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19 May 2022 : Case report  Brazil

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

Unusual clinical course, Challenging differential diagnosis, Unusual or unexpected effect of treatment, Diagnostic / therapeutic accidents, Unexpected drug reaction , Educational Purpose (only if useful for a systematic review or synthesis)

Marlone Cunha-Silva ORCID logo1ABCDEF, Priscilla Brito Sena de Moraes ORCID logo1ABCDEF, Pedro Rodrigues de Carvalho ORCID logo2ABEF, Larissa Bastos Eloy da Costa ORCID logo3BDEF, Guilherme Rossi Assis-Mendonça ORCID logo3BCE, Cristina Alba Lalli ORCID logo2BCE, Gisele Conte Alves Fernandes ORCID logo1BCDE, Fernanda Bocchi Monteiro ORCID logo1BDE, Gustavo Manginelli Lamas ORCID logo4BEF, Alfredo Damasceno ORCID logo4BDE, Daniel Ferraz de Campos Mazo ORCID logo1CDF, Tiago Sevá-Pereira ORCID logo1DF

DOI: 10.12659/AJCR.936318

Am J Case Rep In Press; DOI: 10.12659/AJCR.936318  

Available online: 2022-05-19, In Press, Corrected Proof

Publication in the "In-Press" formula aims at speeding up the public availability of the pending manuscript while waiting for the final publication. The assigned DOI number is active and citable. The availability of the article in the Medline, PubMed and PMC databases as well as Web of Science will be obtained after the final publication according to the journal schedule


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.
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 histopathological 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.
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.

Keywords: Chemical and Drug Induced Liver Injury; Hepatitis; Multiple Sclerosis; Natalizumab


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Am J Case Rep In Press; DOI: 10.12659/AJCR.936513  

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Am J Case Rep In Press; DOI: 10.12659/AJCR.936862  

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American Journal of Case Reports eISSN: 1941-5923
American Journal of Case Reports eISSN: 1941-5923