Thalidomide-Induced Severe Hepatotoxicity

Abstract

Thalidomide is a relatively safe and efficacious form of therapy in the treatment of advanced, refractory multiple myeloma. Hepatotoxicity is listed as an extremely rare adverse effect associated with its use. We describe a 76-year-old woman with multiple myeloma who was treated with dexamethasone and thalidomide. By week 6 of therapy, she had developed acute increases in her aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels to more than 50 times the upper limit of normal. Her liver function test results had been within the normal ranges before and immediately after the start of therapy, and the patient had no known history of underlying liver disease. A liver biopsy specimen demonstrated evidence of acute injury with chronic changes of underlying steatosis and bridging fibrosis due to previously undiagnosed nonalcoholic steatohepatitis. Immediately after discontinuing thalidomide, her liver function test results began trending downward. Seven days later, her AST and ALT levels had improved to 86 and 165 U/L, respectively. This case and a limited number of other reports demonstrate severe hepatotoxicity as a rare but potentially serious adverse effect of thalidomide therapy. With the expanding use of thalidomide as a therapeutic agent, clinicians must recognize severe hepatotoxicity as a potential complication. Whether patients with preexisting liver disease are at increased risk when receiving thalidomide remains to be seen.

Thalidomide Treatment in Cirrhotic Patients with Severe Anemia Secondary to Vascular Malformations

“…Thalidomide-induced hepatotoxicity has been previously reported [8], as well as constipation in 57% of the patients treated with thalidomide due to hepatocarcinoma [9]. However, these events do not justify the episodes of encephalopathy observed in our patients, which requires further research.…”

Adjuvant role of anti-angiogenic drugs in the management of head and neck arteriovenous malformations

“…Severe cases of hepatotoxicity have been reported in the literature, but liver diseases represent a non-absolute criterion of exclusion [8,[19][20][21][22][23].…”

Liver failure due to relapsed myeloma and hepatic iron overload

“…Treatment outcomes in multiple myeloma patients continue to improve with the use of immunomodulatory agents (IMiD) (e.g., thalidomide, lenalidomide and pomalidomide), proteosome inhibitors [(PI) e.g., bortezomib, carfilzomib, ixazomib], and more recently the use of immunotherapy (e.g., daratumumab and elotuzumab). Although rare, all approved IMiD therapies, including thalidomide, lenalidomide and pomalidomide, have been associated with severe hepatotoxicity during the treatment of multiple myeloma [13][14][15]. Similarly, all proteasome inhibitors have also been reported to exhibit an association with reversible liver dysfunction.…”