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One of the characteristics of <jats:styled-content style=\"fixed-case\">IDILI<\/jats:styled-content> is that it occurs rarely and only in a subset of individuals with a presumed susceptibility to the drug. Despite a clear association between single nucleotide polymorphisms in human leukocyte antigen (<jats:styled-content style=\"fixed-case\">HLA<\/jats:styled-content>) genes and certain drugs that cause <jats:styled-content style=\"fixed-case\">IDILI<\/jats:styled-content>, not all individuals with susceptible <jats:styled-content style=\"fixed-case\">HLA<\/jats:styled-content> genotypes develop clinically significant liver injury when exposed to drugs. The adaptation hypothesis has been put forth as an explanation for why only a small percentage of susceptible individuals develop overt <jats:styled-content style=\"fixed-case\">IDILI<\/jats:styled-content> and severe injury, while the majority with susceptible genotypes develop only mild abnormalities that resolve spontaneously upon continuation of the drug. This spontaneous resolution is referred to as clinical adaptation. Failure to adapt or defective adaptation leads to clinically significant liver injury. In this review we explore the immuno\u2010tolerant microenvironment of the liver and the mechanisms of clinical adaptation in <jats:styled-content style=\"fixed-case\">IDILI<\/jats:styled-content> with a focus on the role of immune\u2010tolerance and cellular adaptive responses.<\/jats:p>","DOI":"10.1111\/liv.12988","type":"journal-article","created":{"date-parts":[[2015,10,20]],"date-time":"2015-10-20T14:42:48Z","timestamp":1445352168000},"page":"158-165","source":"Crossref","is-referenced-by-count":127,"title":["Mechanisms of adaptation and progression in idiosyncratic drug induced liver injury, clinical implications"],"prefix":"10.1111","volume":"36","author":[{"given":"Lily","family":"Dara","sequence":"first","affiliation":[{"name":"Research Center for Liver Disease Keck School of Medicine University of Southern California Los Angeles CA 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