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.
Highlights
The current therapy of autoimmune hepatitis (AIH) consists of corticosteroids as monotherapy or, more commonly, in combination with azathioprine (AZA), and both have similar response rates
The patient provided written informed consent to the use of allopurinol and to have this information published. This patient had a definite diagnosis of AIH according to both the classical and the simplified criteria of IAIHG, with a final score of 20 and 7 before treatment, respectively.[11,12]
The first goal in the treatment of AIH is to reach the complete biochemical response, which means the normalization of aminotransferase levels, regardless of the period of time that it takes for the patient to achieve this result
Summary
The current therapy of autoimmune hepatitis (AIH) consists of corticosteroids (prednisone [PD]/prednisolone) as monotherapy or, more commonly, in combination with azathioprine (AZA), and both have similar response rates. In the combined therapeutic regimen, the starting dose of PD is usually 30 mg/day together with 50 mg/day AZA This regimen has fewer side effects when compared with PD alone (10% vs 44%).[1] During the treatment, the dose of corticosteroid is continuously tapered, whereas the dose of AZA is increased, with the final doses varying from 5 mg to 15 mg, and a University of São Paulo, School of Medicine, Department of Gastroenterology. There are few reported cases in which this approach was performed in AIH This is the report of a 51-year-old female with AIH, with only a biochemical response with PD and AZA, who had never achieved histological remission. Relevant publications with a similar approach in AIH are discussed, but it is important to note that this is the first case reported in AIH with histological remission proven by liver biopsy
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
