P1054 - A Rare Case of Tirzepatide-Induced Liver Injury

Achashman Berihun, MD, Aalam Sohal, MD, Kris Kowdley, MD, FACG
Liver Institute Northwest, Seattle, WA

Introduction: Tirzepatide is the first dual incretin GIP/GLP receptor activator approved for the management of Type II Diabetes mellitus (DM). This drug is also beneficial in weight loss and is gaining popularity as a potential therapeutic option for patients with diabetes and obesity. Although its benefits are well-described, no cases of tirzepatide-induced liver injury are reported.

Case Description/Methods: A 37-year-old woman with a past medical history of obesity, hypertension and hypercholesterolemia, was referred to us for elevated liver enzymes. She was asymptomatic and had a normal physical examination on presentation. She denied any alcohol or supplement use. She was initiated on tirzepatide 2.5 months prior to presentation. Her blood work on presentation revealed an alanine transaminase (ALT) of 500 U/L and aspartate transaminase (AST) of 261 U/Ll. She was negative for Hepatitis A, Hepatitis B surface antigen, hepatitis C antibody, ANA (Antinuclear Antibodies), and AMA (antimitochondrial antibody). Abdominal ultrasound was unremarkable. Anti-smooth muscle antibody (ASMA) was 37. Her ceruloplasmin and Alpha-1- antitrypsin levels were unremarkable. Tirzepatide-induced-hepatotoxicity was considered, and the drug was stopped. Her ALT and AST 3 weeks later were 110 U/L and 57 U/L respectively. The patient herself resumed tirzepatide, and 3 weeks later AST and ALT were noted to be higher(Figure 1). Tirzepatide was discontinued and a liver biopsy was ordered, which revealed benign hepatic tissue with lymphocytic infiltration within the lobules and macrophage infiltration in portal tracts. Interestingly, no steatosis was noted. Her RUCAM score was 5 (Table 1). A diagnosis of DILI (Drug Induced Liver Injury) from tirzepatide was made based on the overall presentation and she was recommended not to reinitiate tirzepatide. Her blood work 2 months later revealed an ALT of 36 U/L and AST of 24 U/L.

Discussion: We report a case of tirzepatide-induced hepatotoxicity; to our knowledge, liver injury due to tirzepatide has not been previously reported. The RUCAM score of 5, the temporal relationship of acute liver injury with the initiation of tirzepatide and positive rechallenge makes tirzepatide the probable cause of DILI. The mechanism of DILI is unclear, but it is likely that “rapid defatting” of the liver might be contributing to elevation in the liver enzymes. Providers should be aware of this association and early referral to a specialist to elucidate the cause of liver injury in these patients is needed.




Disclosures:


Achashman Berihun, MD, Aalam Sohal, MD, Kris Kowdley, MD, FACG. P1054 - A Rare Case of Tirzepatide-Induced Liver Injury, ACG 2023 Annual Scientific Meeting Abstracts. Vancouver, BC, Canada: American College of Gastroenterology.