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About 10% of patients with autoimmune hepatitis are nonresponsive or intolerant to thiopurine therapy. A skewed metabolism, leading to the preferential generation of toxic thiopurine metabolites instead of the metabolic active 6-tioguanine nucleotides, may explain this unfavorable outcome. Dr de Boer and colleages examined co-administration of allopurinol to low-dose thiopurine therapy may effectively revert this deviant metabolism, as has been shown in inflammatory bowel disease. The team described the effect of adding allopurinol to low-dose thiopurine therapy in patients with AIH with intolerance or nonresponse to normal thiopurine dosages due to a skewed metabolism. The researchers examined the clinical efficacy and tolerability of allopurinol–thiopurine combination therapy with allopurinol 100 mg and low-dose thiopurine in eight AIH patients with a skewed thiopurine metabolism. Patients were switched because of dose-limiting intolerance, nonresponse or loss of response to conventional thiopurine treatment.  | | All 8 patients showed biochemical improvement with a reduction | | Alimentary Pharmacology & Therapeutics |
The research team reported that all 8 patients showed biochemical improvement with a reduction in median alanine aminotransferase levels of 62 U/L at start to 35 U/L at 1 month. This clinical benefit was sustained in 7 patients. The doctors found that allopurinol–thiopurine combination therapy effectively bypassed thiopurine side effects in 4 of 5 patients. Median 6-tioguanine nucleotides levels increased from 100 to 200 pmol/8 × 108 red blood cells at 3 months. The researchers observed that median 6-MMP levels decreased in all patients from 6090 to 175 pmol/8 × 108 RBC. Dr de Boer's team concluded, "Allopurinol safely and effectively optimises thiopurine therapy in patients with autoimmune hepatitis with intolerance and/or nonresponse due to an unfavorable thiopurine metabolism."
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