Liraglutide-induced autoimmune hepatitis

Abstract

Importance: Use of incretin-based hypoglycemic agents is increasing, but safety data remain limited. We treated a woman with marker-negative autoimmune hepatitis associated with the glucagon-like peptide 1 agonist liraglutide.

Observations: A young woman with type 2 diabetes mellitus and vitiligo presented with a 10-day history of acute hepatitis. Other than starting liraglutide therapy 4 months prior, she reported no changes in medication therapy and no use of supplements. At admission, aspartate aminotransferase level was 991 U/L; alanine aminotransferase level, 1123 U/L; total bilirubin level, 9.5 mg/dL; and international normalized ratio, 1.3. Results of a liver biopsy demonstrated interface hepatitis with prominent eosinophils and rare plasma cells. The patient's liraglutide therapy was withheld at discharge but her symptoms worsened. A second biopsy specimen revealed massive hepatic necrosis. She started oral prednisone therapy for presumed liraglutide-induced marker-negative autoimmune hepatitis.

Conclusions and relevance: This case represents, to our knowledge, the first report of liraglutide-induced autoimmune hepatitis. Hepatotoxicity may be an incretin analogue class effect with a long latency period. This case raises prescriber awareness about the potential adverse effects of glucagon-like peptide 1 agonists. Postmarketing studies are needed to define the hepatotoxic potential of these agents.

Figure 1. Results of the First Liver Biopsy

Portal and interface inflammation with a mixed inflammatory infiltrate consisting of lymphocytes, occasional plasma cells (black arrowheads), and prominent eosinophils (yellow arrowheads) are seen (hematoxylin-eosin, original magnification ×40). Inset is of the boxed area in the larger slide (original magnification ×200).

Figure 2. Results of the Second Liver Biopsy

Lobular necrosis and portal and interface inflammation with predominant lymphocytes and scattered eosinophils (yellow arrowheads) are seen (hematoxylin-eosin, original magnification ×200). Inset is taken from a portion of the biopsy not captured on the larger slide (original magnification ×400).

Figure 3. Trend in Liver Function Test Results During the Course of the Patient’s Disease

Results over time for the patient’s alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels (A) and the bilirubin level (B). The upper limit of the reference range for the ALT level is 52 U/L; for AST, 39 U/L. To convert AST and ALT to microkatals per liter, multiply by 0.0167; bilirubin to micromoles per liter, multiply by 17.104.