CASE REPORT Azathioprine Induced Liver Injury: A Case Report Narendra S. Choudhary • Sachin Gupta • Yogesh K. Chawla • Ajay Duseja • Radha K. Dhiman • Ashim Das Received: 9 October 2011 / Accepted: 5 January 2012 / Published online: 22 April 2012 Ó Springer Science+Business Media, LLC 2012 Keywords Azathioprine Á Liver injury Á Cholestasis Introduction Azathioprine is used commonly in clinical practice for various autoimmune diseases. It is known to cause multiple adverse effects including hepatotoxicity. Azathioprine- induced liver injury is rare in clinical practice but can manifest in several ways. Here, we report a case of azathioprine-induced hepato- toxicity manifesting as cholestatic jaundice. Case Report A 61-year-old obese male (BMI 32 kg/m 2 ) had vesicular lesions over arms and abdomen and was diagnosed as subacute spongiotic dermatitis. He was started on azathi- oprine at a dose of 50 mg twice a day. He developed jaundice after 16 days of starting azathioprine therapy. Liver function test revealed cholestatic type of liver injury (Table 1). His hemogram and renal function tests were normal. Work-up for hepatotrophic viruses, i.e. serologies for A, B, C and E as well as HBV DNA and HCV RNA, were negative. Markers for autoimmune liver disease were negative. Liver biopsy revealed moderate canalicular and intrahepatocytic cholestasis with maintained lobular archi- tecture, portal tracts and bile ducts (Fig. 1). According to RUCAM criteria (scoring system used for the diagnosis of drug-induced liver injury), the score in this patient was 9, which indicates highly probable/definite drug-induced liver injury. The patient was managed conservatively with cessation of azathioprine and supplemented with ursodeoxycolic acid in a dose of 600 mg per day. He showed significant improvement clinically as well as biochemically. Discussion Azathioprine is a commonly used immunosuppressive drug, mainly for patients of inflammatory bowel disease. Drug-induced liver injuries (DILI) are difficult to diagnose; RUCAM criteria are widely used for this purpose [1]. Recently, DILI has been defined as ALT C 5 times ele- vation above upper limit of normal (ULN) or ALP eleva- tion C2 times ULN or ALT C 3 ULN with simultaneous elevation of bilirubin to C2 ULN. Clinical types of liver injury are defined using an R value (R = ALT upper limit of normal/ALP upper limit of normal); R C 5 signifies hepatocellular injury while R B 2 signifies cholestatic injury; R values in between 2 and 5 are suggestive of a mixed type of liver injury [2]. Multiple mechanisms may be related to azathioprine-related hepatotoxicity; these include genetic predisposition (HLA association), elevated thiopurine methyl transferase activity or oxidation of azathioprine by xanthine oxidase (generation of reac- tive oxygen species) [3]. Hepatotoxic manifestations of azathioprine include destructive cholangitis, cholestatic N. S. Choudhary Á S. Gupta Á Y. K. Chawla (&) Á A. Duseja Á R. K. Dhiman Department of Hepatology, Post Graduate Institute of Medical Education and Research, Chandigarh, India e-mail: chawlayogesh@yahoo.co.in A. Das Department of Histopathology, Post Graduate Institute of Medical Education and Research, Chandigarh, India 123 Dig Dis Sci (2012) 57:1717–1718 DOI 10.1007/s10620-012-2056-0