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Most of the available drugs cause drug-induced liver injury (DILI) to variable extents with heterogeneous clinical and biological manifestations, including liver injury with or without signs of hypersensitivity and autoimmunity. The diagnosis of DILI may be particularly difficult because MS is frequently associated with idiopathic autoimmune hepatitis. Recent advances suggest that MS and immune-mediated DILI could be promoted by genetic factors, including HLA genotype. In addition, some of these drugs may promote hepatitis B virus reactivation. This review explores the potential hepatotoxicity of drugs used to treat MS and the criteria to distinguish DILI from idiopathic autoimmune hepatitis associated with MS. The role of susceptible genes both promoting MS and causing the hepatotoxicity of the drug used for MS treatment is also discussed.<\/jats:p>","DOI":"10.3390\/ijms24010852","type":"journal-article","created":{"date-parts":[[2023,1,4]],"date-time":"2023-01-04T04:28:17Z","timestamp":1672806497000},"page":"852","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Hepatotoxicity of Drugs Used in Multiple Sclerosis, Diagnostic Challenge, and the Role of HLA Genotype Susceptibility"],"prefix":"10.3390","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5697-286X","authenticated-orcid":false,"given":"Lucy","family":"Meunier","sequence":"first","affiliation":[{"name":"Liver and Transplantation Unit, Montpellier School of Medicine, 34080 Montpellier, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0892-3489","authenticated-orcid":false,"given":"Dominique","family":"Larrey","sequence":"additional","affiliation":[{"name":"Liver and Transplantation Unit, Montpellier School of Medicine, 34080 Montpellier, France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,1,3]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"162","DOI":"10.1016\/S1474-4422(17)30470-2","article-title":"Diagnosis of Multiple Sclerosis: 2017 Revisions of the McDonald Criteria","volume":"17","author":"Thompson","year":"2018","journal-title":"Lancet Neurol."},{"key":"ref_2","first-page":"29","article-title":"A Case of Multiple Sclerosis with Atypical Onset Associated with Autoimmune Hepatitis and Silent Coeliac Disease","volume":"29","author":"Franciotta","year":"2008","journal-title":"Neurol. 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