Mechanisms of Drug-induced Liver Injury

Drug-induced liver injury is typically divided into two categories: “intrinsic” and “idiosyncratic.” Intrinsic DILI is dose-dependent and usually predictable

Paul B. Watkins; Merrie Mosedale

2017

Scholarcy highlights

  • Drug-induced liver injury is typically divided into two categories: “intrinsic” and “idiosyncratic.” Intrinsic DILI is dose-dependent and usually predictable
  • Idiosyncratic DILI is difficult to predict as it has a complex dose-response relationship, its onset is typically delayed, and it is often observed in only a small percentage of treated patients
  • Both intrinsic and idiosyncratic DILI involve some level of direct drug-induced stress or injury to liver cells through three major mechanisms: mitochondrial dysfunction, oxidative stress, and alterations in bile acid homeostasis
  • In some cases of idiosyncratic hepatocellular DILI, hepatocyte stress leads to an adaptive immune response that in combination with loss of immune tolerance is responsible for clinically important liver injury
  • Preclinical animal, and computational models hold promise for guiding an improved understanding and prediction of Drug-induced liver injury

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