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Sustained Biochemical and Histologic Remission of Primary Biliary Cirrhosis in Response to Medical Treatment

Marshall M. Kaplan, MD; Ronald A. DeLellis, MD; and Hubert J. Wolfe, MD
[+] Article and Author Information

From New England Medical Center, Tufts University School of Medicine, and the Tupper Research Institute, Boston, Massachusetts. Acknowledgment: The authors thank Ms. Jane Bankoff Popkin for assistance with manuscript preparation. Grant Support: In part by General Clinical Research Center Grant RR 00054 from the National Institutes of Health National Center for Research Resources and by GRASP Center grant P30 DK34928 from the National Institute of Diabetes and Digestive and Kidney Diseases. Requests for Reprints: Marshall M. Kaplan, MD, Gastroenterology Division, Box 233, New England Medical Center, 750 Washington Street, Boston, MA 02111. Current Author Addresses: Drs. Kaplan, DeLellis, and Wolfe: Gastroenterology Division, Box 233, New England Medical Center, 750 Washington Street, Boston, MA 02111.


Copyright ©2004 by the American College of Physicians


Ann Intern Med. 1997;126(9):682-688. doi:10.7326/0003-4819-126-9-199705010-00002
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Background: Treatment of primary biliary cirrhosis with ursodiol or colchicine may stabilize the disease or slow its rate of progression, but no reports of spontaneous or treatment-related remission have been published.

Objective: To determine whether primary biliary cirrhosis fully responds to low-dose oral methotrexate therapy.

Design: Prospective case study with at least 6 years of observation.

Setting: Academic medical center.

Patients: 5 of 19 patients with biopsy-proven precirrhotic primary biliary cirrhosis who had been ill for at least 1 year. Three of the 5 had not responded to colchicine or had responded only partially.

Intervention: Oral methotrexate, 15 mg/wk in divided doses.

Measurements: Symptoms, biochemical tests of liver function, and percutaneous liver biopsies. The latter were done at baseline, 1 to 2 years after initiation of methotrexate therapy, and then every 2 to 3 years during methotrexate therapy.

Results: All 5 patients completely responded to medical treatment. Results of biochemical tests of liver function became normal, symptoms remitted, and serial liver biopsy specimens showed progressive histologic improvement. Biopsy specimens obtained after 5 to 12 years of treatment showed few signs of primary biliary cirrhosis and, in 3 patients, were close to normal. Five of the other 14 patients have responded biochemically and have shown histologic improvement; the other 9 have not responded to methotrexate therapy, have discontinued therapy, or have been lost to follow-up.

Conclusion: In some patients, primary biliary cirrhosis may remit in response to methotrexate alone or in combination with colchicine or ursodiol.

Figures

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Figure 1.
Liver biopsy specimens before and after methotrexate therapy for primary biliary cirrhosis.arrow

A. Patient 1 before colchicine therapy, 0.6 mg twice daily. Several portal triads are greatly enlarged, scarred, and infiltrated with mononuclear inflammatory cells. Bridging of adjacent portal triads is seen. Degenerating bile ducts are at the center of the inflammatory infiltrate. Specimen is typical of stage II to III disease. (Masson trichrome; original magnification, x94.) B. Patient 1 after 11 years of treatment: 5 years with colchicine alone; 3 years with colchicine, 0.6 mg twice daily, and methotrexate, 15 mg/wk; and 3 years with colchicine, methotrexate, and ursodeoxycholic acid. Normal parenchyma, minimally scarred portal triads, and no inflammation or any feature of disease are shown. (Masson trichrome; original magnification, x60.) C. Patient 2 before treatment with methotrexate, 15 mg/wk. Portal triads are greatly expanded and infiltrated with mononuclear inflammatory cells. Florid bile duct lesion is visible ( ). The bridging of enlarged portal triads is a finding consistent with stage III disease. (Hematoxylin and eosin; original magnification, x60.) D. Patient 2 after 4 years of treatment with methotrexate, 15 mg/wk. Normal parenchyma; inflammation confined to the portal triads (some of which are moderately enlarged). Normal bile ducts; no bridging of adjacent portal triads. (Masson trichrome; original magnification, x60.) E. Patient 3 five years after diagnosis of disease and 1 year after treatment with colchicine, 0.6 mg twice daily. Portal triads are greatly enlarged, somewhat edematous, and infiltrated with mononuclear inflammatory cells. Bridging of adjacent triads and early nodule formation are evident. Specimen shows stage III to IV disease. (Masson trichrome; original magnification, x94.) F. Patient 3 after 6 years of methotrexate therapy. Specimen is normal except for portal triads that are minimally enlarged and infiltrated with mononuclear cells. No features of disease are seen. (Masson trichrome; original magnification, x94.).

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