Current and future treatments of autoimmune hepatitis

Abstract

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.

Keywords::

• calcineurin inhibitor
• corticosteroid
• future therapy
• purine antagonist

Financial & competing interests disclosure

The author has no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

No writing assistance was utilized in the production of this manuscript.

Notes

^*Asymptomatic disease may be transient and progressive, and close surveillance is required if treatment is withheld.

Asymptomatic disease commonly becomes symptomatic, and follow-up liver tissue examination and treatment may be necessary.

AST: Aspartate aminotransferase; ULN: Upper limit of normal range.