Empiric therapy of autoimmune hepatitis with mycophenolate mofetil: comparison with conventional treatment for refractory disease

J Clin Gastroenterol. 2005 Oct;39(9):819-25. doi: 10.1097/01.mcg.0000177260.72692.e8.

Abstract

Goal: To assess the outcomes of empiric therapy with mycophenolate mofetil in patients with autoimmune hepatitis.

Background: Mycophenolate mofetil is a purine antagonist that selectively inhibits immunocyte proliferation, and its empiric use in autoimmune hepatitis has been stimulated by small clinical experiences.

Study: Eight patients received mycophenolate mofetil (0.5-3 g daily) for 19 +/- 7 months as frontline therapy or after adverse responses to conventional corticosteroid treatment. Seventeen patients who had been treated with high-dose corticosteroid regimens after treatment failure constituted a historical comparison population.

Results: Five of the 8 patients receiving mycophenolate mofetil and all 17 patients who had been treated with the conventional corticosteroid regimens for treatment failure responded to therapy. The frequency of response (62% vs. 100%, P = 0.02) was lower during longer intervals of treatment (19 +/- 7 months vs. 6 +/- 1 months, P = 0.02) in the patients receiving mycophenolate mofetil. None receiving mycophenolate mofetil resolved their laboratory abnormalities, whereas 6 patients in the comparison group improved to normal tests (0% vs. 35%, P = 0.1). Histologic resolution did not occur in 4 patients sampled during treatment, and successive specimens in 2 patients showed progressive fibrosis. Corticosteroids could not be withdrawn in the patients treated with mycophenolate mofetil, whereas discontinuation was possible in 7 patients in the comparison group (0% vs. 41%, P = 0.06).

Conclusions: Mycophenolate mofetil did not induce laboratory resolution, prevent progressive fibrosis, or allow corticosteroid withdrawal. Clinical trials are needed to evaluate its role and target population.

Publication types

  • Comparative Study

MeSH terms

  • Adrenal Cortex Hormones / administration & dosage
  • Adult
  • Aspartate Aminotransferases / blood
  • Aspartate Aminotransferases / drug effects
  • Azathioprine / administration & dosage
  • Bilirubin / blood
  • Biomarkers / blood
  • Dose-Response Relationship, Drug
  • Female
  • Follow-Up Studies
  • Hepatitis, Autoimmune / blood
  • Hepatitis, Autoimmune / drug therapy*
  • Hepatitis, Autoimmune / pathology
  • Humans
  • Immunosuppressive Agents / therapeutic use*
  • Male
  • Middle Aged
  • Mycophenolic Acid / analogs & derivatives*
  • Mycophenolic Acid / therapeutic use
  • Prednisone / administration & dosage
  • Retrospective Studies
  • Time Factors
  • Treatment Outcome
  • gamma-Globulins / drug effects
  • gamma-Globulins / metabolism

Substances

  • Adrenal Cortex Hormones
  • Biomarkers
  • Immunosuppressive Agents
  • gamma-Globulins
  • Aspartate Aminotransferases
  • Mycophenolic Acid
  • Azathioprine
  • Bilirubin
  • Prednisone