title: Azathioprine and 6-Mercaptopurine-induced Liver Injury: Clinical Features and Outcomes.
abstract: 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.
authors.affiliation: *Liver Disease Research Branch, Division of Digestive Diseases and Nutrition, National Institutes of Health, Bethesda, MD †The Faculty of Medicine, University of Iceland ‡National University Hospital of Iceland, Reykjavik, Iceland §Duke Clinical Research Institute, Durham, NC ∥Laboratory of Pathology, National Cancer Institute, National Institutes of Health ¶Indiana University School of Medicine, Indianapolis, IN #University of North Carolina, Chapel Hill, NC.
authors.forename: Einar S
authors.initials: ES
authors.lastname: Björnsson
authors.forename: Jiezhun
authors.initials: J
authors.lastname: Gu
authors.forename: David E
authors.initials: DE
authors.lastname: Kleiner
authors.forename: Naga
authors.initials: N
authors.lastname: Chalasani
authors.forename: Paul H
authors.initials: PH
authors.lastname: Hayashi
authors.forename: Jay H
authors.initials: JH
authors.lastname: Hoofnagle
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000410:Alanine Transaminase / Q000097:blood; D000469:Alkaline Phosphatase / Q000097:blood; D001379:Azathioprine / Q000008:administration & dosage / Q000009:adverse effects*; D001663:Bilirubin / Q000097:blood; D056486:Chemical and Drug Induced Liver Injury / Q000097:blood* / Q000209:etiology; D002648:Child; D002779:Cholestasis / Q000139:chemically induced*; D016208:Databases, Factual; D005260:Female; D006801:Humans; D015212:Inflammatory Bowel Diseases / Q000188:drug therapy; D008297:Male; D015122:Mercaptopurine / Q000008:administration & dosage / Q000009:adverse effects*; D008875:Middle Aged; D011446:Prospective Studies; D013997:Time Factors; D055815:Young Adult
chemical_list: D015122:Mercaptopurine; D000410:Alanine Transaminase; D000469:Alkaline Phosphatase; D001379:Azathioprine; D001663:Bilirubin