Dissecting the molecular pathophysiology of drug-induced liver injury.

Dissecting the molecular pathophysiology of drug-induced liver injury.
World J Gastroenterol. 2018 Apr 07;24(13):1373-1385
Authors: Ye H, Nelson LJ, Gómez Del Moral M, Martínez-Naves E, Cubero FJ
Abstract
Drug-induced liver injury (DILI) has become a major topic in the field of Hepatology and Gastroenterology. DILI can be clinically divided into three phenotypes: hepatocytic, cholestatic and mixed. Although the clinical manifestations of DILI are variable and the pathogenesis complicated, recent insights using improved preclinical models, have allowed a better understanding of the mechanisms that trigger liver damage. In this review, we will discuss the pathophysiological mechanisms underlying DILI. The toxicity of the drug eventually induces hepatocellular damage through multiple molecular pathways, including direct hepatic toxicity and innate and adaptive immune responses. Drugs or their metabolites, such as the common analgesic, acetaminophen, can cause direct hepatic toxicity through accumulation of reactive oxygen species and mitochondrial dysfunction. The innate and adaptive immune responses play also a very important role in the occurrence of idiosyncratic DILI. Furthermore, we examine common forms of hepatocyte death and their association with the activation of specific signaling pathways.
PMID: 29632419 [PubMed - in process]

Source: World Journal of Gastroenterology - April 7, 2018 Category: Gastroenterology Authors: Ye H, Nelson LJ, Gómez Del Moral M, Martínez-Naves E, Cubero FJ Tags: World J Gastroenterol Source Type: research