mercaptopurine and Cholestasis

Topics: Adrenal Cortex Hormones; Anti-Bacterial Agents; Antipruritics; Azathioprine; Cholangitis, Sclerosing; Cholestasis; Cholestyramine Resin; Humans; Mercaptopurine; Methotrexate; Penicillamine; Ursodeoxycholic Acid; Vitamins

The objective of the study was to define the clinical, biochemical, and histologic features of liver injury from thiopurines.. Azathioprine (Aza) and 6-mercaptopurine (6-MP) can cause liver injury, but no large series exist.. Clinical and laboratory data and 6-month outcomes of patients with thiopurine hepatotoxicity from the Drug-Induced Liver Injury Network Prospective Study were analyzed.. Twenty-two patients were identified, 12 due to Aza and 10 due to 6-MP, with a median age of 55 years; the majority were female (68%). Inflammatory bowel disease was the indication in 55%, and the median thiopurine dose was 150 (range, 25 to 300) mg daily. The median latency to onset was 75 (range, 3 to 2584) days. Injury first arose after a dose escalation in 59% of patients, the median latency after dose increase being 44 (range, 3 to 254) days. At onset, the median alanine aminotransferase level was 210 U/L, alkaline phosphatase was 151 U/L, and bilirubin was 7.4 mg/dL (peak, 13.4 mg/dL). There were no major differences between Aza and 6-MP cases, but anicteric cases typically had nonspecific symptoms and a hepatocellular pattern of enzyme elevations, whereas icteric cases experienced cholestatic hepatitis with modest enzyme elevations in a mixed pattern. One patient with preexisting cirrhosis required liver transplantation; all others resolved clinically. One patient still had moderate alkaline phosphatase elevations 2 years after onset.. Nearly three-quarters of patients with thiopurine-induced liver injury present with self-limited, cholestatic hepatitis, typically within 3 months of starting or a dose increase. The prognosis is favorable except in patients with preexisting cirrhosis.

Topics: Adolescent; Adult; Aged; Alanine Transaminase; Alkaline Phosphatase; Azathioprine; Bilirubin; Chemical and Drug Induced Liver Injury; Child; Cholestasis; Databases, Factual; Female; Humans; Inflammatory Bowel Diseases; Male; Mercaptopurine; Middle Aged; Prospective Studies; Time Factors; Young Adult

Topics: Adrenal Cortex Hormones; Autoimmune Diseases; Azathioprine; Chemical and Drug Induced Liver Injury; Cholestasis; Chronic Disease; Dermatomyositis; Female; Glomerulonephritis; Humans; Lupus Erythematosus, Systemic; Mercaptopurine; Polyarteritis Nodosa; Scleroderma, Systemic; Time Factors

Topics: Autoimmune Diseases; Azathioprine; Child; Cholestasis; Colitis, Ulcerative; Humans; Mercaptopurine; Methylprednisolone; Psychophysiologic Disorders

Topics: Adolescent; Cholestasis; Female; Humans; Lymphatic Diseases; Mercaptopurine

Topics: Adult; Chemical and Drug Induced Liver Injury; Cholestasis; Female; Glomerulonephritis; Humans; Leukemia; Liver Function Tests; Lupus Erythematosus, Systemic; Male; Mercaptopurine; Middle Aged

Topics: Acute Disease; Adolescent; Adrenal Cortex Hormones; Adult; Aged; Azathioprine; Biliary Tract Diseases; Biopsy; Child; Child, Preschool; Cholestasis; Chronic Disease; Diagnosis, Differential; Female; Hepatitis; Hepatitis A; Humans; Infant; Infant, Newborn; Liver Cirrhosis; Liver Cirrhosis, Biliary; Male; Mercaptopurine; Middle Aged; Necrosis