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Copyright ©2007 Baishideng Publishing Group Co., Limited. All rights reserved.
World J Gastroenterol. Jun 21, 2007; 13(23): 3232-3236
Published online Jun 21, 2007. doi: 10.3748/wjg.v13.i23.3232
Low-dose tacrolimus ameliorates liver inflammation and fibrosis in steroid refractory autoimmune hepatitis
Fin Stolze Larsen, Ben Vainer, Martin Eefsen, Peter Nissen Bjerring, Bent Adel Hansen
Fin Stolze Larsen, Martin Eefsen, Peter Nissen Bjerring, Bent Adel Hansen, Department of Hepatology, Rigshospitalet, University Hospital of Copenhagen, Copenhagen 2100, Denmark
Ben Vainer, Department of Pathology, Rigshospitalet, University Hospital of Copenhagen, Copenhagen 2100, Denmark
Author contributions: All authors contributed equally to the work.
Supported by funding from Rigshospitalet, The Laerdal Foundation for Acute Medicine, Savvaerksejer Jeppe Juhl and wife Ovita Juhls Foundation, The Novo Nordisk Foundation, The AP-Møller Foundation, and an unrestricted grant from Astellas Inc
Correspondence to: Fin Stolze Larsen, MD, PhD, DSc, Department of Hepatology A-2121, Rigshospitalet, Blegdamsvej 3, 2100 Copenhagen, Denmark. stolze@post3.tele.dk
Telephone: +45-35-452357 Fax: +45-35-452913
Received: February 13, 2007
Revised: March 5, 2007
Accepted: March 15, 2007
Published online: June 21, 2007
Abstract

AIM: To determine the efficacy of tacrolimus on clinical status, histopathological status and biochemical markers in patients with steroid refractory autoimmune hepatitis (AIH).

METHODS: Retrospectively, clinical parameters, biochemistry and histology were obtained from patient records.

RESULTS: Nine patients [8 females/1 male, median age 32 (range 16-64) years] were identified to have received tacrolimus for a median duration of 18 (12-37) mo. Before initiation of tacrolimus treatment the patients were maintained on a prednisolone dose of 20 mg daily (range 20-80 mg/d), which was tapered to 7.5 (5-12.5) mg/d (P = 0.004). Alanine aminotransferase and immunoglobulin-G concentrations decreased from 154 (100-475) to 47(22-61) U/L (P = 0.007), and from 16 (10-30.2) to 14.5 (8.4-20) g/L (P = 0.032), respectively. All patients showed improvement of the liver inflammatory activity, as determined by the Ishak score (P = 0.016), while the degree of fibrosis tended to decrease (P = 0.049).

CONCLUSION: The use of low dose tacrolimus can lead to biochemical and histologic improvement of inflammation with no progression of the stage of fibrosis in patients with steroid refractory AIH. Low dose tacrolimus therapy also allows substantial reduction of prednisone dose.

Keywords: Autoimmune hepatitis, Tacrolimus, Prednisone, Azathioprine, Mycophenolate mofetil, Liver failure