Drug-induced liver injury (DILI) - mechanisms and diagnostic

Abstract

The drug-induced liver injury (DILI) is one of the leading causes of the liver disease in developed countries. These injuries may be the result of constant drug hepatotoxicity or idiosyncrasy associated with the drug or its metabolite. The constant hepatotoxicity of a drug is related to its mechanism of action, so it is predictable and dose-dependent (the classic example that causes the greatest amount of the liver damage in Western countries is paracetamol). Idiosyncratic reactions are difficult to predict and occur rarely, which makes them very harmful. As the liver is not only an important gland in the digestive system, but also one of the most important organs for the body, its damage causes a large number of complications with often very serious consequences. The diagnosis of the drug-induced liver injury is independent of the cause of the liver injury and is based on a relatively small number of available laboratory tests. Currently, the "gold standard" in predicting severe drug-induced liver injury is Hy's law, that is, comparing ALT activity and bilirubin concentration in the presence of a jaundice. Improving the detection efficiency of DILI is necessary both for the safety of patients at a risk of the liver injury and for the development of methods for assessing potential hepatotoxicity of drugs during the research phase. Among the new potential DILI biomarkers we can distinguish glutamate dehydrogenase, HMGB1 protein (High-Mobility Group Box-1) as well as keratin-18 (K18) and microRNA-122 (miR-122). Despite the growing awareness of the toxicity of certain drugs, the drug-induced liver injury is still a very serious problem in the Western world. This demonstrates the need to continuously educate people about the possible side effects of their medications and dietary supplements. An accurate diagnosis of DILI requires establishing a causal relationship with the suspected factor and excluding other possible causes of the liver damage. Administration of drugs causing idiosyncratic liver damage should take place under the strict control of the liver markers so as to react as quickly as possible in the event of an idiosyncratic reaction. Further research on new biomarkers is needed, so that their potential introduction as the DILI diagnostic standard is supported by the best scientific evidence and allows for a reliable diagnosis.

Keywords

• liver injury
• biomarker
• hepatotoxicity
• dili
• idiosyncrasy