DRUG-INDUCED LIVER INJURY AND GENDER DIFFERENCES

Abstract

Relevance. Drug-induced liver injury (DILI) is a potentially serious clinical condition that remains a major concern for patients, physicians, and those involved in the development of new drugs. A number of studies have shown that the incidence of DILI varies from 1.4 to 19.1/100,000. Overall, women have a 1.5-1.7 times greater risk of developing adverse drug reactions, and the ratio of women to men increases after 49 years, suggesting a clear predisposition to DILI after menopause. In this regard, the study of the causes of the development of DILI depending on the sex differences of patients is relevant today. Objective: A literature review focusing on epidemiological aspects, pathogenetic mechanisms of formation, and aspects of liver injury in DILI, depending on the gender of the patients. Search strategy. The search for scientific publications was carried out in the databases of evidence-based medicine (PubMed, Scopus, Cochrane Library, Medline), in electronic scientific resources (e-Library, CyberLeninka, medical sites of neighboring countries), which revealed about 135 literary sources, 79 of them are included in this review. The search depth was 30 years (1992 - 2022). This is due to the importance of foundational fundamental works that reveal the basic issues of epidemiology, pathogenesis and diagnostic foundations for the development of DILI in representatives of various gender groups. This kind of gender-sensitive research has not been done. Inclusion criteria: the results of modern studies performed taking into account all the requirements of evidence-based medicine; data from basic fundamental studies conducted on various groups; English and Russian-language publications. Exclusion criteria: "case report"; sources earlier than 1992 that do not meet the requirements of evidence-based medicine; theses. Results: A review of sources has shown that understanding the epidemiological and pathogenetic mechanisms of the development of DILI can prevent or delay liver damage and the development of related complications, as well as allow screening and identification of risk groups for a subsequent personalized approach to the management of this group. Conclusions: The epidemiology of DILI is largely underestimated, while severity and clinical course can vary significantly across studies. It is reported that women have a 1.5-1.7 times higher risk of developing adverse drug reactions. Differences in pharmacokinetics, pharmacodynamic gene expression, or activity of drug-metabolizing enzymes may explain the observed differences between men and women, and sex hormones may also play a role.