Mercaptopurine and azathioprine are effective in the treatment of inflammatory bowel disease (IBD).
However, drug-induced hepatotoxicity has been reported in 10% to 15% of pediatric patients.
|90% of all patients had no hepatotoxicity|
|The American Journal of Gastroenterology|
Hepatotoxicity has been associated with the mercaptopurine metabolite methylmercaptopurine ribonucleotide at levels over 5,700 pmol/ 8 × 108 red blood cells (RBC).
Dr Omid Shaye and colleagues from California, USA assessed the prevalence of mercaptopurine/azathioprine hepatotoxicity and its correlation with serum methylmercaptopurine ribonucleotide levels in 173 adult IBD patients.
The team measured aminotransferases, bilirubin, and mercaptopurine metabolite levels in patients treated from 2002 to 2003.
Hepatotoxicity was defined as aspartate aminotransferase and/or alanine aminotranferease 2 times the upper limit of normal or cholestasis.
The researchers found that 8 patients met criteria for a diagnosis of mercaptopurine/azathioprine-induced hepatotoxicity.
The mean methylmercaptopurine ribonucleotide level in these 8 patients was 10,537 pmol/8 × 108 RBC versus 3,452 pmol/8 × 108 RBC in the nonhepatotoxic group.
The team found that the risk of hepatotoxicity above the third quartile was 5 times that below the third quartile.
However, the researchers observed that nearly 90% of all patients with methylmercaptopurine ribonucleotide over 5,300 pmol/8 x 108 RBC had no hepatotoxicity.
Almost 40% of subjects with hepatotoxicity had methylmercaptopurine ribonucleotide levels below this cutoff.
Dr Shaye's team concluded,"Mercaptopurine/azathioprine-induced hepatotoxicity is uncommon in the adult population."
"However, hepatotoxicity is associated with higher mean methylmercaptopurine ribonucleotide levels."
"The sensitivity and specificity of methylmercaptopurine ribonucleotide for drug-induced hepatotoxicity was poor."
"Monitoring liver tests in patients on mercaptopurine/azathioprine is suggested."
"Dose reduction or cessation of mercaptopurine/azathioprine, even with high methylmercaptopurine ribonucleotide levels, should be reserved for patients with elevated aminotransferases."