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Methotrexate Treatment of Idiopathic Granulomatous Hepatitis

Tamsin A. Knox, MD, MPH; Marshall M. Kaplan, MD; Jeffrey A. Gelfand, MD; and Sheldon M. Wolff, MD
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From New England Medical Center Hospitals and Tufts University School of Medicine, Boston, Massachusetts. Requests for Reprints: Tamsin A. Knox, MD, MPH, Division of Gastroenterology, New England Medical Center, Box 103, 750 Washington Street, Boston, MA 02111. Acknowledgments: The authors are indebted to Dr. Wolff, who spent many years caring for these patients, encouraged this trial of methotrexate, and died before this manuscript was completed and submitted.

Copyright ©2004 by the American College of Physicians

Ann Intern Med. 1995;122(8):592-595. doi:10.7326/0003-4819-122-8-199504150-00006
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Objective: To test the efficacy and safety of low-dose oral pulse methotrexate therapy in patients with idiopathic granulomatous hepatitis who had complications of, did not respond to, or refused glucocorticoid therapy.

Design: Prospective case study.

Setting: Academic medical center hospital.

Patients: Seven patients with biopsy-proven, idiopathic granulomatous hepatitis who could not tolerate or were unresponsive to glucocorticoid therapy.

Intervention: Low-dose oral pulse methotrexate, 15 mg/wk.

Measurements: Temperature, symptoms, dose of concurrent glucocorticoids, biochemical tests of liver function, side effects of methotrexate, and assessment of liver biopsy specimens.

Results: All six febrile patients became afebrile within 3 months of starting methotrexate. Fatigue and anorexia improved in all patients. Glucocorticoid therapy was successfully discontinued within 6 months of starting methotrexate in four patients receiving prednisone at entry. Liver biopsy specimens were obtained again after methotrexate therapy and showed absence of granulomas in four of four patients. The minimum effective dose of methotrexate was 0.20 mg/kg body weight per week. No serious adverse effects and no failures to respond to methotrexate therapy were noted in this group of patients. In three patients, methotrexate therapy has been successfully tapered without signs or symptoms of recurrent disease.

Conclusions: Low-dose oral pulse methotrexate was effective in treating patients with granulomatous hepatitis.


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Figure 1.
Liver biopsy specimen from patient 3 before and after methotrexate therapy. Top.Bottom.

Biopsy specimen before methotrexate therapy. Multiple, noncaseating granulomas are shown. (Hematoxylin and eosin; original magnification, × 175.) Biopsy specimen after 1 year of methotrexate therapy. No granuloma, fibrosis, or increase in inflammation is present. (Hematoxylin and eosin; original magnification, × 175.).

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