Treatment challenges and investigational opportunities in autoimmune hepatitis

Abstract

New drugs and advances in molecular biology afford opportunities to upgrade the treatment of autoimmune hepatitis. The aims of this study were to define treatment problems, identify possible solutions, and stimulate investigations to improve patient care. A clinical subcommittee of the International Autoimmune Hepatitis Group reviewed current management difficulties and proposed corrective actions. The assessment of new front-line and salvage therapies for adults and children were given top priority. Cyclosporine and mycophenolate mofetil were endorsed as drugs worthy of rigorous study in severe disease, and budesonide was endorsed for study as front-line therapy in mild disease. Diagnostic criteria and treatment regimens for children required codification, and pharmacokinetic studies were encouraged to develop optimal dosing schedules based on therapeutic ranges. Collaborative efforts were proposed to help understand racial, geographical, and genetic factors affecting outcome and to establish definitions and therapies for variant syndromes and graft dysfunction after transplantation. The development of experimental animal models was deemed essential for the study of site-specific molecular interventions, and gene therapy was endorsed as a means of bolstering reparative processes. In conclusion, evolving pharmacological and technical advances promise to improve the treatment of autoimmune hepatitis, and investigations of these advances are timely, feasible, and necessary. (HEPATOLOGY 2005;41:207-215.)

Features associated with treatment failure in type 1 autoimmune hepatitis and predictive value of the model of end-stage liver disease

“…Such therapies have consisted mainly of high-dose corticosteroid regimens, but their lack of efficacy in this study underscores the need for better salvage therapies for autoimmune hepatitis. 58 The performance parameters of the individual components of the MELD score were uniformly lower than those of the composite score except for serum creatinine level (Table 4). A serum creatinine level greater than 1.1 mg/dL at presentation was more specific for treatment failure than the other components (78% versus 61%) and than the composite score (78% versus 68%).…”

Association of HLA-DR14 with the Treatment Response in Japanese Patients with Autoimmune Hepatitis

“…AIH can run a rapid course accompanied by cirrhosis in some cases, particularly in young male patients [11], when they fail to receive a therapeutic intervention [12]. Some patients relapse after treatment, often accompanied by rapid deterioration in the liver histology [13]; they need utmost care for timely and effective treatment.…”

Type I autoimmune hepatitis: clinical course and outcome in an Italian multicentre study

“…Remission of the disease is achieved on treatment in 65-80% of patients. [4][5][6] One study considered the long-term follow-up of patients with maintenance therapy, with azathioprine, as being successful in approximately 80% of patients. 7 A recent paper included 205 white North American patients with type I AIH evaluated between 1975 and 2005 at the Mayo Clinic.…”