title: Clinical and histologic features of Azathioprine-induced hepatotoxicity.
abstract: BACKGROUND
  Hepatoxicity is a relative uncommon complication related with Azathioprine, however most studies were performed in inflammatory bowel diseases patients. The aim of this study is to report the clinical profile of patients with Azathioprine-induced hepatotoxicity.
  
  
  METHODS
  All medical records of patients received Azathioprine from 2010 to 2015 were retrospectively reviewed. Hepatotoxicity was defined as serum alanine aminotransferase (ALT) or aspatate aminotransferase (AST) or total bilirubin >2 times upper limit normal. Other causes of liver diseases were excluded. All subjects were followed until the resolution of liver injury.
  
  
  RESULTS
  Two-hundred and ninety-three patients receiving Azathioprine were retrospectively reviewed. Eight patients (2.7%) were diagnosed with Azathioprine-induced hepatotoxicity. The median age was 45 year with female preponderance. The latency to onset of liver injury ranged from 7 to 236 d, and 4 patients were symptomatic. Median peak levels were ALT 295 U/L, alkaline phosphatase 169 U/L, and total bilirubin 1 mg/dl. According to R-ratio, mixed pattern (50%) was more frequent than cholestatic (37.5%) and hepatocellular pattern (12.5%). Liver biopsies were performed in 2 patients, and showed hepatocellular and canalicular cholestasis with mild portal and peri-portal inflammation. All patients recovered fully with a median time of 41.3 days. Two patients developed prolonged cholestasis >2 months, hence none had liver failure or required liver transplantation.
  
  
  CONCLUSIONS
  Hepatotoxicity is relative uncommon in patients receiving Azathioprine, and predominantly is mixed hepatocellular and cholestatic in nature. Even though all patients recover fully after drug withdrawal, severe cholestasis can occur.
authors.affiliation: a Chulabhorn International College of Medicine , Thammasat University , Pathumthani , Thailand.|b Division of Gastroenterology, Department of Internal Medicine, Faculty of Medicine , Thammasat University , Pathumthani , Thailand.
authors.forename: Sith
authors.initials: S
authors.lastname: Siramolpiwat
authors.affiliation: c Department of Pathology, Faculty of Medicine , Thammasat University , Pathumthani , Thailand.
authors.forename: Dussadee
authors.initials: D
authors.lastname: Sakonlaya
mesh_terms: D000328:Adult; 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 / Q000453:epidemiology* / Q000473:pathology; D002779:Cholestasis / Q000139:chemically induced / Q000453:epidemiology*; D003240:Connective Tissue Diseases / Q000188:drug therapy; D005260:Female; D006402:Hematologic Diseases / Q000188:drug therapy; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects*; D008099:Liver / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies; D013785:Thailand / Q000453:epidemiology
chemical_list: D007166:Immunosuppressive Agents; D000410:Alanine Transaminase; D000469:Alkaline Phosphatase; D001379:Azathioprine; D001663:Bilirubin
keywords: Azathioprine; cholestasis; drug-induced liver injury; hepatotoxicity