Liraglutide-Induced Autoimmune Hepatitis

Abstract

he incidence and prevalence of diabetes mellitus in the United States is increasing rapidly.1 Eleven unique drug classes have been approved by the US Food and Drug Administration for type 2 diabetes mellitus. 1 Incretin-based hypoglycemic agents, including the glucagon-like peptide 1 (GLP-1) agonists and the dipeptidyl peptidase-4 inhibitors, have recently received considerable press. The US Food and Drug Administration released a statement heightening provider awareness of potential adverse events after data linking these drugs to an increased risk for pancreatic cancer surfaced. 2 Despite these warnings, the American Association of Clinical Endocrinologists guidelines 3 recommend the use of incretin mimetic drugs early in the process of intensifying glycemic control.Incretin-based hypoglycemic agents have also been implicated in cases of hepatotoxic effects. 4,5 Identifying drug-induced liver injury (DILI) is challenging, because cases are rare and can have variable presentations, including hepatic steatosis, acute liver failure, hepatic necrosis, cholestatic hepatitis, and autoimmune hepatitis (AIH). 6 A drug's hepatotoxic potential is often recognized only after approval by the US Food and Drug Administration. 6 We present the first case, to our knowledge, of drug-induced marker-negative AIH associated with liraglutide (Victoza; Novo Nordisk), a GLP-1 agonist approved in 2010 for type 2 diabetes mellitus. Report of a CaseA young Hispanic woman with a medical history of type 2 diabetes mellitus and vitiligo presented with nausea, emesis, and acute hepatitis of 10 days' duration. Other than switching drug therapy from exenatide, 10 μg twice daily, to liraglutide, 1.2 mg/d, 4 months before presentation, the patient reported no changes in medication use or use of herbal supplements or acetaminophen. For the last 3 years she had taken metformin hydrochloride, 500 mg twice daily, and used topical tacrolimus ointment, 0.1%, for her vitiligo. Her social history was unremarkable other than recent travel to the southern United States. Physical examination findings included mild scleral icterus but no evidence of advanced liver disease, abdominal tenderness, or altered mentation.

Pharmacokinetics in Patients with Chronic Liver Disease and Hepatic Safety of Incretin-Based Therapies for the Management of Type 2 Diabetes Mellitus

“…In a recent pilot Japanese study, treatment with liraglutide had a good safety profile and significantly improved liver function and histological features in NASH patients with glucose intolerance [70] . A clinical case of suspected liraglutide-induced autoimmune hepatitis has been recently reported [71] . Although caution is required when interpreting the causal relationship of such event [37] , further postmarketing studies are needed to define the hepatotoxic potential of liraglutide and other GLP-1 receptor agonists.…”

An Exceedingly Rare Case of Liraglutide-Induced Liver Injury

“…In our literature search, we identified a case of liraglutide-induced autoimmune hepatitis reported by Kern et al; however, the patient's condition did not improve after stopping liraglutide, and the patient eventually needed long-term corticosteroid therapy [ 15 ]. Lack of improvement after discontinuation of the drug in this case suggests autoimmune hepatitis independent of the drug use or liraglutide triggered underlying liver condition [ 16 ].…”

Drug-Induced Liver Injury: Highlights and Controversies in the Recent Literature

“…The LEAD trial compared 48 weeks of subcutaneous liraglutide (1.8 mg/day) to placebo in 52 patients with biopsy-proven non-alcoholic steatohepatitis and was shown to significantly improve steatosis and hepatocyte ballooning on biopsy [84]. The product label of liraglutide does not mention liver injury as an adverse event and only one case report of serious liver injury was reported with liraglutide, which presented as autoimmune hepatitis that did not improve with drug discontinuation [85]. Maor et al reported a case of a 52-year-old female patient with obesity who was treated with liraglutide for weight loss for 3 months [86].…”