Drug-Induced Liver Injury: Biomarkers, Requirements, Candidates, and Validation

Abstract

The hepatotoxicity of drugs is the main cause of drug withdrawal from the pharmaceutical market and interruption of the development of new molecules. Biomarkers are useful in several situations. In case of suspected drug-induced liver injury (DILI), biomarkers can be used to confirm liver damage, its severity, prognosis, confirm drug causality, or define the type of DILI. In this review, we will first present the currently used biomarkers and candidate biomarkers for the future. The current biomarkers are certainly very helpful including with the assistance of diagnostic method such the Roussel Uclaf Causality Assessment Method, but provide a limited information for the early detection of liver injury, the role of specific drug and the prediction of DILI. Some biomarkers are promising but they are not yet available for routine use. Studies are still needed to confirm their interest, particularly in comparison to Roussel Uclaf Causality Assessment Method.

Diagnostic Biomarkers in Liver Injury by Drugs, Herbs, and Alcohol: Tricky Dilemma after EMA Correctly and Officially Retracted Letter of Support

“…Liver injury caused by green tea extracts shows dose dependent features but diagnostic biomarkers were not described [67]. Dose dependency can be assumed for HILI caused by phytochemicals derived from germander (Teucrium chamaedris) [17,[75][76][77][78][79], Polygonum multiflorum [68,69,80,81], and plants containing unsaturated pyrrolizidine alkaloids (PAs) [15,[82][83][84][85][86][87][88][89][90]. For these herbs, diagnostic biomarkers are known and in clinical use although test validation was rarely provided [17].…”

“…Liver injury by germander is dose-dependent and can easily be recognized using a specific diagnostic biomarker [17,[75][76][77][78][79]. Germander components undergo microsomal oxidation via CYP isoform 3A [75][76][77][78][79]. Indeed, anti-microsomal epoxide hydrolase autoantibodies have been found in the sera of patients who drank germander tea for a long period of time.…”

Treatments in Covid-19 patients with pre-existing metabolic dysfunction-associated fatty liver disease: A potential threat for drug-induced liver injury?

“…Clearly, future investigations will be required to determine which of these drugs could be involved in the elevated serum aminotransferases commonly observed in COVID-19 patients. It should be pointed out that accountability assessment in cases with suspected DILI is mainly based on chronological and clinical criteria as well as the elimination of other causes of liver injury [ 31 ]. Drug accountability can be evaluated by different methods such as the Roussel Uclaf Causality Assessment Method (RUCAM) [ 31 , 32 ].…”

“…It should be pointed out that accountability assessment in cases with suspected DILI is mainly based on chronological and clinical criteria as well as the elimination of other causes of liver injury [ 31 ]. Drug accountability can be evaluated by different methods such as the Roussel Uclaf Causality Assessment Method (RUCAM) [ 31 , 32 ]. Of note, other methodological approaches are required for causality assessment of suspected DILI in patients with pre-existing nonalcoholic steatohepatitis (NASH) [ 33 ].…”

Herb-induced Liver Injury in Asia and Current Role of RUCAM for Causality Assessment in 11,160 Published Cases

“…Herb-induced liver injury, with HILI as its acronym, was first introduced and proposed as a specific term in the scientific literature in 2011 1,2 and subsequently characterized. [3][4][5][6] Several review articles have addressed relevant issues of HILI also in relation with drug-induced liver injury (DILI). [7][8][9] Evaluating suspected HILI cases is complex, complicated, and can be a tricky undertaking because herbal medications exert an intrinsic liver injury type due to overdosed ingredients or improper herbal product quality, including adulteration or toxic contamination.…”