CoChat
Sign Up
Cited by 167Liver Diseases and ImmunityIgG4-Related and Inflammatory DiseasesDrug-Induced Hepatotoxicity and Protection

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

Open access
Burak, Kelly W, Swain, Mark G, Santodomino-Garzon, Tania, Lee, Samuel S, Urbanski, Stefan J, Aspinall, Alexander I, Coffin, Carla S, Myers, Robert P·2013·Canadian Journal of Gastroenterology
DOI 10.1155/2013/512624PMC PMC3735730
Open this paper in CoChat — free accountOpen PDF

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. 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.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1155/2013/512624

Cites

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • Similar results to B cell depletion in murine models were obtained in a cohort of patients with difficult-to-treat autoimmune hepatitis managed with Rituximab.

    “Similar results were obtained in a cohort of patients with a difficult to treat disease, managed with Rituximab(386, 387), an anti-CD20 medication.”

    From The liver as a central "hub" of the immune system: pathophysiological implications (2025) · cites this paper as [387]

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Cites

No references could be resolved yet.

Research works printed but not linked: 38

  1. Czaja AJ, Freese DK. Diagnosis and treatment of autoimmune hepatitis. Hepatology 2002;36:479-97.
  2. Longhi MS, Ma Y, Mieli-Vergani G, Vergani D. Aetiopathogenesis of autoimmune hepatitis. J Autoimmun 2010;34:7-14.
  3. Manns MP, Czaja AJ, Gorham JD, et al. Diagnosis and management of autoimmune hepatitis. Hepatology 2010;51:2193-213.
  4. Sherman KE, Narkewicz M, Pinto PC. Cyclosporine in the management of corticosteroid-resistant type I autoimmune chronic active hepatitis. J Hepatol 1994;21:1040-7.
  5. Van Thiel DH, Wright H, Carroll P, et al. Tacrolimus: A potential new treatment for autoimmune chronic active hepatitis: Results of an open-label preliminary trial. Am J Gastroenterol 1995;90:771-6.
  6. Pratt DS, Flavin DP, Kaplan MM. The successful treatment of autoimmune hepatitis with 6-mercaptopurine after failure with azathioprine. Gastroenterology 1996;110:271-4.
  7. Kanzler S, Gerken G, Dienes HP, Meyer zum Buschenfelde KH, Lohse AW. Cyclophosphamide as alternative immunosuppressive therapy for autoimmune hepatitis -report of three cases. Z Gastroenterol 1997;35:571-578.
  8. Burak KW, Urbanski SJ, Swain MG. Successful treatment of refractory type 1 autoimmune hepatitis with methotrexate. J Hepatol 1998;29:990-3.
  9. Zandieh I, Krygier D, Wong V, et al. The use of budesonide in the treatment of autoimmune hepatitis in Canada. Can J Gastroenterol 2008;22:388-92.
  10. Richardson PD, James PD, Ryder SD. Mycophenolate mofetil for maintenance of remission in autoimmune hepatitis in patients resistant to or intolerant of azathioprine. J Hepatol 2000;33:371-5.
  11. Devlin SM, Swain MG, Urbanski SJ, Burak KW. Mycophenolate mofetil for the treatment of autoimmune hepatitis in patients refractory to standard therapy. Can J Gastroenterol 2004;18:321-6.
  12. McLaughlin P, White CA, Grillo-Lopez AJ, Maloney DG. Clinical status and optimal use of rituximab for B-cell lymphomas. Oncology (Williston Park) 1998;12:1763-9.
  13. Cohen SB, Emery P, Greenwald MW, et al. Rituximab for rheumatoid arthritis refractory to anti-tumor necrosis factor therapy: esults of a multicenter, randomized, double-blind, placebo- controlled, phase III trial evaluating primary efficacy and safety at twenty-four weeks. Arthritis Rheum 2006;54:2793-806.
  14. Barcellini W, Zanella A. Rituximab therapy for autoimmune haematological diseases. Eur J Intern Med 2011;22:220-9.
  15. Carr DR, Heffernan MP. Innovative uses of rituximab in dermatology. Dermatol Clin 2010;28:547-57.
  16. Myers RP SA, Swain MG, Lee SS, Shaheen AAM, Burak KW. B cell depletion with rituximab in patients with primary biliary cirrhosis refractory to ursodeoxycholic acid. Am J Gastroenterol 2013 (In press).
  17. Breedveld F, Agarwal S, Yin M, et al. Rituximab pharmacokinetics in patients with rheumatoid arthritis: B-cell levels do not correlate with clinical response. J Clin Pharmacol 2007;47:1119-28.
  18. Townsend MJ, Monroe JG, Chan AC. B-cell targeted therapies in human autoimmune diseases: An updated perspective. Immunol Rev 2010;237:264-83.
  19. Liossis SN, Sfikakis PP. Rituximab-induced B cell depletion in autoimmune diseases: Potential effects on T cells. Clin Immunol 2008;127:280-5.
  20. Alvarez F, Berg PA, Bianchi FB, et al. International Autoimmune Hepatitis Group Report: Review of criteria for diagnosis of autoimmune hepatitis. J Hepatol 1999;31:929-38.
  21. Fervenza FC, Cosio FG, Erickson SB, et al. Rituximab treatment of idiopathic membranous nephropathy. Kidney Int 2008;73:117-25.
  22. Batts KP, Ludwig J. Chronic hepatitis. An update on terminology and reporting. Am J Surg Pathol 1995;19:1409-17.
  23. Xu D, Fu J, Jin L, et al. Circulating and liver resident CD4 + CD25 + regulatory T cells actively influence the antiviral immune response and disease progression in patients with hepatitis B. J Immunol 2006;177:739-47.
  24. Valko PO, Bassetti CL, Bloch KE, Held U, Baumann CR. Validation of the fatigue severity scale in a Swiss cohort. Sleep 2008;31:1601-7.
  25. Afif W, Loftus EV Jr, Faubion WA, et al. Clinical utility of measuring infliximab and human anti-chimeric antibody concentrations in patients with inflammatory bowel disease. Am J Gastroenterol 2010;105:1133-9.
  26. Santos ES, Arosemena LR, Raez LE, O'Brien C, Regev A. Successful treatment of autoimmune hepatitis and idiopathic thrombocytopenic purpura with the monoclonal antibody, rituximab: Case report and review of literature. Liver Int 2006;26:625-9.
  27. Evans JT, Shepard MM, Oates JC, Self SE, Reuben A. Rituximab-responsive cryoglobulinemic glomerulonephritis in a patient with autoimmune hepatitis. J Clin Gastroenterol 2008;42:862-3.
  28. Barth E, Clawson J. A case of autoimmune hepatitis treated with rituximab. Case Rep Gastroenterol 2010;4:502-9.
  29. Ferri S, Longhi MS, De Molo C, et al. A multifaceted imbalance of T cells with regulatory function characterizes type 1 autoimmune hepatitis. Hepatology 2010;52:999-1007.
  30. Longhi MS, Hussain MJ, Mitry RR, et al. Functional study of CD4 + CD25 + regulatory T cells in health and autoimmune hepatitis. J Immunol 2006;176:4484-91.
  31. Kessel A, Rosner I, Toubi E. Rituximab: Beyond simple B cell depletion. Clin Rev Allergy Immunol 2008;34:74-9.
  32. Stasi R, Cooper N, Del Poeta G, et al. Analysis of regulatory T-cell changes in patients with idiopathic thrombocytopenic purpura receiving B cell-depleting therapy with rituximab. Blood 2008;112:1147-50.
  33. Sfikakis PP, Souliotis VL, Fragiadaki KG, Moutsopoulos HM, Boletis JN, Theofilopoulos AN. Increased expression of the FoxP3 functional marker of regulatory T cells following B cell depletion with rituximab in patients with lupus nephritis. Clin Immunol 2007;123:66-73.
  34. Feuchtenberger M, Muller S, Roll P, et al. Frequency of regulatory T cells is not affected by transient B cell depletion using anti-CD20 antibodies in rheumatoid arthritis. Open Rheumatol J 2008;2:81-8.
  35. Koyabu M, Uchida K, Miyoshi H, et al. Analysis of regulatory T cells and IgG4-positive plasma cells among patients of IgG4-related sclerosing cholangitis and autoimmune liver diseases. J Gastroenterol 2010;45:732-41.
  36. Tacke F, Zimmermann HW, Berres ML, Trautwein C, Wasmuth HE. Serum chemokine receptor CXCR3 ligands are associated with progression, organ dysfunction and complications of chronic liver diseases. Liver Int 2011;31:840-9.
  37. Nishioji K, Okanoue T, Itoh Y, et al. Increase of chemokine interferon-inducible protein-10 (IP-10) in the serum of patients with autoimmune liver diseases and increase of its mRNA expression in hepatocytes. Clin Exp Immunol 2001;123:271-9.
  38. Nagayama K, Enomoto N, Miyasaka Y, et al. Overexpression of interferon gamma-inducible protein 10 in the liver of patients with type I autoimmune hepatitis identified by suppression subtractive hybridization. Am J Gastroenterol 2001;96:2211-7.

Cited by

Sorted by citations

Authors
Burak, K. W., Swain, M. G., Santodomino-Garzon, T., Lee, S. S., Urbanski, S. J., Aspinall, A. I., Coffin, C. S., & Myers, R. P.
Affiliations
  • University of Calgary (CA)
  • Liver Unit, Division of Gastroenterology and Hepatology, Department of Medicine, University of Calgary, Calgary, Alberta, Canada
Corresponding author
Burak, Kelly W
ORCID
Venue
Canadian Journal of Gastroenterology
Publisher
Wiley
Published
2013
Volume
27
Issue
5
Pages
273-280
ISSN
0835-7900 (ISSN-L)
DOI
10.1155/2013/512624
PMC
PMC3735730
OpenAlex
W116289366
Cited by
167
References
0
Citations by year
2026: 3 · 2025: 13 · 2024: 11 · 2023: 14 · 2022: 13 · 2021: 19 · 2020: 13 · 2019: 17 · 2018: 17 · 2017: 13 · 2016: 8 · 2015: 17 · 2014: 7 · 2013: 2
FWCI
7.04
Type
journal article
Language
en
Update notices
corrigendum (1900-01-01)
Open access
Licence
Locations
  • Canadian Journal of Gastroenterology (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
  • Canadian Institutes of Health Research
  • Genentech
  • Alberta Innovates - Health Solutions
Topics
  • Health Sciences › Medicine › Hepatology › Liver Diseases and Immunity
  • Health Sciences › Medicine › Rheumatology › IgG4-Related and Inflammatory Diseases
  • Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmacology › Drug-Induced Hepatotoxicity and Protection
Keywords
rituximab, autoimmune hepatitis, anti-CD20 monoclonal antibody, B-cell depletion, azathioprine intolerance, IgG, aspartate aminotransferase, regulatory T cells, Foxp3, CXCL10, corticosteroid withdrawal
MeSH terms
Rituximab, Adult, Aged, Aspartate Aminotransferases, Azathioprine, Dose-Response Relationship, Drug, Female, Follow-Up Studies, Humans, Immunoglobulin G, Immunologic Factors, Infusions, Intravenous, Male, Middle Aged, Pilot Projects, Prednisone, Cytokines, Treatment Outcome, Chemokines, Hepatitis, Autoimmune, Antibodies, Monoclonal, Murine-Derived

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review