| Abstract|| |
Autoimmune hepatitis (AIH) is a chronic inflammatory disease of the liver of unknown cause. Typically, immune suppressive therapy is used initially for treatment, either in the form of steroids or Azathioprime. In a small proportion of patients, steroids resistance or
steroid intolerance develops. When patients are unresponsive to steroids, or develop severe significant side effects to their use, alternative treatments must be used. Mycophenolate mofetil (Cellcept) is a potent immune suppressive medication that is used in a wide variety of autoimmune diseases as well as post solid organ transplantation. Data is emerging to suggest that this medication may be used in selected patients with steroid resistance or steroid intolerance. This data is summarized in this review.
|How to cite this article:|
Abdo AA. Mycophenolate mofetil (CellCept) in patients with autoimmune hepatitis. Saudi J Gastroenterol 2006;12:38
Autoimmune hepatitis (AIH) is a chronic inflammatory disorder of the liver of unknown etiology. Corticosteroids with or without azathioprine have been shown to be effective in inducing and maintaining remission and are currently the standard method of care. Remission occurs in 65% of those affected after 18 months of therapy, and in 80% after three years of therapy. A minority of patients will either be intolerant of, or fail, conventional therapy. A number of other therapies have been studied with mostly disappointing results.
Mycophenolic acid (MMF) is an ester pro-drug of mycophenolic acid which acts as a noncompetitive inhibitor of inosine monophosphate dehydrogenase, the rate-limiting enzyme involved in the de novo syntheses of purines.
For this reason, MMF is used extensively in the setting of solid organ transplantation, other autoimmune conditions such as Crohn disease and for rheumatoid arthritis. The toxicity profile of MMF includes: diarrhea, nausea, vomiting, leucopenia and anemia. The use of MMF in AIH has been the subject of three small studies so far. In the first report successful treatment of one patient with MMF was described. In the second paper, Richardson evaluated the use of MMF in 7 patients with type 1 AIH. Of the seven patients included, three patients were intolerant of azathioprine and had elevated liver enzymes with a liver biopsy showing active inflammation despite prednisone therapy, while four have been on high dose azathiprine without complete normalization of ALT, and had liver biopsies showing active disease.
All patients were treated with MMF 1 g twice daily and were followed for a median of 46 months. Five of the seven patientsentered clinical remission within 3 months of treatment. Thesteroid dose fell from 20 mg per day to 2 mg per day within9 months and the hepatic activity index fell from a medianof 11 to 3 after 7 months of therapy. One patient requireddose reduction because of a fall in the white count. No otheradverse effects were seen.
More recently, Devlin and collegues reported experiencewith 5 patients with classical type 1 AIH who were eitherintolerant of or resistant to steroid therapy. All patientsachieved clinical and biochemical response. There was noliver biopsy follow up in this study except in one patientwho had a significant improvement in inflammation on MMFalone without any steroids.
From the above preliminary data, we feel that MMF is a promising drug in AIH, and should be considered inpatients who are either resistant to, or intolerant of, standard therapy, including steroids and azathioprine. Before MMF isconsidered, every effort should be exhausted to reconfirm thediagnosis, confirm the compliance of the patient to standardtherapy, optimize medical management with medical therapy,and give enough time for standard immunosuppressantmedications to work. In addition, patients should be informedthat MMF therapy for AIH is not a standard approved therapyand all potential side effects should be explained to thepatient in detail.
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Ayman A Abdo
P.O.Box 2925(59) College of Medicine, King Saud University , Riyadh 11461
Source of Support: None, Conflict of Interest: None