Severe azathioprine-induced liver injury 22 months after initiation of treatment

Abstract

Drug-induced liver injury (DILI) is the leading cause of acute liver failure in high-income countries. Acute cholestasis is one of the most common forms of hepatotoxicity induced by azathioprine. It usually begins during the first year of treatment, with most cases reported during the first month. We describe an uncommon case of DILI that occurred after 22 months of drug administration. A woman in her 50s was hospitalised because of jaundice and asthenia. She had been treated with azathioprine for myasthenia gravis during the last 2 years. Acute cholestatic injury was diagnosed. After ruling out most common causes of cholestasis, azathioprine was withdrawn and subsequent histological findings in liver biopsy were consistent with drug-induced cholestatic liver damage. After discontinuation of azathioprine, biochemical parameters progressively normalised and remarkable clinical improvement was achieved. With this report, we suggest that azathioprine should be considered among the causes of liver injury, despite long treatment duration. Drug-induced liver injury (DILI) is the most common cause of acute liver failure in high-income countries.1 Most cases are idiosyncratic and involve immune-mediated mechanisms which are independent of the dose used. In population-based studies, the incidence of DILI ranges between 13.9 and 19.1 cases per 100.000 people per year,1 a figure likely flawed by systematic under-reporting. Identification of the liable drug and its prompt discontinuation are critical to achieve patient recovery. Azathioprine is an immunosuppressive drug that works by inhibiting lymphocyte proliferation, thus limiting inflammatory and autoimmune responses. Azathioprine is a well-known cause of DILI, with an incidence of 1 case per 1103 users.2 Most cases of azathioprine-induced liver injury have been reported between the first month3 4 and the first year5–12 of treatment, while only a few cases of DILI have been described in long-term users of azathioprine.13 14 In the present …