Mercaptopurine rescue after azathioprine‐induced liver injury in inflammatory bowel disease

Abstract

SUMMARYBackground Azathioprine (AZA) liver toxicity arises in approximately 3% of inflammatory bowel disease patients and may result in treatment discontinuation.

Early prediction of thiopurine‐induced hepatotoxicity in inflammatory bowel disease

“…Our findings seem not to be in line with the results of previous studies reporting tolerance of MP in patients who have failed AZA treatment . An important aspect of AZA metabolism is the possible depletion of glutathione in hepatocytes, when AZA is converted to MP and methylnitroimidazole by glutathione S‐transferase in the liver .…”

“…This might explain that for some patients (40–90%) who failed AZA treatment due to imidazole‐related or dose‐dependent intolerance, MP can be a safe and effective alternative. Patients with early AZA intolerance, including gastrointestinal complaints and hepatotoxicity, should therefore be given a trial of MP before thiopurine therapy is discarded …”

“…14 Our findings seem not to be in line with the results of previous studies reporting tolerance of MP in patients who have failed AZA treatment. [22][23][24] An important aspect of AZA metabolism is the possible depletion of glutathione in hepatocytes, when AZA is converted to MP and methylnitroimidazole by glutathione S-transferase in the liver. 25 In addition, methylnitroimidazole may cause AZA intolerance in a considerable group of patients, including nausea and vomiting, flu-like illness, myalgia, arthralgia, headaches and diarrhoea.…”

“…Patients with early AZA intolerance, including gastrointestinal complaints and hepatotoxicity, should therefore be given a trial of MP before thiopurine therapy is discarded. 7,[22][23][24]26 Thiopurine metabolism is complex and unpredictable due to the involvement of the great variety of metabolic enzymes. 3 The individual genetic variants in genes encoding the metabolic enzymes that have been investigated, cannot predict the majority of the adverse reactions.…”

Editorial: can we get more clinical benefit from thiopurine metabolite testing?

“…Hepatoxicity was observed more frequently with mercaptopurine treatment. This is unusual, given several reports that most patients with azathioprine‐induced liver toxicity can be successfully switched to mercaptopurine …”