Although idiosyncratic drug-induced liver injury (IDILI) is rare, it is considered as a potentially severe adverse drug reaction. It should be highlighted in patients who develop laboratory criteria for liver injury secondary to the administration of a potentially hepatotoxic drug. It has been observed that though presently used liver parameters are sensitive in diagnosing DILI, they lack specificity and cannot predict consequent clinical course of the patient. 

Genetic risk assessment can be considered as crucial because of its high negative predictive value, with several human leucocyte antigen alleles being related to DILI. In addition, new emerging biomarkers that can play an important role in determining DILI comprise of total keratin18 (K18) and caspase-cleaved keratin18 (ccK18), macrophage colony-stimulating factor receptor 1, high mobility group box 1 and microRNA-122. 

Assessment of various available in vitro test systems, monocyte-derived hepatocytes produced from patients with DILI have shown potential in recognizing the DILI-causing agent from among a panel of coprescribed drugs. Furthermore, various computer-based algorithms are accessible that are dependent on cumulative scores of known risk factors such as the administered dose or potential liabilities including mitochondrial toxicity, inhibition of the bile salt export pump or the formation of reactive metabolites. 

Besides, a novel DILI cluster score is currently under development that can predict DILI from multiple complimentary cluster and classification models with the help of absorption–distribution–metabolism–elimination-associated as well as physicochemical properties, diverse substructural descriptors and known structural liabilities. Furthermore, validating the new diagnostic markers in the ongoing DILI registries, biobanks and public–private partnerships can bring out the window of opportunity of more advanced scientific and regulatory guidance for liver safety evaluation.

Source: Kullak-Ublick GA, Andrade RJ, Merz M, End P, Benesic A, Gerbes AL, Aithal GP. Drug-induced liver injury: recent advances in diagnosis and risk assessment. Gut. 2017 Jun;66(6):1154-1164.