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

Ana Luiza Vilar Guedes, Adriana Ribas Andrade, Vinicius Santos Nunes, Fabiana Roberto Lima, Evandro Sobroza de Mello, Suzane Kioko Ono, Débora Raquel Benedita Terrabuio, Eduardo Luiz Rachid Cançado

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

Keywords


Hepatitis, Autoimmune; Azathioprine; Allopurinol; Azathioprine Metabolism

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DOI: http://dx.doi.org/10.4322/acr.2017.021

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