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


METHODS
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 Corticosteroids could not be withdrawn in the patients treated with mycophenolate mofetil, whereas discontinuation was possible in 7 patients in the comparison group (0% vs. 41%, P = 0.06).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.
Czaja
Albert J
AJ
Division of Gastroenterology and Hepatology, Mayo Clinic College of Medicine, Rochester, MN 55905, USA. czaja.albert@mayo.edu
Carpenter
Herschel A
HA
D000305:Adrenal Cortex Hormones / Q000008:administration & dosage; D000328:Adult; D001219:Aspartate Aminotransferases / Q000097:blood / Q000187:drug effects; D001379:Azathioprine / Q000008:administration & dosage; D001663:Bilirubin / Q000097:blood; D015415:Biomarkers / Q000097:blood; D004305:Dose-Response Relationship, Drug; D005260:Female; D005500:Follow-Up Studies; D019693:Hepatitis, Autoimmune / Q000097:blood / Q000188:drug therapy* / Q000473:pathology; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D009173:Mycophenolic Acid / Q000031:analogs & derivatives* / Q000627:therapeutic use; D011241:Prednisone / Q000008:administration & dosage; D012189:Retrospective Studies; D013997:Time Factors; D016896:Treatment Outcome; D005719:gamma-Globulins / Q000187:drug effects / Q000378:metabolism
D000305:Adrenal Cortex Hormones; D015415:Biomarkers; D007166:Immunosuppressive Agents; D005719:gamma-Globulins; D001219:Aspartate Aminotransferases; D009173:Mycophenolic Acid; D001379:Azathioprine; D001663:Bilirubin; D011241:Prednisone