Clinical hepatotoxicity. Regulation and treatment with inducers of transport and cofactors.
Drug-induced liver injury (DILI) is a rare condition. This review presents a clinical update on the incidence and prevalence of DILI, cellular targets and histopathological features of liver injury, and basic diagnostic approaches. At present, with the exception of acetaminophen poisoning where timely administered N-acetylcysteine serves as the antidote, treatment usually is supportive. Since most biotransformation processes in the liver are under the control of nuclear receptors (NR), treatment modalities aiming to stimulate or inhibit NR expression are at present tested in animal models of APAP toxicity or cholestasis. Some NR ligands have also been used in human cholestatic liver disease, but studies on the efficacy in DILI are lacking. This review describes possible future options for the treatment of DILI.
Marschall
Hanns-Ulrich
HU
Karolinska Institutet, Department of Medicine, Karolinska University Hospital Huddinge, Stockholm, Sweden. hanns-ulrich.marschall@ki.se
Wagner
Martin
M
Zollner
Gernot
G
Trauner
Michael
M
D000818:Animals; D000931:Antidotes / Q000627:therapeutic use; D056486:Chemical and Drug Induced Liver Injury / Q000188:drug therapy*; D002779:Cholestasis / Q000188:drug therapy; D006801:Humans; D008024:Ligands; D018160:Receptors, Cytoplasmic and Nuclear / Q000819:agonists / Q000037:antagonists & inhibitors / Q000187:drug effects*
D000931:Antidotes; D008024:Ligands; D018160:Receptors, Cytoplasmic and Nuclear