Hepatotoxicity of Immunosuppressive Drugs

doi:10.1016/B978-0-12-387817-5.00031-5

Drug-Induced Liver Disease (Third Edition)

2013, Pages 569-591

https://doi.org/10.1016/B978-0-12-387817-5.00031-5 Get rights and content

Hepatotoxicity due to immunosuppressive drugs is a rare cause of DILI, but when these reactions do occur, they run the gamut of clinical laboratory and histopathological presentations. As some immunosuppressive drugs are used less now than previously (like corticosteroids and azathioprine) and some not at all (like daclizumab that is no longer marketed), new agents are being produced at a fast rate. In the complicated setting in which these agents are usually used, many other causes of liver dysfunction are possible and indeed probable; therefore patients must be evaluated thoroughly and alternative diagnosis/diagnoses made before attributing the liver injury to immunosuppressive DILI. Sometimes there are characteristic histopathological abnormalities that provide a diagnosis but, even in these cases, concomitant causes of liver injury should still be sought. As with DILI in other situations, there is a great need for more information about patient monitoring, early detection, noninvasive tests, and, most of all, laboratory methods to identify DILI specifically and not simply by exclusion. The complicated diseases for which these drugs are prescribed and the increasing ingenuity of these agents continue to provide both a challenge and a fascination to physicians caring for these patients.

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The formal diagnosis of autoimmune hepatitis requires a liver biopsy showing a diffuse T-cell infiltrate in all lobes, prominent sinusoidal histiocytic infiltrates and central vein damage with endothelitis. Patients should be treated with corticosteroids, (Johncilla et al., 2015 Aug) and in steroid-refractory cases, adding an alternative immunosuppressive agent is in accordance with the management of autoimmune hepatitis (Johnson et al., 1995; Kaplowitz and DeLeve, 2013). Severe hepatotoxicity is more frequent when combining immunotherapy with chemotherapy or target therapy (Table 2).
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Chapter 31 - Hepatotoxicity of Immunosuppressive Drugs