P1872 - The First Reported Case of Drug-Induced Liver Injury Caused by Semaglutide

Sarah Enslin, PA¹, Nicholas Bartell, MD¹, Vivek Kaul, MD, FACG^2
1University of Rochester Medical Center, Rochester, NY; ²University of Rochester Medical Center, Strong Memorial Hospital, Rochester, NY

Introduction: Drug-induced liver injury (DILI) is the most common cause of acute liver failure in the United States and accounts for ~ 10% of all cases of acute hepatitis. Many medications have been reported to cause DILI, most commonly acetaminophen, amoxicillin/clavulanate, diclofenac, amiodarone, and allopurinol. Semaglutide is a GLP-1 analogue approved for use in the United States for the management of DM2 in 2017.We present a case of semaglutide-induced liver injury. To our knowledge, this is the first case report of liver injury due to semaglutide.

Case Description/Methods: A 79yo male with history of segmental main duct IPMN s/p Whipple 6 years ago presented with fatigue and dehydration of 4 weeks duration. He had started semaglutide 6 weeks prior for management of diabetes mellitus type 2 (DM2). Laboratory (lab) tests revealed acute transaminitis (AST 310 IU/L, ALT 321 IU/L) with mild elevation of alkaline phosphatase (319 IU/L) and normal bilirubin. Abdominal ultrasound showed hepatic steatosis but no other significant findings. Serologic evaluation for autoimmune hepatitis, viral hepatitis, Wilson’s disease, hemochromatosis, and celiac disease were all negative. After a detailed review, it was felt semaglutide was likely the cause of his transaminitis. This medication was discontinued, and he reported near complete symptomatic improvement within 3 days. Repeat lab tests 1 week later had significantly improved (AST 35 IU/L, ALT 90 IU/L, ALP 219 IU/L).

Discussion: Semaglutide is a GLP-1 analogue approved in the United States in 2017. A recent phase 2 clinical trial including 320 patients demonstrated semaglutide was significantly superior to placebo for resolution of NASH, suggesting a potential role in the treatment of fatty liver disease.¹ Adverse reactions of semaglutide include injection site reactions, diarrhea, nausea, vomiting, abdominal pain, headache, fatigue and rarely pancreatitis and thyroid C-cell tumors. This is the first reported case of semaglutide-induced liver injury. Symptoms and liver tests both improved upon cessation of drug. This information has significant clinical implications given the anticipated use of this agent for a potentially large population of eligible patients with fatty liver disease.



Reference:

Newsome P N, Buchholtz K, Cusi K, et al. A Placebo-Controlled Trial of Subcutaneous Semaglutide in Nonalcoholic Steatohepatitis. New England Journal of Medicine 2021;384(12):1113-1124


Disclosures:


Sarah Enslin, PA¹, Nicholas Bartell, MD¹, Vivek Kaul, MD, FACG². P1872 - The First Reported Case of Drug-Induced Liver Injury Caused by Semaglutide, ACG 2021 Annual Scientific Meeting Abstracts. Las Vegas, Nevada: American College of Gastroenterology.