Original article| Volume 42, 102065, July 2020

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Liver injury after methylprednisolone pulse therapy in multiple sclerosis is usually due to idiosyncratic drug-induced toxicity rather than autoimmune hepatitis


      • Liver injury may develop up to 3 months after methylprednisolone (MP) pulse therapy.
      • Liver biopsy in most cases revealed drug-induced acute hepatitis.
      • In only one case, autoimmune hepatitis was triggered by MP pulse therapy.
      • Prognosis was good in most cases except for the one with autoimmune hepatitis.



      In patients with multiple sclerosis (MS), development of hepatic injury has been sporadically reported after methylprednisolone (MP) pulse therapy. Some studies suggest autoimmune hepatitis, while other studies reported direct hepatotoxicity as a cause for hepatic injury. Here, we studied the pathological mechanism of such liver injury in patients with MS.


      From 2005 to 2016, eight patients with MS developed liver injury after MP pulse therapy. Their average age was 38 years (range: 28–49 years, all female). Autoimmune antibodies were measured and a liver biopsy was performed in seven patients.


      Liver injury developed within two weeks in two patients and later (30–90 days after MP) in six patients. No hepatitis-related autoantibody or hepatitis virus were found. All cases were classified as hepatocellular injury and none as cholestatic or mixed. A liver biopsy in five cases revealed centrilobular necrosis with lobular infiltrates of inflammatory cells, suggesting drug-induced acute hepatitis. The biopsy findings in another case suggested a residual stage of acute hepatitis. Only one patient showed portal expansion with periportal fibrosis, suggesting autoimmune hepatitis. All patients recovered spontaneously or with only hepatoprotective drugs, although one patient with possible autoimmune hepatitis recovered slowly.


      Liver injury develops usually later than two weeks after MP treatment. The prognosis is good in most cases and rarely autoimmune hepatitis may be involved.



      AIH (autoimmune hepatitis), ALP (alkaline phosphatase), ALT (alanine aminotransferase), AM (Azan Mallory staining), DLST (drug-induced lymphocyte stimulation test), FLAIR (fluid-attenuated inversion recovery), HE (hematoxylin and eosin staining), MP (methylprednisolone), MRI (magnetic resonance imaging), MS (multiple sclerosis)
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