A Rare Case of Drug-Induced Liver Injury (DILI) From Topiramate

A 72-year-old male individual with a past medical history of seizures and ongoing management with topiramate for two months presented at the emergency department with jaundice. Ten days before the presentation, the patient started feeling fatigued and had intermittent generalized mild pain (grade 3/10) with dark-brown discoloration of urine. On physical examination, he was normotensive at 124/54 with a pulse rate of 72 beats per minute. His weight was 73.9 kg, with an average body mass index of 20.93 kg/m2. Physical examination revealed scleral icterus and diffuse jaundice all over his body, otherwise unremarkable. On laboratory work-up, the patient had elevations in alanine aminotransferase at 74.6 U/L and aspartate aminotransferase at 498 U/L. He also had extremely high alkaline phosphatase (ALP) at 1,353 U/L, total bilirubin was 10.9 mg/dL while his direct bilirubin was 8.1 mg/dL, lactate dehydrogenase (LDH) was mildly high at 300 U/L, Gamma-glutamyl transferase (GGT) was high at 1,274 U/L. Ammonia levels were found to be mildly high at 48 umol/L. His hemoglobin was 12.3 g/dL, at his baseline. Carbohydrate antigen 19-9 was slightly high at 71 U/mL, and alpha-fetoprotein was high at 10.9 ng/mL. An ultrasound of the abdomen showed no evidence of gallstone, gallbladder wall thickening, or common duct dilatation. Computed tomography (CT) scan with intravenous contrast of the abdomen and pelvis showed hepatic steatosis with borderline size liver (17 cm). A previous CT scan two months prior also showed normal liver and gallbladder. Magnetic resonance imaging (MRI) and magnetic resonance cholangiopancreatography (MRCP) showed consistent results with CT scans. Topiramate was then tapered and then discontinued. During follow-up three months after discharge, his alanine aminotransferase (ALT), aspartate aminotransferase (AST), ALP, total bilirubin, and direct bilirubin all came back to normal. Drug-induced liver injury with topiramate is rare. Most previous studies and case reports have presented liver injury with topiramate only when combined with other antiepileptic drugs (AEDs), antipsychotics, or other hepatotoxic drugs. However, the case shows that topiramate can independently cause drug-induced liver injury. The timing of the onset of jaundice in our patient, coinciding with the initiation of topiramate, suggests a possible drug-induced liver injury, and so does discontinuation of the drug improved liver enzymes. Given that only a tiny percentage of patients on topiramate develop significant liver injury, this case highlights the need for vigilance in monitoring liver function in patients initiating this medication.