The Potential Role of Metabolomics in Drug-Induced Liver Injury (DILI) Assessment

Abstract

Drug-induced liver injury (DILI) is one of the most frequent adverse clinical reactions and a relevant cause of morbidity and mortality. Hepatotoxicity is among the major reasons for drug withdrawal during post-market and late development stages, representing a major concern to the pharmaceutical industry. The current biochemical parameters for the detection of DILI are based on enzymes (alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma-glutamyl transpeptidase (GGT), alkaline phosphatase (ALP)) and bilirubin serum levels that are not specific of DILI and therefore there is an increasing interest on novel, specific, DILI biomarkers discovery. Metabolomics has emerged as a tool with a great potential for biomarker discovery, especially in disease diagnosis, and assessment of drug toxicity or efficacy. This review summarizes the multistep approaches in DILI biomarker research and discovery based on metabolomics and the principal outcomes from the research performed in this field. For that purpose, we have reviewed the recent scientific literature from PubMed, Web of Science, EMBASE, and PubTator using the terms “metabolomics”, “DILI”, and “humans”. Despite the undoubted contribution of metabolomics to our understanding of the underlying mechanisms of DILI and the identification of promising novel metabolite biomarkers, there are still some inconsistencies and limitations that hinder the translation of these research findings into general clinical practice, probably due to the variability of the methods used as well to the different mechanisms elicited by the DILI causing agent.

Simultaneous Elimination of Reactive Oxygen Species and Activation of Nrf2 by Ultrasmall Nanoparticles to Relieve Acute Kidney Injury

“…GGT is one of preclinical/clinical biomarkers for predicting liver injury induced by drugs. 55 However, a mild increase of GGT shows less clinical significance if the key indices such as AST, AST, and ALP are normal. 56 A slight increase in GGT could be due to the influence of CSPQ NPs on liver.…”

“…There was only a slight increase in GGT among all the indicators (Figure c–f). GGT is one of preclinical/clinical biomarkers for predicting liver injury induced by drugs . However, a mild increase of GGT shows less clinical significance if the key indices such as AST, AST, and ALP are normal .…”

Molecular and Clinical Links between Drug-Induced Cholestasis and Familial Intrahepatic Cholestasis

“…For example, studies conducted on patients with ALF have an iDILI etiology in 11% of cases (excluding acetaminophen overdose), and 64% die or undergo liver transplantation (LT) [ 1 ]. iDILI is the most frequent indication of LT in Europe and the US and the first cause of ALF [ 2 ].…”

“…The incidence and relevance of iDILI are continuously increasing due to the ongoing development of new drugs, the increase in life expectancy, the prescription of polytherapy in the elderly, and the use of herbal products (which cause the so-called Herb-Induced Liver Injury, HILI) [ 2 ].…”

Metabolomics in Team-Sport Athletes: Current Knowledge, Challenges, and Future Perspectives

“…This application in sports was recently defined with the term “sportomics” [ 6 ]. In the last decade, exercise metabolomics studies were conducted on runners [ 7 ], cyclists [ 8 ], soccer players [ 9 , 10 ], basketball players [ 11 ], and rugby players [ 12 ]. Indeed, exercise physiologists know well that exercise primes one for significant, often profound variations in the metabolism of numerous tissues and organs.…”