The presence of non-organ-specific autoantibodies is associated with a negative response to combination therapy with interferon and ribavirin for chronic hepatitis C

BMC Infectious Diseases

Frank Lammert²  Siegfried Matern²  Johann Lorenzen¹  Carsten Gartung²  Christoph G Dietrich²  Andreas Geier²  Christian Stolte²  Hermann E Wasmuth² 

[1] Institute of Pathology, University Hospital Aachen (UKA), Aachen University (RWTH), Aachen, Germany;Department of Internal Medicine III, University Hospital Aachen (UKA), Aachen University (RWTH), Aachen, Germany

关键词: ribavirin;    non-organ-specific autoantibodies;    interferon-α;    chronic hepatitis C;    Antiviral therapy;   

Others  :  1177104
DOI  :  10.1186/1471-2334-4-4

 received in 2003-09-06, accepted in 2004-02-13,  发布年份 2004

【 摘 要 】

Background

Non-organ-specific autoantibodies are found in a considerable number of anti-HCV positive patients. Previous studies investigated the clinical relevance of these antibodies in patients treated with interferon monotherapy, but not combination therapies.

Methods

Anti-nuclear, anti-smooth muscle, anti-mitochondrial, anti-neutrophil-cytoplasmatic and anti-liver/kidney microsomal antibodies were determined in 78 consecutive anti-HCV positive patients by indirect immunofluorescence. The presence of these antibodies was related to demographic variables and to the outcome of antiviral combination therapy with interferon-α and ribavirin in 65 patients.

Results

In our study, positivity for autoantibodies was associated with higher alanine aminotransferase levels and higher mean values for HCV-RNA (p < 0.01). Furthermore, negativity for non-organ-specific autoantibodies was associated with a favourable treatment outcome of combination therapy with at least one negative RT-PCR for HCV-RNA during treatment (OR 4.65, 95% CI 1.31 to 16.48, p = 0.02). ANA and SMA staining patterns and titers were not correlated to treatment response. With multiple logistic regression analysis, positivity for autoantibodies and HCV genotype were independently associated with outcome of antiviral combination therapy (p = 0.02).

Conclusions

The absence of non-organ-specific autoantibodies might indicate a significantly higher chance for viral clearance in response to combination therapy for chronic hepatitis C infection. Therefore, despite of an overall higher treatment response, the addition of the immunomodulatory drug ribavirin could accentuate immunological differences that affect treatment outcome and might have been less obvious in earlier studies analysing interferon monotherapy.

【 授权许可】

   
2004 Wasmuth et al; licensee BioMed Central Ltd. This is an Open Access article: verbatim copying and redistribution of this article are permitted in all media for any purpose, provided this notice is preserved along with the article's original URL.

【 图 表 】

Figure 1.

Figure 2.

【 参考文献 】

• [1]Manns MP, Rambusch EG: Autoimmunity and extrahepatic manifestations in hepatitis C virus infection. J Hepatol 1999, 31 Suppl 1:39-42.
• [2]Zauli D, Cassani F, Bianchi FB: Auto-antibodies in hepatitis C. Biomed Pharmacother 1999, 53:234-241.
• [3]Lopes EP, Silva AE, Sette Junior H, Guimaraes RX, Ferraz ML: Autoantibodies before, during and after administration of recombinant interferon-alpha for chronic viral hepatitis. Rev Inst Med Trop Sao Paulo 1995, 37:455-460.
• [4]Bayraktar Y, Bayraktar M, Gurakar A, Hassanein TI, Van Thiel DH: A comparison of the prevalence of autoantibodies in individuals with chronic hepatitis C and those with autoimmune hepatitis: the role of interferon in the development of autoimmune diseases. Hepatogastroenterology 1997, 44:417-425.
• [5]Fang SH, Hwang LH, Chen DS, Chiang BL: Ribavirin enhancement of hepatitis C virus core antigen-specific type 1 T helper cell response correlates with the increased IL-12 level. J Hepatol 2000, 33:791-798.
• [6]Tam RC, Pai B, Bard J, Lim C, Averett DR, Phan UT, Milovanovic T: Ribavirin polarizes human T cell responses towards a Type 1 cytokine profile. J Hepatol 1999, 30:376-382.
• [7]Cassani F, Cataleta M, Valentini P, Muratori P, Giostra F, Francesconi R, Muratori L, Lenzi M, Bianchi G, Zauli D, Bianchi FB: Serum autoantibodies in chronic hepatitis C: comparison with autoimmune hepatitis and impact on the disease profile. Hepatology 1997, 26:561-566.
• [8]Noda K, Enomoto N, Arai K, Masuda E, Yamada Y, Suzuki K, Tanaka M, Yoshihara H: Induction of antinuclear antibody after interferon therapy in patients with type-C chronic hepatitis: its relation to the efficacy of therapy. Scand J Gastroenterol 1996, 31:716-722.
• [9]National Institutes of Health Consensus Development Conference Statement: Management of hepatitis C 2002 (June 10-12, 2002) Gastroenterology 2002, 123:2082-2099.
• [10]Alvarez F, Berg PA, Bianchi FB, Bianchi L, Burroughs AK, Cancado EL, Chapman RW, Cooksley WG, Czaja AJ, Desmet VJ, Donaldson PT, Eddleston AL, Fainboim L, Heathcote J, Homberg JC, Hoofnagle JH, Kakumu S, Krawitt EL, Mackay IR, MacSween RN, Maddrey WC, Manns MP, McFarlane IG, Meyer zum Buschenfelde KH, Zeniya M, et al.: International Autoimmune Hepatitis Group Report: review of criteria for diagnosis of autoimmune hepatitis. J Hepatol 1999, 31:929-938.
• [11]Batts KP, Ludwig J: Chronic hepatitis. An update on terminology and reporting. Am J Surg Pathol 1995, 19:1409-1417.
• [12]Bottazzo GF, Florin-Christensen A, Fairfax A, Swana G, Doniach D, Groeschel-Stewart U: Classification of smooth muscle autoantibodies detected by immunofluorescence. J Clin Pathol 1976, 29:403-410.
• [13]Cassani F, Bianchi FB, Lenzi M, Volta U, Pisi E: Immunomorphological characterisation of antinuclear antibodies in chronic liver disease. J Clin Pathol 1985, 38:801-805.
• [14]Piazzolla G, Tortorella C, Fiore G, Fanelli M, Pisconti A, Antonaci S: Interleukin-12 p40/p70 ratio and in vivo responsiveness to IFN-alpha treatment in chronic hepatitis C. J Interferon Cytokine Res 2001, 21:453-461.
• [15]Fang SH, Lai MY, Hwang LH, Yang PM, Chen PJ, Chiang BL, Chen DS: Ribavirin enhances interferon-gamma levels in patients with chronic hepatitis C treated with interferon-alpha. J Biomed Sci 2001, 8:484-491.
• [16]Lenzi M, Bellentani S, Saccoccio G, Muratori P, Masutti F, Muratori L, Cassani F, Bianchi FB, Tiribelli C: Prevalence of non-organ-specific autoantibodies and chronic liver disease in the general population: a nested case-control study of the Dionysos cohort. Gut 1999, 45:435-441.
• [17]Grimbert S, Johanet C, Bendjaballah F, Homberg JC, Poupon R, Beaugrand M: Antimitochondrial antibodies in patients with chronic hepatitis C. Liver 1996, 16:161-165.
• [18]Dalekos GN, Tsianos EV: Anti-neutrophil antibodies in chronic viral hepatitis. J Hepatol 1994, 20:561.
• [19]Dalekos GN, Makri E, Loges S, Obermayer-Straub P, Zachou K, Tsikrikas T, Schmidt E, Papadamou G, Manns MP: Increased incidence of anti-LKM autoantibodies in a consecutive cohort of hepatitis C patients from central Greece. Eur J Gastroenterol Hepatol 2002, 14:35-42.
• [20]Vella FS, Orlando P, Attanasi F, Simone B, Mundo A, Lopalco P, Schiraldi O, Antonaci S: [Autoantibodies in chronic hepatitis C. Markers of autoimmunity or non-specific events?]. Recenti Prog Med 2001, 92:107-112.
• [21]Peng YC, Hsieh SC, Yang DY, Tung CF, Hu WH, Huang WN, Chen GH: Expression and clinical significance of antinuclear antibody in hepatitis C virus infection. J Clin Gastroenterol 2001, 33:402-406.
• [22]Muratori P, Muratori L, Stroffolini T, Pappas G, Terlizzi P, Ferrari R, Loffreda S, Cassani F, Rapicetta M, Guadagnino V, Bianchi FB, Lenzi M: Prevalence of non-organ specific autoantibodies in HCV-infected subjects in the general population. Clin Exp Immunol 2003, 131:118-121.
• [23]Wada M, Kang KB, Kinugasa A, Shintani S, Sawada K, Nishigami T, Shimoyama T: Does the presence of serum autoantibodies influence the responsiveness to interferon-alpha 2a treatment in chronic hepatitis C? Intern Med 1997, 36:248-254.
• [24]Carella C, Mazziotti G, Morisco F, Rotondi M, Cioffi M, Tuccillo C, Sorvillo F, Caporaso N, Amato G: The addition of ribavirin to interferon-alpha therapy in patients with hepatitis C virus-related chronic hepatitis does not modify the thyroid autoantibody pattern but increases the risk of developing hypothyroidism. Eur J Endocrinol 2002, 146:743-749.
• [25]McFarlane IG: Autoimmune hepatitis: diagnostic criteria, subclassifications, and clinical features. Clin Liver Dis 2002, 6:317-333.
• [26]Strassburg CP, Manns MP: Autoantibodies and autoantigens in autoimmune hepatitis. Semin Liver Dis 2002, 22:339-352.
• [27]Heathcote J: Variant syndromes of autoimmune hepatitis. Clin Liver Dis 2002, 6:381-396.