title: Rituximab for the treatment of patients with autoimmune hepatitis who are refractory or intolerant to standard therapy.
abstract: 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.
  
  
  OBJECTIVE
  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.
authors.affiliation: Liver Unit, Division of Gastroenterologyand Hepatology, Department of Medicine, University of Calgary, Calgary, Alberta, Canada. kwburak@ucalgary.ca
authors.forename: Kelly W
authors.initials: KW
authors.lastname: Burak
authors.forename: Mark G
authors.initials: MG
authors.lastname: Swain
authors.forename: Tania
authors.initials: T
authors.lastname: Santodomingo-Garzon
authors.forename: Tania
authors.initials: T
authors.lastname: Santodomino-Garzon
authors.forename: Samuel S
authors.initials: SS
authors.lastname: Lee
authors.forename: Stefan J
authors.initials: SJ
authors.lastname: Urbanski
authors.forename: Alexander I
authors.initials: AI
authors.lastname: Aspinall
authors.forename: Carla S
authors.initials: CS
authors.lastname: Coffin
authors.forename: Robert P
authors.initials: RP
authors.lastname: Myers
mesh_terms: D000328:Adult; D000368:Aged; D058846:Antibodies, Monoclonal, Murine-Derived / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D001219:Aspartate Aminotransferases / Q000378:metabolism; D001379:Azathioprine / Q000627:therapeutic use; D018925:Chemokines / Q000097:blood; D016207:Cytokines / Q000276:immunology; D004305:Dose-Response Relationship, Drug; D005260:Female; D005500:Follow-Up Studies; D019693:Hepatitis, Autoimmune / Q000188:drug therapy*; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood; D007155:Immunologic Factors / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D007262:Infusions, Intravenous; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D011241:Prednisone / Q000008:administration & dosage / Q000627:therapeutic use; D000069283:Rituximab; D016896:Treatment Outcome
chemical_list: D058846:Antibodies, Monoclonal, Murine-Derived; D018925:Chemokines; D016207:Cytokines; D007074:Immunoglobulin G; D007155:Immunologic Factors; D000069283:Rituximab; D001219:Aspartate Aminotransferases; D001379:Azathioprine; D011241:Prednisone