Acute liver injury in a Glatopa-treated patient with MS

Case report. A 36-year-old woman presented with unilateral optic neuritis from which she recovered. Optic neuritis recurred at age 42. Brain MRI showed multiple T2-hyperintense white matter lesions and a gadolinium–diethylenetriamine penta-acetic acid– enhancing lesion. MS was diagnosed. The patient was treated with methylprednisolone 1 g/daily IV for 5 days. Concomitant medications included norethindrone/ethinyl estradiol with iron, vitamin D, calcium, and vitamin B12. The patient did not take supplements or abuse alcohol. Approximately 3 weeks later, the patient was started on generic GA. Influenza and meningococcal oligosaccharide vaccines were administered at the time she began GA. Because of symptoms of injection pain, fatigue, nausea, and constipation, the patient discontinued GA after 13 daily injections. The following day, the patient developed worsening nausea with vomiting, dyspnea with exertion, anorexia, fatigue, dark urine, and jaundice. The patient was found to have elevated liver function tests (aspartate aminotransferase 5 1,188 U/L, alanine transaminase 5 1,879 U/L, alkaline phosphatase 5 177 U/L, and total bilirubin 5 3.6 mg/dL) compared with normal values just 1 month prior (figure, A). The following laboratory values were negative or normal: HAV IgM, HBsAg, HBcAg IgG, HCV RNA, HCV antibody, HEV IgM, EBV IgM, CMV IgM, HIV, HSV PCR, urine toxicology screen, acetaminophen levels, ANA, and anti–smooth muscle antibody. HAV IgG, HBsAb, HEV IgG, and EBV IgG were positive. Twenty-four– hour urine copper (193 mg/24 h [normal range 15– 60 mg/24 h]) was presumed to be elevated secondary to acute liver injury. A liver biopsy showed severe portal, interface and panacinar, lymphocyte-predominant inflammation, with confluent necrosis, numerous apoptotic hepatocytes, and central perivenulitis (figure, B and C). The bile ducts were intact, and there was no significant ductular reaction. Steatosis, cholestasis, and fibrosis were not present. The patient was treated with IV corticosteroids followed by a several month taper of prednisone for possible autoimmune hepatitis. The patient’s liver function tests normalized within 2 months.