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Canadian Journal of Gastroenterology
Volume 27, Issue 5, Pages 273-280
Original Article

Rituximab for the Treatment of Patients with Autoimmune Hepatitis Who are Refractory or Intolerant to Standard Therapy

Kelly W Burak,1 Mark G Swain,1 Tania Santodomino-Garzon,1 Samuel S Lee,1 Stefan J Urbanski,2 Alexander I Aspinall,1 Carla S Coffin,1 and Robert P Myers1

1Liver Unit, Division of Gastroenterology and Hepatology, Department of Medicine, University of Calgary, Calgary, Alberta, Canada
2Department of Pathology, University of Calgary, Calgary, Alberta, Canada

Received 2 December 2012; Accepted 9 December 2012

Copyright © 2013 Hindawi Publishing Corporation. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


BACKGROUND: Although most patients with autoimmune hepatitis (AIH) respond to treatment with prednisone and/or azathioprine, some patients are intolerant or refractory to standard therapy. Rituximab is an anti-CD20 monoclonal antibody that depletes B cells and has demonstrated efficacy in other autoimmune conditions.

AIMS: To evaluate the safety and efficacy of rituximab in patients with refractory AIH in an open-label, single-centre pilot study.

METHODS: Six patients with definite, biopsy-proven AIH who failed prednisone and azathioprine treatment received two infusions of rituximab 1000 mg two weeks apart and were followed for 72 weeks.

RESULTS: Rituximab was well tolerated with no serious adverse events. By week 24, mean (± SD) aspartate aminotransferase (AST) levels had significantly improved (90.0±23.3 U/L versus 31.3±4.2 U/L; P=0.03) and mean immunoglobulin G levels had fallen (16.4±2.0 g/L versus 11.5±1.1 g/L; P=0.056). The prednisone dose was weaned in three of four subjects, with one subject flaring after steroid withdrawal. Inflammation grade improved in all four subjects who underwent repeat liver biopsy at week 48. Regulatory T cell levels examined by FoxP3 immunohistochemistry paralleled inflammatory activity and did not increase on follow-up biopsies. There was no significant change in serum chemokine or cytokine levels from baseline to week 24 (n=5), although interferon-gamma-induced protein 10 levels improved in three of five subjects.

CONCLUSIONS: Rituximab was safe, well tolerated and resulted in biochemical improvement in subjects with refractory AIH. These results support further investigation of rituximab as a treatment for AIH.