title: Cutting edge issues in autoimmune hepatitis.
abstract: Autoimmune hepatitis (AIH) is a severe liver disease affecting all age groups worldwide. Novel basic and clinical aspects of AIH, addressed at a Monothematic Conference in London in September 2015, are highlighted in this review. The diagnosis of AIH relies upon detection of characteristic autoantibodies, hypergammaglobulinemia, and interface hepatitis on liver histology. The International Autoimmune Hepatitis Group (IAIHG) has devised diagnostic scoring systems to help in comparative studies and clinical practice. AIH arises in a genetically predisposed host, when yet unknown triggers - such an encounter with a pathogen - lead to a T cell-mediated immune response targeting liver autoantigens. This immune response is inadequately controlled because regulatory mechanisms are impaired. The mainstay of treatment for AIH is immunosuppression, which should be instituted as soon as the diagnosis is made. Standard treatment regimens include relatively high doses of predniso(lo)ne, which are tapered gradually as azathioprine is introduced. Recent guidelines have described newer treatment regimens and have tightened the goal of therapy to complete normalization of biochemical, serological and histological parameters. Mycophenolate mofetil, calcineurin inhibitors, mTOR inhibitors and biological agents are potential salvage therapies, but should be reserved for selected non-responsive patients and administered only in experienced centers. Liver transplantation is a life-saving option for those patients who progress to end-stage liver disease. Further dissection of cellular and molecular pathways involved in AIH pathogenesis is likely to lead to the discovery of novel, tailored and better tolerated therapies.
authors: Institute of Liver Studies, King's College Hospital, London, UK.
authors: Rodrigo
authors: R
authors: Liberal
authors: Department of Medicine, Dartmouth College, Hanover, NH, USA; Department of Medicine, University of Vermont, Burlington, VT, USA.
authors: Edward L
authors: EL
authors: Krawitt
authors: Departments of Medicine and Surgery, Baylor College of Medicine, Baylor-St Luke's Medical Center, Houston, TX, USA.
authors: John M
authors: JM
authors: Vierling
authors: Hannover Medical School, Hannover, Germany.
authors: Michael P
authors: MP
authors: Manns
authors: Institute of Liver Studies, King's College Hospital, London, UK; Paediatric Liver, GI & Nutrition Centre, King's College Hospital, London, UK.
authors: Giorgina
authors: G
authors: Mieli-Vergani
authors: Institute of Liver Studies, King's College Hospital, London, UK. Electronic address: diego.vergani@kcl.ac.uk.
authors: Diego
authors: D
authors: Vergani
mesh_terms: D001379:Azathioprine / Q000627:therapeutic use; D004359:Drug Therapy, Combination; D020022:Genetic Predisposition to Disease / Q000235:genetics; D006680:HLA Antigens / Q000235:genetics; D019693:Hepatitis, Autoimmune / Q000175:diagnosis* / Q000188:drug therapy* / Q000235:genetics; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D008099:Liver / Q000187:drug effects* / Q000276:immunology / Q000601:surgery; D016031:Liver Transplantation; D011239:Prednisolone / Q000627:therapeutic use
chemical_list: D006680:HLA Antigens; D007166:Immunosuppressive Agents; D011239:Prednisolone; D001379:Azathioprine
keywords: Autoimmune hepatitis; Immunosuppression; International Autoimmune Hepatitis Group; Pathogenesis