Azathioprine-induced hepatitis and cholestasis occurring 1 year after treatment

Abstract

Azathioprine is an immunosuppressive medication used in the management of many autoimmune conditions. Commonly reported adverse effects from azathioprine therapy are nausea and bone marrow suppression, while less common side effects include hepatotoxicity. We present the case of a 47-year-old man with a history of myasthenia gravis on azathioprine for 1 year, who presented to our institution with painless jaundice. On initial laboratory evaluation, the level of aspartate aminotransferase, alanine aminotransferase and total bilirubin were markedly elevated. Owing to the potential diagnosis of acute liver failure secondary to azathioprine toxicity, this medication was discontinued. A liver biopsy demonstrating drug-induced liver injury, along with high serum levels of 6-methylmercaptopurine nucleotide confirmed the diagnosis of azathioprine-induced hepatotoxicity. Upon discontinuation of the medication, the patient's transaminases and bilirubin levels improved steadily over the four-day hospital course. This case emphasises azathioprine's potential for hepatotoxicity, even 1 year after the initiation of its use.

BAFF-driven B cell hyperplasia underlies lung disease in common variable immunodeficiency

“…Rituximab was previously reported to be efficacious in combination with azathioprine for 7 CVID ILD patients; however, comparison with those receiving supportive therapy or rituximab monotherapy was not included (45). Broadly immunosuppressive agents, like azathioprine, can be hepatotoxic, lead to significant gastrointestinal symptoms, promote malignancy, and increase risk of infection, particularly in patients already immunocompromised by CVID (46)(47)(48)(49). Furthermore, there is no clear therapeutic endpoint or indication when immunosuppression should be stopped or restarted prior to clinical worsening.…”

Drug-induced liver injury in inflammatory bowel disease: 1-year prospective observational study

“…Drug induced cholestatic liver injury has been described in IBD patients treated with azathioprine or less commonly by anti-TNF therapy[ 19 , 20 ]. Symptomatic cholestatic hepatitis has been reported in patients on high-dose azathioprine[ 21 ]. Milder liver injuries might also present as cholestasis.…”

Safety and efficacy of mizoribine treatment in nephrotic syndrome complicated with hepatitis B virus infection: a clinical study

“…2,3 Leflunomide and azathioprine exhibit liver toxicity, and, therefore, are contraindicated for the treatment of HBV-positive nephrotic syndrome. 3,4 MZR is an imidazole nucleoside that specifically inhibits the division and proliferation of T and B cells, resulting in humoral and cellular immune suppression. [5][6][7] As a new immunosuppressant, MZR is devoid of tumorigenicity and gonadal suppression effects, and with low bone marrow inhibition and hepatotoxic effects.…”

“…A draft of MZR (150-200 mg/d), methylprednisolone (0.6-0.8 mg/kgÁd), and entecavir (0.5 mg/d) was administered to study patients over 24 weeks. The serum albumin (AlB), 24-h urine protein (24-U-TP), liver and renal functions, and HBV-DNA were quantified before and at 2,4,8,12,16,20, and 24 weeks after the treatment. The adverse responses were recorded.…”