Acute Liver Failure after Natalizimab Infusion: Case Report and Review of Literature

Background: Natalizumab is a recombinant monoclonal antibody against α4 integrin for treatment of Relapsing Remitting forms of Multiple Sclerosis (RRMS). In the post marketing setting cases of hepatotoxicity including severe liver injury have been described. The etiology of liver dysfunction is unknown but postulated to be unmasking auto immune hepatitis.

Objectives:  To present a case of a young woman with RRMS who developed acute liver dysfunction after second infusion of Natalizimab and review of the literature.

Methods:  Case Report

Results: A 26 years old woman with no significant past medical history or toxic habits was diagnosed with aggressive form of RRMS; A year after of diagnosis her relevant clinical manifestations were severe truncal ataxia, and prominent gait difficulty. Magnetic Resonance Image (MRI) of the brain showed T1 enhancing lesions of the subcortical white matter as well as FLAIR/T2 lesions in periventricular areas, brainstem and cerebellum. Due to the severity of her disease she received 5 days of Plasma Exchange followed by maintenance treatment with Natalizimab 300 mg every 28 days with good response to this therapy; two weeks after her second infusion she developed nausea, vomiting, severe jaundice, and choluria. Her liver function tests showed AST 1076 (15-56), ALT 856 (11-50), Alkaline phosphatase 165 (39-117), Total bilirubin 24.9 (0-1), conjugated bilirubin 15.7 (0-0.3). Anti-Mitochondrial and anti-nuclear antibodies were negative but anti-smooth muscle antibodies were weakly positive 1:20 (<1:20). Liver ultrasound ruled out biliary obstruction. Follow up studies continued to show significant elevation of her liver enzymes and bilirubin. Full results and outcomes will be exposed at the conference.

Review of literature demonstrates at least 11 cases of severe Natalizumb-associated liver injury. In a post marketing study four out of six patients developed significant liver dysfunction after the first infusion. The mechanism of lesion is unknown but in some cases pathological reports suggest being immune mediated.

Conclusions:  Natalizumab can precipitate severe liver dysfunction, often after the first or second infusion; the exact mechanism of injury is unknown but possible immune mediated. Clinically implications and recommendations will be provided.