Mycophenolate Mofetil for Autoimmune Hepatitis

Purpose: Autoimmune hepatitis (AIH) is refractory to standard therapy with prednisone and azathioprine in 20% of patients. For the last decade, investigators have explored alternative immunosuppressant drugs in AIH, including budesonide, cyclosporine, tacrolimus, and mycophenolate mofetil (MMF). Methods: A retrospective analysis was performed in 16 patients with AIH, immune cholangitis, and overlap syndromes between AIH, primary biliary cirrhosis (PBC), and primary sclerosing cholangitis (PSC). MMF was used in lieu of azathioprine on account of patients' intolerance to azathioprine (7 patients), or disease that was refractory to treatment with prednisone and azathioprine (6 patients), or the perceived potency of MMF, compared to azathioprine (3 patients). Results: The median duration of treatment with MMF was 23.1 months (range 1.4–94.9). With initiation of MMF, ALT decreased from a median of 81.5 U/L (range 9–767) to 42.5 U/L (range 16–350) [P= 0.03]. Prednisone dose decreased from a median of 10 mg (range 0–40) to 2.5 mg (range 0–40) [P= 0.01]. Twelve of the 16 patients (75%) had a good response to treatment, including 3 of the 6 patients who had previously been refractory to treatment with prednisone and azathioprine. Five patients (31%) achieved biochemical remission, here defined as a reduction in the ALT from greater than to less than twice normal. This included 2 patients with classical AIH, 2 patients with AIH-PBC overlap syndrome, and one patient with AIH-PSC overlap syndrome. Seven additional patients (44%) were maintained in biochemical remission. Among the 12 responders, 8 patients experienced ALT normalization. Partial prednisone withdrawal was achieved in 6 and complete withdrawal was achieved in 3 patients. Two patients had an incomplete biochemical response to MMF, with liver chemistries remaining greater than twice normal. Two patients experienced treatment failure, with worsening of liver chemistries while treated with MMF. MMF was tolerated well in all but one patient, who discontinued the drug on account of paresthesias. A significant but not clinically relevant reduction in WBC was noted during MMF treatment, from 8.2 thousand/μL (range 2.5–13.2) to 6.0 thousand/μL (range 2.4–13.5) [P= 0.02]. No significant reductions in hematocrit or platelet count occurred. Conclusion: MMF is appropriate for use in patients with AIH and related disorders who are intolerant or unresponsive to azathioprine.