Non-organ-specific autoantibodies in chronic hepatitis C patients: Association with histological activity and fibrosis P. Chre ´ tien a, * , M. Chousterman b , I. Abd Alsamad c , V. Ozenne b , I. Rosa b , C. Barrault b , T. Lons b , H. Hage `ge b a Laboratoire d’immunologie, Centre Hospitalier intercommunal de Cre ´teil, 40 avenue de Verdun, 94010 Cre ´teil Ce ´dex, France b Service de gastroente´rologie, Centre Hospitalier Intercommunal de Cre ´teil, 40 avenue de Verdun, 94010 Cre ´teil Ce´dex, France c Laboratoire d’anatomopathologie, Centre Hospitalier Intercommunal de Cre ´teil, 40 avenue de Verdun, 94010 Cre ´teil Ce ´dex, France article info Article history: Received 3 January 2009 Accepted 11 February 2009 Keywords: Autoantibodies Chronic hepatitis C HCV infection Histology Liver fibrosis abstract Background: Non-organ-specific autoantibodies (NOSAs) are frequently found in the sera of patients with Hepatitis C Virus (HCV) infection. However, no conclusive answers have been produced concerning the clinical relevance of these antibodies. Aim: To determine whether a relationship might exist between the presence of NOSA and the severity of liver disease in chronic hepatitis C. Methods: 186 treatment-naı¨ve chronic hepatitis C patients were studied consecutively for autoanti- bodies. Liver biopsies were analyzed according to the Metavir score. Results: NOSAs were present in 75 patients (40%). Anti-nuclear antibodies were found in 32% of patients (speckled pattern), anti-smooth muscle in 15% without F-actin specificity, anti-mitochondria in 0.5%, and anti-LKM1 in 0.5%, respectively. No liver-cytosol1 or soluble liver antigen antibodies were detected. There was a highly significant correlation between the positivity of NOSA and the degree of inflammation and hepatocellular injury (p = 0.001) and also with the degree of fibrosis (p < 0.0001). The presence of NOSA was associated with higher aspartate aminotransferase, g-glutamyl-transpeptidase, g-globulin and immunoglobulin G levels. By contrast, no differences were observed regarding age, gender, route of infection, duration of disease, HCV genotypes or viral load. Conclusion: NOSAs were associated with the most severe forms of chronic HCV infections. Ó 2009 Elsevier Ltd. All rights reserved. 1. Introduction Hepatitis C Virus infection frequently causes chronic infection leading to liver damage, cirrhosis and hepatocellular carcinoma [1]. Organ-specific and non-specific autoantibodies were first described in autoimmune disorders [2], but many of them may also be found during viral infections. Hepatitis C Virus (HCV) seems to be highly autoimmunogenic because numerous autoantibodies have been detected in HCV-infected patients [3]. Thus the reported prevalence of non-organ-specific autoanti- bodies (NOSAs) ranges from 6% to 21% for anti-nuclear antibodies (ANA), from 12% to 66% for smooth muscle autoantibodies (SMA), and from 0% to 10% for liver kidney microsomal autoantibodies (LKM) [3–7]. Furthermore, patients with chronic hepatitis C may have extrahepatic manifestations or syndromes, some of which are considered to be of immunologic origin, such as: sicca syndrome, autoimmune thyroiditis, mixed cryoglobulinemia, rheumatoid symptoms and glomerulonephritis [8,9]. However, there have been no conclusive findings concerning the clinical relevance of NOSA in chronic hepatitis C, although biochemical evidence of liver disease has been reported in associ- ation with NOSA [4,5,10]. Furthermore, the relationship between their positivity and the severity of liver damage in such patients still remains controversial [4,5,10,11]. The aim of this cohort study was thus to assess the prevalence, type and clinical importance of NOSA in chronic hepatitis C patients and the correlations observed between NOSA positivity and histo- logical characteristics prior to any treatment. 2. Materials and methods 2.1. Study population Between 1999 and 2004, 186 patients with chronic hepatitis C and referred consecutively to the Digestive Diseases Unit at our * Corresponding author. Tel.:þ331 57022224; fax: þ331 57022219. E-mail address: pascale.chretien@chicreteil.fr (P. Chre ´ tien). Contents lists available at ScienceDirect Journal of Autoimmunity journal homepage: www.elsevier.com/locate/jautimm 0896-8411/$ – see front matter Ó 2009 Elsevier Ltd. All rights reserved. doi:10.1016/j.jaut.2009.02.005 Journal of Autoimmunity 32 (2009) 201–205