Development of Blood Biomarkers for Drug-Induced Liver Injury: An Evaluation of Their Potential for Risk Assessment and Diagnostics

Abstract

Drug-induced liver injury (DILI) remains a rare but serious complication in drug therapy that is a primary cause of drug failure during clinical trials. Conventional biomarkers, particularly the serum transaminases and bilirubin, serve as useful indicators of hepatocellular or cholestatic liver injury, respectively, but only after substantial and sometimes irreversible tissue damage. Ideally, more sensitive biomarkers that respond very early before irreversible injury has occurred would offer improved outcomes. Novel biomarkers are initially being developed in animal models exposed to intrinsically hepatotoxic stimuli. However, the eventual translation to human populations, even those with known risk factors that predispose the liver to drug toxicity, would be the fundamental goal. Ultimately, some might even be applicable for the early identification of individuals predisposed to idiosyncratic hepatotoxicity potential. This article reviews recent progress in the discovery and qualification of novel biomarkers for DILI and delineates the path to eventual utilization for risk assessment. Some major categories of plasma or serum biomarkers surveyed include proteins, cytokines, circulating mRNAs, and microRNAs.

Efficacy of coupled low-volume plasma exchange with plasma filtration adsorption in treating pigs with acute liver failure: A randomised study

“…The majority of animal models for drug-induced liver injury are often exposed to lethal levels of chemical stress, with changes in pro-inflammatory cytokines expression, such as TNF-α, IL-1β, IL-6, and IL-10 [47][48][49]. Inflammatory cytokines may perpetuate liver damage and extend the inflammatory cascade, thereby compromising other organs [50].…”

Protective effect of ursodeoxycholic acid, resveratrol, andN-acetylcysteine on nonalcoholic fatty liver disease in rats

“…Serum ALT and AST are among the most sensitive biochemical markers investigated in the diagnosis of liver diseases and the best indicators of liver necrosis (Amacher et al, 2013). Interestingly, serum ALT level was higher than serum AST level in the steatosis group (Table 1), where the elevated serum ALT level, but not AST, was corrected by either drug treatment.…”

New microRNA Biomarkers for Drug-Induced Steatosis and Their Potential to Predict the Contribution of Drugs to Non-alcoholic Fatty Liver Disease

“…Therefore, the development of new biomarker strategies and approaches is essential. Recently, circulating miRNAs have been studied as emerging biomarkers that promise early response and increased sensitivity (Amacher et al, 2013). These features are particularly relevant for DILI as conventional biomarkers, such as the serum transaminases and bilirubin, are induced only after significant liver damage has already occurred.…”