Histological remission of autoimmune hepatitis after the addition of allopurinol and azathioprine dose reduction

Authors

  • Ana Luiza Vilar Guedes University of São Paulo, School of Medicine, Department of Gastroenterology
  • Adriana Ribas Andrade University of São Paulo, School of Medicine, Department of Gastroenterology
  • Vinicius Santos Nunes University of São Paulo, School of Medicine, Department of Gastroenterology
  • Fabiana Roberto Lima University of São Paulo, School of Medicine, Department of Pathology
  • Evandro Sobroza de Mello University of São Paulo, School of Medicine, Department of Pathology
  • Suzane Kioko Ono University of São Paulo, School of Medicine, Department of Gastroenterology
  • Débora Raquel Benedita Terrabuio University of São Paulo, School of Medicine, Department of Gastroenterology
  • Eduardo Luiz Rachid Cançado University of São Paulo, School of Medicine, Department of Gastroenterology University of São Paulo, Institute of Tropical Medicine of São Paulo

DOI:

https://doi.org/10.4322/acr.2017.021

Keywords:

Hepatitis, Autoimmune, Azathioprine, Allopurinol, Azathioprine Metabolism

Abstract

The standard therapy for some autoimmune diseases consists of a combination of corticosteroids and thiopurines. In non-responders to thiopurine drugs, the measurement of the metabolites of azathioprine, 6-thioguanine, and 6-methylmercaptopurine, can be a useful tool. The measurement has been used during the treatment of inflammatory bowel diseases and, less commonly, in autoimmune hepatitis. Many patients preferentially metabolize thiopurines to 6-methylmercaptopurine (6-MMP), which is potentially hepatotoxic, instead of 6-thioguanine, the active immunosuppressive metabolite. The addition of allopurinol shifts the metabolism of thiopurine towards 6-thioguanine, improving the immunosuppressive effect. We present the case of a 51-year-old female with autoimmune hepatitis who had a biochemical response after azathioprine and prednisone treatment without histological remission, and who preferentially shunted to 6-MMP. After the addition of allopurinol, the patient’s 6-thioguanine levels increased, and she reached histological remission with a reduction of 67% of the original dose of azathioprine. The patient did not develop clinical manifestations as a consequence of her increased immunosuppressive state. We also review the relevant literature related to this issue. In conclusion, the addition of allopurinol to thiopurine seems to be an option for those patients who do not reach histological remission and who have a skewed thiopurine metabolite profile

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Published

2017-06-30

How to Cite

Guedes, A. L. V., Andrade, A. R., Nunes, V. S., Lima, F. R., Mello, E. S. de, Ono, S. K., Terrabuio, D. R. B., & Cançado, E. L. R. (2017). Histological remission of autoimmune hepatitis after the addition of allopurinol and azathioprine dose reduction. Autopsy and Case Reports, 7(2), 35-42. https://doi.org/10.4322/acr.2017.021

Issue

Section

Article / Clinical Case Report