Current and future treatments of autoimmune hepatitis.
Corticosteroid therapy induces clinical, laboratory and histological improvements in 80% of patients with autoimmune hepatitis. Prednisone, alone or at a lower dose in combination with azathioprine, increases the 20-year life expectancy to 80% and prevents or reduces hepatic fibrosis in 79% of patients. The combination regimen is preferred and treatment should be considered in all patients with active disease. The duration of therapy is finite and the medication should be discontinued after resolution of all manifestations of inflammatory activity, including the histological changes. Relapse after drug withdrawal occurs in 50-79% of patients, and it should be treated with long-term azathioprine (2 mg/kg daily). Salvage therapies for individuals intolerant of or refractory to the conventional regimens include high-dose corticosteroids, with or without high-dose azathioprine, 6-mercaptopurine, mycophenolate mofetil, tacrolimus or ciclosporin. Liver transplantation should be considered in patients with hepatic failure unresponsive to corticosteroid treatment, decompensated cirrhosis with a Model for End-Stage Liver Disease score of at least 15 points, or hepatocellular carcinoma that meets transplantation criteria. Autoimmune hepatitis recurs after transplantation in at least 17% of patients, and it typically improves after adjustments in the immunosuppressive regimen. Future therapies are likely to include mesenchymal stem cell transplantation, adoptive transfer of T regulatory cells, and cytokine manipulation. The emergence of new treatments will require the development of a collaborative network of clinical and basic investigators, as the complexity and specificity of current management problems require solutions that exceed the capabilities of single institutions.
Czaja
Albert J
AJ
Mayo Clinic College of Medicine, Rochester, MN 55905, USA. czaja.albert@mayo.edu
D000305:Adrenal Cortex Hormones / Q000627:therapeutic use*; D001379:Azathioprine / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D004359:Drug Therapy, Combination; D019693:Hepatitis, Autoimmune / Q000188:drug therapy*; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D011241:Prednisone / Q000627:therapeutic use
D000305:Adrenal Cortex Hormones; D007166:Immunosuppressive Agents; D001379:Azathioprine; D011241:Prednisone