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Advances in Medical Sciences

The Journal of Medical University of Bialystok

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Extrahepatic manifestations associated with chronic hepatitis C infections in Poland

D Zarebska-Michaluk1 / D Lebensztejn1 / W Kryczka1, / E Skiba1,

Department of Infectious Diseases, Provincial Hospital, Kielce, Poland1

Department of Pediatrics, Gastroenterology and Allergology, Medical University of Bialystok, Bialystok, Poland2

Institute of Medical Education, Swietokrzyska Academy, Kielce, Poland3

Department of Pediatric Oncology and Hematology, Medical University of Bialystok, Bialystok, Poland4

This content is open access.

Citation Information: Advances in Medical Sciences. Volume 55, Issue 1, Pages 67–73, ISSN (Online) 1898-4002, ISSN (Print) 1896-1126, DOI: 10.2478/v10039-010-0009-4, April 2010

Publication History

Published Online:

Extrahepatic manifestations associated with chronic hepatitis C infections in Poland

Purpose: To assess the prevalence and predictive factors of extrahepatic manifestation (EM) in patients with chronic hepatitis C (CHC) infection in Poland.

Material and Methods: 340 consecutive patients (mean age: 42 years) with untreated CHC were studied between 2000 and 2006. The HCV infection was defined by positive serology and serum HCV RNA. The inflammation grade and fibrosis stage were assessed according to Ishak. Demographic, laboratory and liver biopsy data were collected. The patients with liver cirrhosis, concomitant HBV or HIV infection, autoimmune liver diseases and alcohol abusers were excluded from the analysis.

Results: 210 patients with CHC (61.7%) presented at least 1 extrahepatic manifestation, including mixed cryoglobulinemia (37.1%), thrombocytopenia (27.6%), thyroid autoimmunity (16.2%), dermatological disorders (4.1%) and type 2 diabetes (4.1%). Other EM such as the sicca syndrome, nephropathy, polyneuropathy and B-cell lymphoma were observed in single cases. In multivariate analysis lower platelet count was found as a predictive factor of EM in patients with CHC.

Conclusions: The majority of patients with CHC, living in Poland, have EM, of which cryoglobulinemia, thrombocytopenia, thyroid autoimmunity, dermatological disorders and type 2 diabetes are most common. Through the multivariate analysis the lower platelet predicts extrahepatic manifestations associated with chronic hepatitis C.

Keywords: hepatitis C; extrahepatic manifestation; cryoglobulinemia; thrombocytopenia; thyroid autoimmunity

  • Hadziyannis SJ. The spectrum of extrahepatic manifestations in hepatitis C virus infection. J Viral Hepat. 1997 Jan;4(1):9-28. [PubMed]

  • Manns MP, Rambusch EG. Autoimmunity and extrahepatic manifestations in hepatitis C virus infection. J Hepatol. 1999;31 Suppl 1:39-42. [CrossRef] [PubMed]

  • Sène D, Limal N, Cacoub P. Hepatitis C virus-associated extrahepatic manifestations: a review. Metab Brain Dis. 2004 Dec;19(3-4):357-81. [CrossRef] [PubMed]

  • El-Serag HB, Hampel H, Yeh C, Rabeneck L. Extrahepatic manifestations of hepatitis C among United States male veterans. Hepatology. 2002 Dec;36(6):1439-45.

  • Zignego AL, Bréchot C. Extrahepatic manifestations of HCV infection: facts and controversies. J Hepatol. 1999 Aug;31(2):369-76. [PubMed] [CrossRef]

  • Ishak K, Baptista A, Bianchi L, Callea F, De Groote J, Gudat F, Denk H, Desmet V, Korb G, MacSween RN, et al. Histological grading and staging of chronic hepatitis. J Hepatol. 1995 Jun;22(6):696-9. [CrossRef] [PubMed]

  • Pascual M, Perrin L, Giostra E, Schifferli JA. Hepatitis C virus in patients with cryoglobulinemia type II. J Infect Dis. 1990 Aug;162(2):569-70. [CrossRef] [PubMed]

  • Cacoub P, Poynard T, Ghillani P, Charlotte F, Olivi M, Piette JC, Opolon P. Extrahepatic manifestations of chronic hepatitis C. MULTIVIRC Group. Multidepartment Virus C. Arthritis Rheum. 1999 Oct;42(10):2204-12. [PubMed] [CrossRef]

  • Cacoub P, Renou C, Rosenthal E, Cohen P, Loury I, Loustaud-Ratti V, Yamamoto AM, Camproux AC, Hausfater P, Musset L, Veyssier P, Raguin G, Piette JC. Extrahepatic manifestations associated with hepatitis C virus infection. A prospective multicenter study of 321 patients. The GERMIVIC. Groupe d'Etude et de Recherche en Medecine Interne et Maladies Infectieuses sur le Virus de l'Hepatite C. Medicine (Baltimore). 2000 Jan;79(1):47-56. [CrossRef]

  • Ignatova TM, Aprosina ZG, Serov VV, Mukhin NA, Krel' PE, Semenkova EN, Popova IV, Tanashchuk EL. Extrahepatic manifestations of chronic hepatitis C. Ter Arkh. 1998;70(11):9-16. [PubMed]

  • Nagao Y, Tanaka J, Nakanishi T, Moriya T, Katayama K, Kumagai J, Komiya Y, Itoh Y, Myoken Y, Fujihara M, Sata M, Yoshizawa H. High incidence of extrahepatic manifestations in an HCV hyperendemic area. Hepatol Res. 2002 Jan;22(1):27-36. [CrossRef]

  • Pellicano R, Leone N, Maiocco IA, Modena V, Arena V, Marietti G, Puiatti P, Palmas F, Rizzetto M, Ponzetto A. Chronic HCV hepatopathy and cryoglobulinemia. The associated clinical spectrum. Minerva Med. 1999 Jan-Feb;90(1-2):1-5. [PubMed]

  • Liakina V, Speiciene D, Irnius A, Naraskeviciene J, Barakauskiene A, Semuchiniene T. Prevalence of cryoglobulinemia in patients with chronic HCV infection. Med Sci Monit. 2002 Jan;8(1):CR31-6. [PubMed]

  • Jabłońska J, Zabek J, Kozłowska J, Cianciara J. Immunological disorders in patients with chronic viral hepatitis type C. Przegl Epidemiol. 2001;55(4):459-64. [PubMed]

  • Friedman SL. Cellular networks in hepatic fibrosis. Digestion. 1998 Jul-Aug;59(4):368-71. [PubMed] [CrossRef]

  • Hadziyannis SJ. Skin diseases associated with hepatitis C virus infection. J Eur Acad Dermatol Venereol. 1998 Jan;10(1):12-21. [CrossRef] [PubMed]

  • Pawlotsky JM, Ben Yahia M, Andre C, Voisin MC, Intrator L, Roudot-Thoraval F, Deforges L, Duvoux C, Zafrani ES, Duval J, et al. Immunological disorders in C virus chronic active hepatitis: a prospective case-control study. Hepatology. 1994 Apr;19(4):841-8. [CrossRef]

  • Weiner SM, Berg T, Berthold H, Weber S, Peters T, Blum HE, Hopf U, Peter HH. A clinical and virological study of hepatitis C virus-related cryoglobulinemia in Germany. J Hepatol. 1998 Sep;29(3):375-84. [CrossRef] [PubMed]

  • Donada C, Crucitti A, Donadon V, Tommasi L, Zanette G, Crovatto M, Santini GF, Chemello L, Alberti A. Systemic manifestations and liver disease in patients with chronic hepatitis C and type II or III mixed cryoglobulinaemia. J Viral Hepat. 1998 May;5(3):179-85. [PubMed]

  • Fayyazi A, Schott P, Hartmann H, Mihm S, Middel P, Ramadori G, Radzun HJ. Clinical, biochemical, and histological changes in hepatitis C virus infection-associated cryoglobulinemia. Z Gastroenterol. 1997 Oct;35(10):921-8. [PubMed]

  • Lunel F, Musset L, Cacoub P, Frangeul L, Cresta P, Perrin M, Grippon P, Hoang C, Valla D, Piette JC, et al. Cryoglobulinemia in chronic liver diseases: role of hepatitis C virus and liver damage. Gastroenterology. 1994 May;106(5):1291-300. Erratum in: Gastroenterology 1995 Feb;108(2):620.

  • Naarendorp M, Kallemuchikkal U, Nuovo GJ, Gorevic PD. Longterm efficacy of interferon-alpha for extrahepatic disease associated with hepatitis C virus infection. J Rheumatol. 2001 Nov;28(11):2466-73. [PubMed]

  • Wang CS, Yao WJ, Wang ST, Chang TT, Chou P. Strong association of hepatitis C virus (HCV) infection and thrombocytopenia: implications from a survey of a community with hyperendemic HCV infection. Clin Infect Dis. 2004 Sep 15;39(6):790-6.

  • Nakajima H, Takagi H, Yamazaki Y, Toyoda M, Takezawa J, Nagamine T, Mori M. Immune thrombocytopenic purpura in patients with hepatitis C virus infection. Hepatogastroenterology. 2005 Jul-Aug;52(64):1197-200. [PubMed]

  • Rajan SK, Espina BM, Liebman HA. Hepatitis C virus-related thrombocytopenia: clinical and laboratory characteristics compared with chronic immune thrombocytopenic purpura. Br J Haematol. 2005 Jun;129(6):818-24. [CrossRef] [PubMed]

  • Benci A, Caremani M, Tacconi D. Thrombocytopenia in patients with HCV-positive chronic hepatitis: efficacy of leucocyte interferon-alpha treatment. Int J Clin Pract. 2003 Jan-Feb;57(1):17-9. [PubMed]

  • Antonelli A, Ferri C, Pampana A, Fallahi P, Nesti C, Pasquini M, Marchi S, Ferrannini E. Thyroid disorders in chronic hepatitis C. Am J Med. 2004 Jul 1;117(1):10-3. [PubMed] [CrossRef]

  • Ganne-Carrie N, Medini A, Coderc E, Seror O, Christidis C, Grimbert S, Trinchet JC, Beaugrand M. Latent autoimmune thyroiditis in untreated patients with HCV chronic hepatitis: a case-control study. J Autoimmun. 2000 Mar;14(2):189-93. [CrossRef]

  • Tran A, Quaranta JF, Benzaken S, Thiers V, Chau HT, Hastier P, Regnier D, Dreyfus G, Pradier C, Sadoul JL, et al. High prevalence of thyroid autoantibodies in a prospective series of patients with chronic hepatitis C before interferon therapy. Hepatology. 1993 Aug;18(2):253-7. [CrossRef]

  • Marazuela M, García-Buey L, González-Fernández B, García-Monzón C, Arranz A, Borque MJ, Moreno-Otero R. Thyroid autoimmune disorders in patients with chronic hepatitis C before and during interferon-alpha therapy. Clin Endocrinol (Oxf). 1996 Jun;44(6):635-42. [CrossRef]

  • Peoc'h K, Dubel L, Chazouillères O, Ocwieja T, Duron F, Poupon R, Johanet C. Polyspecificity of antimicrosomal thyroid antibodies in hepatitis C virus-related infection. Am J Gastroenterol. 2001 Oct;96(10):2978-83.

  • Custro N, Montalto G, Scafidi V, Soresi M, Gallo S, Tripi S, Notarbartolo A. Prospective study on thyroid autoimmunity and dysfunction related to chronic hepatitis C and interferon therapy. J Endocrinol Invest. 1997 Jul-Aug;20(7):374-80. [PubMed]

  • Antonelli A, Ferri C, Fallahi P, Pampana A, Ferrari SM, Goglia F, Ferrannini E. Hepatitis C virus infection: evidence for an association with type 2 diabetes. Diabetes Care. 2005 Oct;28(10):2548-50. [CrossRef] [PubMed]

  • Caronia S, Taylor K, Pagliaro L, Carr C, Palazzo U, Petrik J, O'Rahilly S, Shore S, Tom BD, Alexander GJ. Further evidence for an association between non-insulin-dependent diabetes mellitus and chronic hepatitis C virus infection. Hepatology. 1999 Oct;30(4):1059-63. [CrossRef] [PubMed]

  • Mangia A, Schiavone G, Lezzi G, Marmo R, Bruno F, Villani MR, Cascavilla I, Fantasia L, Andriulli A. HCV and diabetes mellitus: evidence for a negative association. Am J Gastroenterol. 1998 Dec;93(12):2363-7. [CrossRef] [PubMed]

  • Antonelli A, Ferri C, Ferrari SM, Colaci M, Fallahi P. Immunopathogenesis of HCV-related endocrine manifestations in chronic hepatitis and mixed cryoglobulinemia. Autoimmun Rev. 2008 Oct;8(1):18-23. [PubMed] [CrossRef] [Web of Science]

  • Antonelli A, Ferri C, Ferrari SM, Colaci M, Sansonno D, Fallahi P. Endocrine manifestations of hepatitis C virus infection. Nat Clin Pract Endocrinol Metab. 2009 Jan;5(1):26-34. [CrossRef] [PubMed]

  • Paoletti V, Mammarella A, Basili S, Paradiso M, Di Franco M, De Matteis A, Musca A. Prevalence and clinical features of skin diseases in chronic HCV infection. A prospective study in 96 patients. Panminerva Med. 2002 Dec;44(4):349-52. [PubMed]

  • Haddad J, Deny P, Munz-Gotheil C, Ambrosini JC, Trinchet JC, Pateron D, Mal F, Callard P, Beaugrand M. Lymphocytic sialadenitis of Sjögren's syndrome associated with chronic hepatitis C virus liver disease. Lancet. 1992 Feb 8;339(8789):321-3.

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