AIH, both type 1 and type 2, is also linked to the Human Leukocyte Antigen (HLA) alleles -DR3, -DR4 and -DR7. Early animal models of AIH did not faithfully represent the human disease. We developed a novel mouse model of AIH using the HLA-DR3 transgenic mouse
on the non-obese diabetic (NOD) background (DR3-NOD). Immunization of DR3-NOD mice with a DNA plasmid, coding for human CYP2D6/FTCD fusion protein, leads to a sustained elevation Pexidartinib of alanine aminotransferase (ALT), development of ANA, and chronic immune cell infiltration and parenchymal fibrosis on liver histology. Immunized mice show an enhanced Th1 response and paucity of regulatory T cells (Treg) in the liver and a CYP2D6/FTCD specific T cell response in vitro. This new animal model will help in elucidating further the pathogenesis of AIH and in evaluating the efficacy and safety of immunoreg-ulatory therapeutic interventions in vivo. Disclosures: Isabelle Colle – Advisory Committees
www.selleckchem.com/products/gsk1120212-jtp-74057.html or Review Panels: MSD, Janssen, MSD, Gilead; Grant/Research Support: Bayer; Patent Held/Filed: Trombogenics; Speaking and Teaching: BMS, Janssen The following people have nothing to disclose: Yipeng Wang, Muhammed Yuksel, Junhua Guo, Ningwen Tai, Xiaoyan Xiao, Pascal Lapierre, David Chella, Huiping Yan, Giorgina Mieli Vergani, Diego Vergani, Yun Ma, Li Wen Background: Autoimmune Hepatitis (AIH) is a heterogenous disease with variable onset and progress. Over 85% of patients respond well to steroids and/or thiopurines (AZA). However, in some cases this treatment is not tolerated or sufficient. Alternative treatment options with tacrolimus (tac) and mycophenylate mofetil (MMF) have been described in small series with short follow-up. In this study, we describe long-term follow-up of a cohort of patients with difficult-to-treat AIH with respect to complications, transplantation
and survival. Patients CYTH4 and methods: In a single-centre, retrospective study of 23 patients diagnosed with AIH 1988-2009 and treated with tac and/or MMF, we analysed treatments and potential risk-factors for complications and outcomes, reasons for alternative treatments, rates of liver transplantation and survival. For AIH diagnosis, we used IAIHG criteria. For statistical analyses, Chi-2 and Kruskall-Wallis tests were used. Results: 12/23 patients were female. Median age at diagnosis was 30 years (13-65). Median follow-up time was 10 years (1-24). Initial treatment for all patients was steroids ± AZA. The patients were given tac (n=11) or MMF (n=12) after a median of 3 months (0-9 years), mainly due to intolerance (n=12) or response failure (n=11). This resulted in complete response in 9 patients (39%) and partial response or response with relapse in 11 patients (48%). There was no difference in response between the tac and MMF group (p>0,05).