Introduction: High-dose glucocorticoids are being used as a standard pule therapy for a variety of critical conditions such as multiple sclerosis (MS) relapsing. Although they are considered to be safe for liver, few evidences have reported toxic liver injury after administration of high-dose Methylprednisolone (MP), related to drug-induced liver injury (DILI), autoimmune hepatitis (AIH), or viral hepatitis activation, which are difficult to distinguish accurately.

The present paper reported a case of a 38-year-old female who referred for liver enzymes elevation (ALT) level of higher than 2000 U/L together with clinical features of hepatitis, few weeks after receiving pulse MP for three episodes between 2013 and 2019, for MS-relapsing. In the first episode of taking beta-interferon, she was approached as DILI, whereas in the second and third episodes, she scored 15 and 17 according to the AIH scoring system, and was prescribed Azathioprine and Prednisolone according to probable AIH. However, she took only Ursodeoxy cholic acid (UDCA) in the second episode, and Azathioprine plus prednisolone for less than one month in the third. Her clinical features and laboratory tests were improved without specific intervention several weeks after MP discontinuation. Liver biopsy didn’t confirm specific diagnosis.

After exclusion of viral hepatitis due to persistent negative serological tests, DILI and AIH were the two possible diagnoses for this patient. The same clinical features and recovery periods in all three episodes showed that despite the possibility of AIH, MP-related DILI could be considered as a more probable cause of liver injury in our case.