A 60-year-old woman with relapsing multiple sclerosis presented from her long-term care facility with altered mental status, fatigue, anorexia, and jaundice. She had been started on teriflunomide therapy (14 mg daily) nine months prior, at which point liver tests (LTs) were normal.
On arrival, she was afebrile, tachycardic, and normotensive, without an oxygen requirement. Labs were significant for aspartate transaminase (AST) of 1,499 U/L, alanine aminotransferase (ALT) of 777 U/L, alkaline phosphatase (AP) of 478 U/L, and total bilirubin (Tbil) of 2.5 mg/dL, without significant abnormalities on complete blood count or chemistry panel. The INR was 1.20. Lactate and lipase were normal, acetaminophen level was <2 ug/ml, and COVID-19 and influenza A and B were negative. Initial CT and abdominal ultrasound showed nonspecific hepatic echogenicity, patent hepatic vessels, and no abnormalities in the biliary system. Teriflunomide was discontinued immediately upon admission given the black box warning for hepatotoxicity, and she was admitted for workup. Hepatitis and herpes serologies were negative. Antinuclear antibody, liver-kidney microsomal antibody, immunoglobulin G levels, alpha-1 antitrypsin, serum protein electrophoresis, and iron levels were normal. Rheumatologic workup was notable for a positive smooth muscle antibody with a titer of 1 : 40, which was thought to be clinically insignificant. Ferritin was significantly elevated at 28,754 ng/ml; however, MRI with iron quantification showed no evidence of iron overload. Hemochromatosis gene testing revealed heterozygosity for the H63D mutation, a genotype that has not been clearly associated with symptoms of hereditary hemochromatosis. In combination with the MRI and other lab results, this was not thought to be clinically significant. Over the course of admission, AST and ALT trended down, but AP, Tbil, and INR continued to rise. ERCP with EUS and liver biopsy were performed on hospital day 5. Biopsy was most consistent with drug-induced injury, with a minor component of steatohepatitis. Teriflunomide was the suspected culprit drug, and the patient was treated with cholestyramine 4 grams every 6 hours for accelerated elimination starting on hospital day 7. LTs dropped consistently across all lab markers by hospital day 10 (Table 1). Teriflunomide was discontinued indefinitely at the time of discharge back to her long-term care facility. At one month follow-up, LTs were markedly improved (Table 1).