoglobulinemia. Ann Intern Med 1996; 124:31.
American Rheumatism Association Glossary Committee. Dictionary of the rheumatic diseases, vol II. New York: Contact Associates, 1985.
Zehender G, DeMaddalena C, Monti G, Ballaré M, Saccardo F, Piconi S, Invernizzi F, Monteverde A, Galli M. HCV genotypes in bone marrow and peripheral blood mononuclear cells of patients with mixed cryoglobulinemia. Clin Exp Rheumatol 1995; 13 [Suppl 13]: S87.
Crovatto M, Ceselli S, Mazzaro C, Modolo ML, Martelli P, Mazzi G, Pozzato G, Giannini F, Barbisin M, Chiarotto B, Santini GF. HCV genotypes and cryoglobulinemia. Clin Exp Rheumatol 1995; 13 [Suppl 13]: S79.
Ferri C, LaCivita L, Cirafisi C, Siciliano G, Longombardo G, Bombardieri S, Rossi B. Peripheral neuropathy in mixed cryoglobulinemia: clinical and electrophysiologic investigations. J Rheumatol 1992; 19:889.
Gorevic PD, Kassab HJ, Levo Y, Kohn R, Meltzer M, Prose P, Franklin EC. Mixed cryoglobulinemia: clinical aspects and long-term follow-up of 40 patients. Am J Med 1980; 69:287.
Monti G, Galli M, Invernizzi F, Pioltelli P, Saccardo F, Monteverde A, Pietrogrande M, Renoldi P, Bombardieri S, Bordin G, Candela M, Ferri C, Gabrielli A, Mazzaro C, Migliaresi S, Mussini C, Ossi E, Quintiliani L, Tirri G, Vacca A and the Italian Group for the Study of Cryoglobulinemias. Cryoglobulinemias: a multi-centre study of the early clinical and laboratory manifestations of primary and secondary disease. Q J Med 1995; 88:115.
Bonetti B, Invernizzi F, Rizzuto N, Bonazzi ML, Zanusso GL, Chinaglia G, Monaco S. T-cell mediated epineurial vasculitis and humoral-mediated microangiopathy in cryoglobulinemic neuropathy. J Neuroimmunol 1997; 73:145.
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Origgi, L., Vanoli, M., Carbone, A. et al. Hepatitis C virus genotypes and clinical features in hepatitis C virus-related mixed cryoglobulinemia. Int J Clin Lab Res 28, 96–99 (1998). https://doi.org/10.1007/s005990050026
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/s005990050026