[PubMed] [Google Scholar] 27. groups. Fibrotic groups non-OLT and post TAK-700 Salt (Orteronel Salt) OLT demonstrated significantly higher Th2, Th17 cytokines and lower Th1 cytokines compared to non fibrotic groups. Our results demonstrate that in HCV infection, Abs to ECM Collagen 1, 2, 5 positively correlate with liver fibrosis which is associated with a predominant Th2 and Th17 cytokine profile. Keywords: Autoantibodies, IL-17, Fibrosis, HCV Recurrence Chronic hepatitis C (HCV) is the leading indication for orthotopic liver transplantation (OLT) in the United States, accounting for up to 40C45% of all transplants (1). HCV recurrence in the allograft is universal (2). The natural history of HCV in the native liver is characterized by a slow progression to cirrhosis, end-stage liver disease, and in some cases hepatocellular carcinoma (3). Many factors including but not limited to: age, ethnicity, concurrent alcohol use, duration of infection, inflammatory activity index (HAI) and steatosis (4, 5) account for the variability of progression. HCV following OLT has an accelerated course, with the development of cirrhosis in 20C30% of patients within 5 years (6, 7). In this setting, factors impacting progression of fibrosis include liver donor quality, recipient factors (older age, non-Caucasian race, higher Child-Pugh score prior to transplantation), and systemic immunosuppression (8C10). Liver fibrosis due to different etiologies has been associated with an increased deposition of collagens (Col) and other connective tissue components (11, 12). In particular, HCV infection in the native liver and its recurrence post-transplant has been shown to significantly impact deposition and remodeling of extracellular matrix (ECM) components particularly Col, leading to enhanced fibrosis (13). Further, chronic rejection in the TAK-700 Salt (Orteronel Salt) allograft is initiated by a host-anti-graft-immune response with both antigen-dependent and non-immune (antigen-independent) factors BSG leading to fibroproliferative changes affecting graft function. Inflammation and tissue remodeling promoted by alloimmune mechanisms facilitate the induction of autoimmune responses against self-antigens. Studies in the arena of heart, lung, and kidney transplantation have identified putative mechanisms that contribute to the development of chronic rejection (14, 15). In these instances, an emerging paradigm is that inflammation and associated tissue remodeling attendant to the post-transplant state exposes cryptic self-antigens or their determinants that, along with a favorable cytokine milieu, allows for loss of peripheral tolerance and activation of cell-mediated immunity towards development of de novo immune responses to self antigens (16). Previous studies have shown a higher prevalence of auto-Abs to nuclear, smooth muscle and anti-mitochondrial antigens in patients with chronic HCV infection (17, 18). In addition, the presence of circulating Abs to ECM collagen has been well established in liver disease (19). However the clinical implications of their occurrence, in particular their relation to HCV induced fibrosis of the native and allograft liver and their functional significance in the induction of fibrosis needs better characterization. In this investigation we postulated that chronic HCV infection resulting in liver parenchymal damage and TAK-700 Salt (Orteronel Salt) progressive ECM TAK-700 Salt (Orteronel Salt) remodeling may lead to the induction of an immune response to ECM proteins. This was assessed by determining Abs to ECM collagen (subtypes 1, 2, 4 and 5) and vimentin at various stages of HCV infection in the native liver and in the allograft post OLT. The study group was also examined for the presence of classic autoimmune markers such as anti-nuclear, anti-smooth muscle, anti-mitochondrial Abs, rheumatoid factor and cryoglobulins. In addition, we measured serum levels of pro-inflammatory cytokines (IL-17, IL-6, IL 1, IFN-, IL-4, IL-5, and IL-10) that have previously been implicated in the pathogenesis of liver fibrosis in chronic HCV infection (20, 21). Our results demonstrate that Abs to self antigen ECM collagen positively correlate with stage of liver fibrosis as well as a Th2 and Th17 cytokine milieu both in non OLT and post-OLT HCV patients. PATIENTS AND METHODS HCV patient population Patients followed.