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Vol. 28. Issue. 3.July 2008
Pages 241-359
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Mixed cryoglobulinemia in patients with dual HCV/HIV infection: analysis of cryoprecipitate as a therapeutic decision tool
Crioglobulinemia mixta en pacientes con doble infección por VCH/VIH: análisis del crioprecipitado como herramienta de decisión terapéutica
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Simona Alexandrua, C.. Carameloa, A.. Montoyaa, R.. Garcíaa
a Servicio de Nefrología y Servicio de Inmunología, Fundación Jiménez Díaz-Capio. Universidad Autónoma, Madrid, Madrid, España,
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To the editor:

Infection by the hepatitis C virus (HCV) is the main cause of mixed cryoglobulinemia.1,2 However, the human immunodeficiency virus (HIV) also causes cryoglobulinemia.3 In highrisk people, dual HIV/HCV infection is common. The decision to add treatment for HCV to antiretroviral medication is difficult, because it may be harmful in immunodepressed individuals. A more precise diagnosis is also required because occult infection exists, with a falsely negative antibody test.4

In order to contribute to solve this problem, we studied cryoprecipitates from HIV-positive patients with cryoglobulinemia and membranoproliferative glomerulonephritis (MPGN). Serologic tests were positive for HIV/HCV in one patient, and for HIV alone in two patients.

The result was markedly clear: in the patient with dual infection, the cryoprecipitate only showed anti-HCV activity, while in the two patients with HIV infection alone, the cryoprecipitate only showed anti-HIV activity. These data allowed for taking the decision that only one patient had to be receive treatment for HCV.

CASE 1

A 45-year old male with HIV and HCV infection (genotype 1a) on antiretroviral therapy and with negative HIV load. In March 2007, the patient experienced nephrotic syndrome, and was diagnosed MPGN (table I). Cryoprecipitate was positive for HCV alone, and additional treatment with alpha-interferon was started.

CASE 2

A 36-year old male with HIV infection detected two years before and diagnosed of non-Hodgkin lymphoma in May 2006. He then had nephrotic syndrome with normal kidney function and positive cryoglobulins (table I). No antibodies to hepatitis C and B viruses were detected, and type I MPGN was diagnosed. Cryoprecipitate was positive for HIV and negative for HCV. Antiretroviral and chemotherapeutic therapy was started.

CASE 3

A 35-year old male with known HIV infection for eight years who showed nephrotic proteinuria, normal kidney function, and positive cryoglobulins (table I). A type I MPGN was diagnosed. HIV was only shown to be present in the cryoprecipitate, and treatment with antiretrovirals and steroids alone was started.

In all three cases, the cryoprecipitate was separated from the supernatant by centrifugation (3,000 rpm at 4 ºC), with adhered proteins being removed by washing with warm saline. Viral RNAs were extracted using Cobas-Amplipred (Roche). HIV and HCV loads were measured by RT-PCR using Cobas-Amplicor ultrasensitive for HIV-1 (limit, 50 copies/mL) and by PCR, using Taq Man 48 for HCV (limit, 10 IU/mL).

Several studies have shown the relationship between HIV and HCV infections, and the role of cryoglobulins in causing renal damage, particularly MPGN.5-9 It is unknown whether the higher percentage of cryoglobulinemia found in cases with dual HIV/HCV infection2 is due to one and/or the other virus.3 No reference has found in the literature with respects to the concomitant presence of both viral particles in the cryoprecipitate from patients with dual HIV/HCV infection.

Analysis of the cryoprecipitate is a useful tool for differential diagnosis of cryoglobulinemia in patients with dual HIV/HCV infection. It may also be used as a supplemental test to rule out a diagnosis in patients apparently monoinfected by HIV.

Bibliography
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Poynard T, Ratziu V, Benhamou Y, Opolon P, Cacoub P, Bedossa P. Natural history of HCV infection. Baillieres Best Pract Res Clin Gastroenterol 2000; 14: 11-28.
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Dezzutti CS, Astemborski J, Thomas DL, Marshall JH, Cabrera T, Purdy M, Vlahov D, Garfein RS. Prevalence of cryoglobulinemia in hepatitis C virus (HCV) positive patients with and without human immunodeficiency virus (HIV) coinfection. J Clin Virol 2004; 31: 210-214. [Pubmed]
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Bonnet F, Pineau JJ, Taupin JL, Feyley A, Bonarek M, De Witte S, Bernard N, Lacoste D, Morlat P, Beylot J. Prevalence of cryoglobulinemia and serological markers of autoimmunity in human immunodeficiency virus infected individuals: a cross-sectional study of 97 patients. J Rheumatol 2003; 30:2005-10. [Pubmed]
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Bonacini M, Lin HJ, Hollinger FB. Effect of coexisting HIV-1 infection on the diagnosis and evaluation of hepatitis C virus. J Acquir Immune Defic Syndr 2001; 26: 340-4. [Pubmed]
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Germtholtz TE, Goetsch SJW and Katz I. HIV-related nephropathy: A south african perspective. Kidney Int 2006; 69: 1885-1891. [Pubmed]
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Sabry AA, Sobh MA, Irving WL y cols. A comprehensive study of the association between hepatitis C virus and glomerulopathy. NDT 2002; 17: 239-245. [Pubmed]
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Johnson RF, Gretch DR, Yamabe H y cols. Membranoproliferative glomerulonephritis associated with hepatitis C virus infection. N Engl J Med 1993; 328: 465-470. [Pubmed]
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Chidambaram M, Stigant CE, Sugar LM, Rames Prasad GV. Type I membrano proliferative glomerulonephritis in an HIV-infected individual without hepatitis C co-infection. Clin Nephrol 2002; 57: 154-7. [Pubmed]
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Hoch B, Juknevicius I, Liapis H. Glomerular injury associated with hepatitis C infection: a correlation with blood and tissue HCVPCR. Semin Diagn Pathol 2002; 19: 175-87. [Pubmed]
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