mercaptopurine and Cholestasis--Intrahepatic

Azathioprine, a prodrug of 6-mercaptopurine (6-MP), is used in the treatment of inflammatory bowel disease and may be continued during pregnancy. Acute cholestatic liver injury has been reported to occur with azathioprine. We aimed to examine azathioprine related cholestasis effect on pregnancy complications and outcome.. We present a unique case of 6-MP-induced severe intrahepatic cholestasis of pregnancy (ICP) that required meticulous combined therapy including plasma exchange. The symptoms resolved following 6-MP withdrawal. A literature review revealed 11 pregnancies complicated by early-induced severe ICP among women treated with azathioprine or 6-MP.. We recommend weekly bile acid level tests for pregnant women treated with azathioprine or 6-MP, beginning early in the second trimester of pregnancy, and the prompt discontinuation of treatment upon establishment of an ICP diagnosis.

Topics: Azathioprine; Cholestasis, Intrahepatic; Female; Humans; Mercaptopurine; Pregnancy; Pregnancy Complications

Topics: Adult; Chemical and Drug Induced Liver Injury; Cholestasis, Intrahepatic; Diagnosis, Differential; Female; Humans; Mercaptopurine; Pregnancy; Pregnancy Complications

Hepatic dysfunction is a rare presentation of leukemia in children. Because most chemotherapy agents are metabolized by the liver, this complication may have major adverse consequences and effective treatment could be compromised.. The MEDLINE database and current management guidelines from the United States Pediatric Cooperative Cancer Groups were reviewed and analyzed. Data from two institutional cases are described.. Although previous literature is not informative, our experience suggests that children with leukemia and moderate hepatic dysfunction may tolerate aggressive chemotherapy.. Current protocol guidelines for dose modification for liver disease may be overly stringent and modification may be beneficial.

Topics: Adolescent; Antineoplastic Combined Chemotherapy Protocols; Asparaginase; Biopsy; Child, Preschool; Cholestasis, Intrahepatic; Chromosome Deletion; Daunorubicin; Hepatomegaly; Humans; Liver; Liver Function Tests; Male; Mercaptopurine; Methotrexate; Practice Guidelines as Topic; Precursor B-Cell Lymphoblastic Leukemia-Lymphoma; Prednisone; Prognosis; Remission Induction; Thrombocytopenia; Ultrasonography; Vincristine

Treatment with 6-mercaptopurine (6MP) is associated with adverse gastrointestinal (GI) and hepatic effects. Four patients, ages 6.9 +/- 2.6 (mean +/- S.D.) years, with acute lymphocytic leukemia (ALL) on maintenance chemotherapy including 6MP, developed nausea, vomiting, abdominal pain, elevated liver enzymes, and hyperbilirubinemia after 1.4 +/- 1.0 (range 0.5-2) years. Liver biopsy in 1 patient was suggestive of drug-induced intrahepatic cholestatis. Symptoms resolved and liver function returned to normal after discontinuation of 6MP. Pharmacokinetic data of the symptomatic patients were compared with those of 25 ALL patients on the same protocol but without GI symptoms or hepatotoxicity. Levels of 6-thioguanine nucleotides (6-TGN) and the methylated metabolites of 6MP in red blood cells of the patients with hepatotoxicity, were not significantly different when compared to patients without hepatotoxicity, suggesting similar absorption of 6MP in both groups. Time to achieve peak 6MP levels was significantly longer in the symptomatic patients compared to the asymptomatic patients (P = 0.005). Peak levels and standardized concentration versus time curve (AUC) per 1 mg of 6MP per m2 of body surface area were significantly lower in the patients with hepatotoxicity (P = 0.016; P = 0.037, respectively). A significant correlation between peak 6MP levels and standardized AUC (r = 0.729, P < 0.0001) was found. These results suggest accumulation of 6MP and its metabolites in the liver of the patients with GI symptoms, leading to hepatotoxicity.

Topics: Antimetabolites, Antineoplastic; Child; Child, Preschool; Cholestasis, Intrahepatic; Female; Humans; Liver; Male; Mercaptopurine; Precursor Cell Lymphoblastic Leukemia-Lymphoma