Memantine-Induced DILI

Abstract

Presentations of drug-induced liver injury (DILI) are highly variable. While biochemical evidence of cholestasis is common, the extent of aminotransferase elevations and patterns of liver injury vary. Asymptomatic patients may never be diagnosed. Memantine is an increasingly used therapy in Alzheimer's dementia, reported here to cause cholestatic liver injury in an elderly male. An 86-year-old man with a history of coronary artery disease, atrial fibrillation, prostate cancer, hypothyroidism, gout and Alzheimer's disease presented with incidental elevated aminotransferases up to ten times the upper limit over 2 months. He did not have fever, chills, abdominal pain, nausea, vomiting, jaundice, pruritus or mental status changes. Longstanding medications included donepezil, lisinopril, carvedilol, apixaban, atorvastatin, levothyroxine, allopurinol and omeprazole. Memantine was initiated 2 months prior to presentation. He denied history of tobacco or alcohol use. Physical exam was unremarkable including negative Murphy's sign. The serum aspartate aminotransferase (AST) was 438 U/L, alanine aminotransferase (ALT) was 439 U/L, total and direct bilirubin were 0.9 mg/dL and 0.5 mg/dL respectively, and alkaline phosphatase (ALP) was 169 U/L. Memantine was immediately discontinued. Evaluations for viral, autoimmune, and metabolic etiologies for liver injury were unremarkable, except positive ANA (1:160 dilution), normal IgG (1376 mg/dL). Right upper quadrant ultrasound revealed only cholelithiasis. Three months after memantine withdrawal, the levels of AST (168 U/L) and ALT (140 U/L) and ALP (58 U/L) decreased significantly. Six months after memantine withdrawal, all liver associated enzymes returned to normal. The diagnosis of DILI requires a strong index of suspicion, meticulous history taking and exclusion of other etiologies. This patient was asymptomatic, presenting with a hepatocellular pattern of liver injury of unclear etiology. Although autoimmune hepatitis (AIH) remained on the differential, the decision was made to forego liver biopsy given his comorbidities. The patient's Revised Original Scoring System of the International Autoimmune Hepatitis Group score was 4 (without including liver histology or response to therapy), making AIH unlikely. Memantine induced liver injury has been rarely reported in the literature. Consideration of this diagnosis should prompt immediate discontinuation of this medication while excluding other etiologies.