Acute Hepatitis with Positive Autoantibodies: A Case of Natalizumab-Induced Early-Onset Liver Injury

Patient: Female, 60-year-old Final Diagnosis: Natalizumab-induced liver injury Symptoms: Jaundice • pruritus Medication: — Clinical Procedure: Drug withdrawal Specialty: Gastroenterology and Hepatology OBJECTIVE: Unusual clinical course BACKGROUND: Natalizumab is an anti-integrin monoclonal antibody used as an alternative treatment regimen for patients with autoimmune disorders, especially multiple sclerosis and Crohn’s disease. Natalizumab-induced liver injury has been rarely reported and may follow the first dose (with increases in liver enzymes usually after 6 or more days), or after multiple doses. In general, it is non-severe acute hepatitis (with a hepatocellular pattern) and autoantibodies can be positive, mainly anti-nuclear and anti-smooth muscle antibodies. CASE REPORT: We are reporting the case of a 60-year-old woman diagnosed with multiple sclerosis previously treated with interferon-beta, dimethyl fumarate, and fingolimod, who presented jaundice 1 day after the first infusion of natalizumab. She had an early-onset acute hepatitis with aminotransferases levels higher than 1000 IU/L and total bilirubin almost 41 mg/dL. Anti-nuclear and anti-smooth muscle antibodies were positive and the histo-pathological analysis of the liver showed intrahepatic cholestasis associated with moderate necroinflammatory activity (subacute cholestatic hepatitis) and mild diffuse perisinusoidal fibrosis, which could be compatible with the hypothesis of drug-induced liver injury. The scenario of an autoimmune-like hepatitis led the medical team to start oral prednisone and she progressively improved in clinical and laboratory features. Serum levels of liver enzymes and bilirubin were normal within 3 months and there was no further increase after discontinuation of corticosteroid therapy. CONCLUSIONS: Physicians should be aware of the risk of early-onset acute hepatitis in patients starting natalizumab, especially women with multiple sclerosis. Treatment with corticosteroid for a few months may be beneficial.