Biomarkers for drug-induced liver injury

Abstract

Abstract:The liver plays a central role in metabolizing xenobiotics; therefore, it is highly susceptible to toxicity from these chemicals. Certain drugs, when taken in overdose and sometimes even when used within therapeutic range, may cause injury to the organ. Druginduced liver injury is now not only a leading cause of acute liver failure in the US, but is also a leading reason for discontinuation of drugs in development and for regulatory actions against previously approved drugs. The current clinical biomarkers to detect and monitor drug-induced liver injury are inadequate in terms of sensitivity and/or specificity, prompting the need for more informative biomarkers. The development of high throughput proteomics, genomics, and metabolomics technologies has the potential to fulfill such demand. The discipline of systems toxicology may add to our understanding of perturbed xenobiotic networks, which may lead to network-specific surrogate markers and therapeutic means to stop or reverse xenobiotic-induced liver injury.

Preventive use of a hepatoprotectant against anti‐tuberculosis drug‐induced liver injury: A randomized controlled trial

“…Third, although we used multiple biomarkers including ALT, AST, TBiL, GGT, and ALP to identify ATLI, we cannot guarantee the detection of liver injury at a very early stage. 33 Fourth, this study was open labeled. Information bias was unavoidable because of the lack of blinding.…”

Emerging Efforts for Discovering New Biomarkers of Liver Disease and Hepatotoxicity

“…Numer ous prospective biomarkers of liver disease and hepatotoxicity have been explored, but only a handful have survived to be developed, qualified, approved and then deployed in clinical practice. Biomarkers in the clinic have narrow applicabil ity as providers of cautionary signals, but lacking specificity, generally, and the ability to predict disease etiology, particularly [2]. Despite prodi gious effort, 'goldstandard' biomarkers of liver disease and hepatotoxicity have not yet emerged [3].…”

Biomarkers of drug-induced liver injury

“…In addition, the predictive value for these genetic biomarkers to DILI is yet to be determined. 3,11 Thus, at the present time, testing patients for the presence of susceptible genetic polymorphisms before prescribing a drug with potential DILI has very low clinical value. 48,49 However, as more and more information is collected, it will be feasible to have a comprehensive pharmacogenetic test prior to prescribing certain drugs to determine an individual's susceptibility to DILI, just like the association between CYP2C9 polymorphism and warfarin usage.…”

“…The most commonly used aminotransferases for detecting DILI are glutamic pyruvate transaminase (GPT, also known as alanine aminotransferase) and glutamic-oxaloacetic transaminase, (GOT, also known as aspartate aminotransferase). 3 Due to its molecular size, the half-life of GPT in serum is about 40-60 hours. 58 An elevation of serum GPT activity is therefore an indication of damage that has occurred within the past 40-60 hours.…”

“…1 It has been estimated that about 10% of drugs are associated with severe, undesirable side effects. 2,3 However, the number is probably significantly underestimated given that drug-induced adverse effects are difficult to detect due to pre-existing medical conditions, multiple drug usage, and lack of diagnostic standards. 1 Among all the major organs in the body, most drug-induced adverse effects are associated with the liver due to its active role in metabolizing xenobiotics.…”