FRI097 A Case Of Evolocumab-induced Transaminitis Revealing A Gastrointestinal Melanoma

Disclosure: C. Nava Suarez: None. J.V. Mayrin: None. J. Prater: None. W. Jiang: None. Introduction: Proprotein convertase subtilisin/Kexin type 9 (PCSK-9) inhibitors, like evolocumab, are anti-lipid drugs with potent lipid-lowering effect, potential cardiovascular benefits, and good tolerability. They are monoclonal antibodies directed against the PCSK-9 hepatic receptor decreasing serum LDL-cholesterol. Although PCSK-9 inhibitors are usually safe, transaminitis has been reported in the literature a few times. Little is known about the mechanism of action of this injury and many clinicians are not familiar with this complication. Currently, there are no guidelines for dose adjustment in patients with advanced liver disease, and conflicting data on their effect on patients with established liver disease is emerging. We report a case of acute and intermittent transaminitis with the use of evolocumab that lead to the discovery of malignant melanoma in the patient’s gallbladder and jejunum. Case: A 74-year-old male with a past medical history of dyslipidemia, type 2 Diabetes Mellitus, and cutaneous melanoma 9 years priorly presented for a routine follow-up. He had been on evolocumab for a year after developing statin-induced myalgias. His physical exam was unremarkable. Routine blood work revealed new onset transaminitis almost 5 times above the upper limit of normal with AST 174 IU/L and ALT 230 IU/L (40 IU/L and 44 IU/L respectively). The rest of his liver panel was unremarkable. A liver ultrasound showed a 5 cm hyperechoic polypoid lesion within the gallbladder. No signs of choledocholithiasis were seen, potentially explaining the lack of bilirubin elevation; hepatic steatosis without cirrhosis was also seen. Given its higher sensitivity, MRCP confirmed the gallbladder mass. Liver enzymes were trended for more than 80 days, and intermittent elevation of serum transaminases coincided with the administration of evolocumab with normalization of the transaminases in between episodes. An open cholecystectomy confirmed the diagnosis of malignant melanoma of the gallbladder with an incidental jejunal metastasis. Oncologic treatment was initiated. Serum transaminases normalized following discontinuation of evolocumab and remain normal. Conclusion: As this case illustrates, serial monitoring of transaminases can reveal the presence of liver injury after initiation of PCSK-9 inhibitors, and further investigation with specialized liver imaging should be considered to exclude other differential diagnoses. Currently, there is little known about the hepatotoxic effect of these drugs and researchers are currently looking for possible causes. Theoretical mechanisms of injury include autoimmune cross-reactivity like with other monoclonal antibodies or progression of chronic liver disease. Clinicians should be aware of this potential side effect even though it is not a common one, given that many patients who start treatment may have underlying liver disease. Presentation: Friday, June 16, 2023