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Viral Hepatitis

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Cryoglobulinemia is associated with steatosis and fibrosis in chronic hepatitis C†

  1. David Saadoun1,‡,
  2. Tarik Asselah2,‡,
  3. Mathieu Resche-Rigon3,
  4. Frédéric Charlotte4,
  5. Pierre Bedossa5,
  6. Dominique Valla2,
  7. Jean-Charles Piette1,
  8. Patrick Marcellin2,
  9. Patrice Cacoub1,§,*

Article first published online: 25 MAY 2006

DOI: 10.1002/hep.21190

Issue

Hepatology

Hepatology

Volume 43, Issue 6, pages 1337–1345, June 2006

Additional Information

How to Cite

Saadoun, D., Asselah, T., Resche-Rigon, M., Charlotte, F., Bedossa, P., Valla, D., Piette, J.-C., Marcellin, P. and Cacoub, P. (2006), Cryoglobulinemia is associated with steatosis and fibrosis in chronic hepatitis C. Hepatology, 43: 1337–1345. doi: 10.1002/hep.21190

Author Information

  1. 1

    Service de Médecine Interne and CNRS UMR 7087, Hôpital Pitié-Salpétrière, Paris, France

  2. 2

    Service d'Hépatologie and INSERM CRB 3, Hôpital Beaujon, Clichy, France

  3. 3

    Département de Biostatistique et Informatique Médicale, Hôpital Saint-Louis, Paris, France

  4. 4

    Service d'Anatomo-Pathologie, Hôpital Pitié-Salpétrière, Paris, France

  5. 5

    Service d'Anatomo-Pathologie, Hôpital Beaujon, Clichy, France

  1. ‡

    D. Saadoun and T. Asselah contributed equally to this study.

  2. §

    fax: (33)1-42-17-80-33

*Department of Internal Medicine, Hôpital La Pitié-Salpêtrière, 83, Boulevard de l'Hôpital, 75651 Cedex 13 Paris, France

  1. †

    Potential conflict of interest: Nothing to report.

  2. ‡

    D. Saadoun and T. Asselah contributed equally to this study.

  3. §

    fax: (33)1-42-17-80-33

Publication History

  1. Issue published online: 25 MAY 2006
  2. Article first published online: 25 MAY 2006
  3. Manuscript Accepted: 15 MAR 2006
  4. Manuscript Received: 14 NOV 2005

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References

  • 1
    Wasley A, Alter MJ. Epidemiology of hepatitis C: geographic differences and temporal trends. Semin Liver Dis 2000; 20: 1-16.
  • 2
    Marcellin P, Asselah T, Boyer N. Fibrosis and disease progression in hepatitis C. HEPATOLOGY 2002; 36(5B): S47-S56.
  • 3
    Gorevic PD, Kassab HJ, Levo Y, Kohn R, Meltzer M, Prose P, et al. Mixed cryoglobulinemia: clinical aspects and long-term follow-up of 40 patients. Am J Med 1980; 69: 287-308.
  • 4
    Cacoub P, Poynard T, Ghillani P, Charlotte F, Olivi M, Piette JC, et al. Extrahepatic manifestations of chronic hepatitis C. MULTIVIRC Group. Multidepartment Virus C. Arthritis Rheum 1999; 42: 2204-2212.
    Direct Link:
  • 5
    Kayali Z, Buckwold VE, Zimmerman B, Schmidt WN. Hepatitis C, cryoglobulinemia, and cirrhosis: a meta-analysis. HEPATOLOGY 2002; 36: 978-985.
  • 6
    Lunel F, Musset L, Cacoub P, Frangeul L, Cresta P, Perrin M, et al. Cryoglobulinemia in chronic liver diseases: role of hepatitis C virus and liver damage. Gastroenterology 1994; 106: 1291-1300.
  • 7
    Castera L, Hezode C, Roudot-Thoraval F, Bastie A, Zafrani ES, Pawlotsky JM, et al. Worsening of steatosis is an independent factor of fibrosis progression in untreated patients with chronic hepatitis C and paired liver biopsies. Gut 2003; 52: 288-292.
  • 8
    Poynard T, Ratziu V, McHutchison J, Manns M, Goodman Z, Zeuzem S, et al. Effect of treatment with peginterferon or interferon alfa-2b and ribavirin on steatosis in patients infected with hepatitis C. HEPATOLOGY 2003; 38: 75-85.
    Direct Link:
  • 9
    Patton HM, Patel K, Behling C, Bylund D, Blatt LM, Vallee M, et al. The impact of steatosis on disease progression and early and sustained treatment response in chronic hepatitis C patients. J Hepatol 2004; 40: 484-490.
  • 10
    Hourigan LF, Macdonald GA, Purdie D, Whitehall VH, Shorthouse C, Clouston A, et al. Fibrosis in chronic hepatitis C correlates significantly with body mass index and steatosis. HEPATOLOGY 1999; 29: 1215-1219.
    Direct Link:
  • 11
    Westin J, Nordlinder H, Lagging M, Norkrans G, Wejstal R. Steatosis accelerates fibrosis development over time in hepatitis C virus genotype 3 infected patients. J Hepatol 2002; 37: 837-842.
  • 12
    Mihm S, Fayyazi A, Hartmann H, Ramadori G. Analysis of histopathological manifestations of chronic hepatitis C virus infection with respect to virus genotype. HEPATOLOGY 1997; 25: 735-739.
    Direct Link:
  • 13
    Adinolfi LE, Gambardella M, Andreana A, Tripodi MF, Utili R, Ruggiero G. Steatosis accelerates the progression of liver damage of chronic hepatitis C patients and correlates with specific HCV genotype and visceral obesity. HEPATOLOGY 2001; 33: 1358-1364.
    Direct Link:
  • 14
    Rubbia-Brandt L, Quadri R, Abid K, Giostra E, Male PJ, Mentha G, et al. Hepatocyte steatosis is a cytopathic effect of hepatitis C virus genotype 3. J Hepatol 2000; 33: 106-115.
  • 15
    Agnello V. The etiology and pathophysiology of mixed cryoglobulinemia secondary to hepatitis C virus infection. Springer Semin Immunopathol 1997; 19: 111-129.
  • 16
    Musset L, Diemert MC, Taibi F, Thi Huong Du L, Cacoub P, Leger JM, et al. Characterization of cryoglobulins by immunoblotting. Clin Chem 1992; 38: 798-802.
  • 17
    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: 837-856.
  • 18
    Brouet JC, Clauvel JP, Danon F, Klein M, Seligmann M. Biologic and clinical significance of cryoglobulins. A report of 86 cases. Am J Med 1974; 57: 775-788.
  • 19
    Stuyver L, Rossau R, Wyseur A, Duhamel M, Vanderborght B, Van Heuverswyn H, et al. Typing of hepatitis C virus isolates and characterization of new subtypes using a line probe assay. J Gen Virol 1993; 74(Pt 6): 1093-1102.
  • 20
    Detmer J, Lagier R, Flynn J, Zayati C, Kolberg J, Collins M, et al. Accurate quantification of hepatitis C virus (HCV) RNA from all HCV genotypes by using branched-DNA technology. J Clin Microbiol 1996; 34: 901-907.
  • 21
    Bedossa P, Poynard T. An algorithm for the grading of activity in chronic hepatitis C. The METAVIR Cooperative Study Group. HEPATOLOGY 1996; 24: 289-293.
    Direct Link:
  • 22
    Agnello V, Abel G. Localization of hepatitis C virus in cutaneous vasculitic lesions in patients with type II cryoglobulinemia. Arthritis Rheum 1997; 40: 2007-2015.
    Direct Link:
  • 23
    Loffreda S, Muratori P, Muratori L, Mele L, Bianchi FB, Lenzi M. Enhanced monocyte Th1 cytokine production in HCV-infected cryoglobulinemic patients. J Hepatol 2003; 38: 230-236.
  • 24
    Saadoun D, Boyer O, Trebeden-Negre H, Limal N, Bon-Durand V, Andreu M, et al. Predominance of type 1 (Th1) cytokine production in the liver of patients with HCV-associated mixed cryoglobulinemia vasculitis. J Hepatol 2004; 41: 1031-1037.
  • 25
    Monto A, Alonzo J, Watson JJ, Grunfeld C, Wright TL. Steatosis in chronic hepatitis C: relative contributions of obesity, diabetes mellitus, and alcohol. HEPATOLOGY 2002; 36: 729-736.
    Direct Link:
  • 26
    Rubbia-Brandt L, Fabris P, Paganin S, Leandro G, Male PJ, Giostra E, et al. Steatosis affects chronic hepatitis C progression in a genotype specific way. Gut 2004; 53: 406-412.
  • 27
    Asselah T, Boyer N, Guimont MC, Cazals-Hatem D, Tubach F, Nahon K, Daikha H, et al. Liver fibrosis is not associated with steatosis but with necroinflammation in French patients with chronic hepatitis C. Gut 2003; 52: 1638-1643.
  • 28
    Clark JM, Brancati FL, Diehl AM. Nonalcoholic fatty liver disease. Gastroenterology 2002; 122: 1649-1657.
  • 29
    Czaja AJ, Carpenter HA, Santrach PJ, Moore SB. Host- and disease-specific factors affecting steatosis in chronic hepatitis C. J Hepatol 1998; 29: 198-206.
  • 30
    Asselah T, Rubbia-Brandt L, Marcellin P, Negro F. Steatosis in chronic hepatitis C: why does it really matter? Gut 2006; 55: 123-130.
  • 31
    Adinolfi LE, Utili R, Attanasio V, Zampino R, Ragone E, Tripodi MF, et al. Epidemiology, clinical spectrum and prognostic value of mixed cryoglobulinaemia in hepatitis C virus patients: a prospective study. Ital J Gastroenterol 1996; 28: 1-9.
  • 32
    Hui JM, Kench J, Farrell GC, Lin R, Samarasinghe D, Liddle C, et al. Genotype-specific mechanisms for hepatic steatosis in chronic hepatitis C infection. J Gastroenterol Hepatol 2002; 17: 873-881.
    Direct Link:
  • 33
    Serfaty L, Andreani T, Giral P, Carbonell N, Chazouilleres O, Poupon R. Hepatitis C virus induced hypobetalipoproteinemia: a possible mechanism for steatosis in chronic hepatitis C. J Hepatol 2001; 34: 428-434.
  • 34
    Clark JM, Diehl AM. Hepatic steatosis and type 2 diabetes mellitus. Curr Diab Rep 2002; 2: 210-215.
  • 35
    Weiner SM, Berg T, Berthold H, Weber S, Peters T, Blum HE, et al. A clinical and virological study of hepatitis C virus-related cryoglobulinemia in Germany. J Hepatol 1998; 29: 375-384.
  • 36
    Zignego AL, Ferri C, Giannini C, Monti M, La Civita L, Careccia G, et al. Hepatitis C virus genotype analysis in patients with type II mixed cryoglobulinemia. Ann Intern Med 1996; 124: 31-34.
  • 37
    Liaw YF, Lee CS, Tsai SL, Liaw BW, Chen TC, Sheen IS, et al. T-cell–mediated autologous hepatocytotoxicity in patients with chronic hepatitis C virus infection. HEPATOLOGY 1995; 22: 1368-1373.
  • 38
    Boyer O, Saadoun D, Abriol J, Dodille M, Piette JC, Cacoub P, et al. CD4+CD25+ regulatory T-cell deficiency in patients with hepatitis C-mixed cryoglobulinemia vasculitis. Blood 2004; 103: 3428-3430.
  • 39
    Bataller R, Brenner DA. Liver fibrosis. J Clin Invest 2005; 115: 209-218.
  • 40
    Novobrantseva TI, Majeau GR, Amatucci A, Kogan S, Brenner I, Casola S, et al. Attenuated liver fibrosis in the absence of B cells. J Clin Invest 2005; 115: 3072-3082.
  • 41
    Sansonno D, Lauletta G, De Re V, Tucci FA, Gatti P, Racanelli V, et al. Intrahepatic B cell clonal expansions and extrahepatic manifestations of chronic HCV infection. Eur J Immunol 2004; 34: 126-136.
    Direct Link:
  • 42
    Intraobserver and interobserver variations in liver biopsy interpretation in patients with chronic hepatitis C. The French METAVIR Cooperative Study Group. HEPATOLOGY 1994; 20: 15-20.
    Direct Link:
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