Acute Liver Dysfunction after Addition of Natalizumab to Interferon in Two Patients with MS

Kader, Michael; Mayes, Thalia; Katzman, Philip J.; Saubermann, Lawrence J.; Fazili, Bushra G.; Maliakkal, Benedict

doi:10.14309/00000434-200709002-00524

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“…Compiling the reported cases, most patients with natalizumab-induced liver injury were women diagnosed with MS and previously treated with interferon-beta, as natalizumab is used as an alternative therapeutic regimen [ 5 , 11 ]. Our patient was older than the mean age described (60 years vs 41 years), and her total bilirubin levels were higher (41 vs 25 mg/dL).…”

Section: Discussionmentioning

confidence: 99%

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

et al. 2022

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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.

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Section: Discussionmentioning

confidence: 99%