Liver injury associated with the β-interferons for MS

Abstract

To the Editor: Hepatotoxicity has been associated with all forms of interferon beta.1 Autoimmune hepatitis (AIH), another hepatic complication of IFN (beta)-1a treatment for MS, has been reported.2 We present an unusual case. A 52-year-old woman with a 10-year history of multiple sclerosis (MS) was initially treated with glatiramer acetate from 1997 to 1999. In January 2000, IFN beta-1a (Avonex) was started after relapsing symptoms occurred and new MRI lesions appeared. In December 2002, she developed painless jaundice, a cholecystectomy was performed, and her jaundice resolved. Avonex was continued. Hepatic function tests were normal in February 2003. IFN beta-1a (Rebif) was instituted in early May 2003 because of worsening gait and progressive MRI changes. The patient received 8.8 mcg SC (20% of target dose) every other day for only six doses until she noted increasing fatigue and jaundice. There was no history of acetaminophen, ethanol, or nefazodone use. Physical examination revealed marked jaundice. Laboratory tests showed increased hepatic enzymes and total bilirubin of 28.6 mg/dL (0.2 to 1.3 mg/dL). Hepatitis panel and thyroid function tests were normal. ANA screen was positive in a 1:320 homogenous pattern. Anti-smooth antibodies were positive at 1:40 titer. A CT of the abdomen revealed no biliary obstruction. Prednisone 20 mg/day was administered. Over the next several months there was a dramatic decrease in jaundice and bilirubin levels, and by March 2004 the total bilirubin was 0.8 mg/dL. Autoimmune complications have been reported in MS patients treated with interferon alpha and interferon beta after several months.2–4⇓⇓ The etiology of this immunologic complication is unclear but may involve disruption of vital intracellular functions, induction of antibody cytotoxicity, or mitochondrial …