The hepatic safety of drugs pose a noteworthy challenge for the pharmaceutical industry all the way through the entire process of drug development. The inherent toxicity of few drugs becomes apparent during the early stages of this process, on the other hand, for majority of medications, the hepatotoxicity profile may remain hidden in both preclinical and clinical phases. Though, clinical trials report a relatively common adverse reaction, they are in general underpowered to identify the low occurrence of idiosyncratic drug-induced liver injury (DILI).

Various methods have been used to evaluate the epidemiology of DILI. Various population-based case–control studies have comprised general practice research database that allows associate prescription data to clinically meaningful events such as death, hospital admission and diagnosis at discharge. Population-based studies are a vital approach to determine the incidence of DILI, however, while considering the effect of genetic susceptibility on idiosyncratic DILI, it is difficult to evaluate the estimated risk associated with specific drugs from people with a specific genetic ancestry to populations with different genetic backgrounds.

Thus, DILI has developed as a worldwide health problem concerning transversally to a wide range of spectators ranging from clinical practitioners to several medical and surgical specialties, clinical and basic investigators, as well as people from regulatory affairs and pharmaceutical companies.  Moreover, DILI poses a huge diagnostic concern, as it is capable of mimicking any other liver disorder and is considered being a diagnosis of exclusion due to absence of biomarkers, which is seen as a major obstacle for advancing in correct phenotyping and genotyping of affected subjects. Western countries like Europe and US has introduced large DILI prospective registries in the last two decades that collect reliable information on DILI causal agents, phenotypes and risk factors, and comparable efforts in India are undergoing.

Source: Expert Opin Drug Metab Toxicol. 2016 Jun;12(6):589-93.