Mycophenolate for the treatment of autoimmune hepatitis: prospective assessment of its efficacy and safety for induction and maintenance of remission in a large cohort of treatment-naïve patients.
OBJECTIVE
Standard therapy for autoimmune hepatitis (AIH) is corticosteroids with or without azathioprine. However, 20% of patients do not respond or are intolerant to conventional treatment. Therefore, we evaluated prospectively the efficacy and safety of mycophenolate mofetil (MMF) in inducing and/or maintaining remission in treatment-naïve AIH patients.


METHODS
Fifty-nine treatment-naïve patients with well defined AIH were treated with prednisolone plus 1.5-2g/d of MMF. Patients were candidates for MMF withdrawal after at least 4 years. Treatment outcomes were defined according to the International Autoimmune Hepatitis Group report.


RESULTS
Treatment duration with MMF was 26months (range 3-92). Eighty-eight percent (52/59) of patients responded initially clinically and biochemically (normalization of transaminases and γ-globulins) most of them within 3months. The remaining 7 patients (12%) had partial response. In total, 59.3% (35/59) of patients had complete response (CR) with 37% (22/59) of them having achieved CR off prednisolone, while 28.8% (17/59) had initial CR with relapses. No patient was non-responder. Prednisolone withdrew in 57.6% (34/59) of patients in 8months. The only independent predictor of treatment outcome, was γ-GT (baseline γ-GT, p=0.008 and γ-GT on month 24, p<0.05). Severe side effects leading to MMF discontinuation occurred in only 3.4% (2/59) of patients. Six patients (2 according to protocol and 4 for personal reasons), stopped treatment with MMF, but 3 relapsed.


CONCLUSIONS
MMF seems safe and effective as first-line therapy in inducing and maintaining remission in treatment-naive patients with AIH, having a significant and rapid steroid sparing effect as attested by the fact that so far, 37% (22/59) of AIH patients achieved CR off prednisolone.
Department of Medicine and Research Lab of Internal Medicine, Medical School, University of Thessaly, Larissa, Thessaly, Greece; Institute of Biomedical Research and Technology, Centre for Research and Technology-Thessaly (CE.RE.TE.TH), Larissa, Greece.
Kalliopi
K
Zachou
Department of Medicine and Research Lab of Internal Medicine, Medical School, University of Thessaly, Larissa, Thessaly, Greece.
Nikolaos
N
Gatselis
Department of Medicine and Research Lab of Internal Medicine, Medical School, University of Thessaly, Larissa, Thessaly, Greece.
Georgia
G
Papadamou
Department of Medicine and Research Lab of Internal Medicine, Medical School, University of Thessaly, Larissa, Thessaly, Greece.
Eirini I
EI
Rigopoulou
Department of Medicine and Research Lab of Internal Medicine, Medical School, University of Thessaly, Larissa, Thessaly, Greece; Institute of Biomedical Research and Technology, Centre for Research and Technology-Thessaly (CE.RE.TE.TH), Larissa, Greece. Electronic address: dalekos@med.uth.gr.
George N
GN
Dalekos
D000328:Adult; D000368:Aged; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use; D004359:Drug Therapy, Combination; D005260:Female; D019693:Hepatitis, Autoimmune / Q000097:blood / Q000188:drug therapy* / Q000473:pathology; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D009173:Mycophenolic Acid / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D011239:Prednisolone / Q000627:therapeutic use; D011446:Prospective Studies; D012008:Recurrence; D012074:Remission Induction; D013997:Time Factors; D016896:Treatment Outcome; D005723:gamma-Glutamyltransferase / Q000097:blood
D000893:Anti-Inflammatory Agents; D007166:Immunosuppressive Agents; D011239:Prednisolone; D005723:gamma-Glutamyltransferase; D009173:Mycophenolic Acid