Drug-induced liver injury: from pathogenesis to treatment

The article presents data on classification, pathogenesis, clinical picture, diagnosis and differentiated treatment tactics, as well as practical algorithm for recognizing and preventing the development of drug-induced liver injury. Pathogenesis of drug-induced liver injury is analyzed, mechanisms of drug metabolism are explained, metabolism phases are described. Four main mechanisms of the pathological effect of drugs on the liver are identified: direct toxic effect on hepatocytes; toxic effect of drug metabolites; immunoallergic liver injury; idiosyncrasy. Peculiar attention is paid to the pathogenesis of drug-induced cholestasis. Direct hepatotoxic reactions develop according to the cytolytic (hepatocellular, parenchymal), cholestatic or mixed option. The most commonly diagnosed clinical variant of drug-induced liver injury is drug-induced hepatitis. Five forms of hepatitis induced by the use of pharmacological agents are distinguished: drug-induced hepatitis with an isolated increase in transaminases (anti-TB drugs, methyldopa, amiodarone, statins); acute hepatitis with jaundice; pseudo-surgical form of acute hepatitis: abdominal pain, fever, jaundice, enlarged gall bladder (cytostatics, antidepressants, antiarrhythmic drugs); severe forms of acute hepatitis with liver failure; chronic drug hepatitis. International diagnostic criteria, basic data on morphological liver changes are presented. Action of ursodeoxycholic acid is explained. It has a litholytic, anticholestatic, cytoprotective, immunomodulating, anti-inflammatory, antitoxic, hypocholesterolemic effect, modulates apoptosis, has a differentiated effect on the regeneration of hepatocytes.

Drug Hepatitis At AINS

Hepatic lesions induced by drugs include extremely diverse various clinical, biological and histological manifestations that can determine acute or chronic hepatobiliary disease. The term of hepatitis is recommended to be used when there is a histological confirmation. In the last decades a 11 time increase of the hepatic lesions induced by drugs is reported, due both to the increase of the number of used drugs but also by their more frequent recognition. We carried out a combined retrospective study and longitudinally prospective study that included patients with drug hepatitis. In our study there were 83 cases of drug hepatitis at AINS, which represents 33.46 % of the total number of 248 patients with drug hepatitis. In our study the highest drug hepatitis at AINS were Nimesulid (24 cases), followed by Diclofenac (21 cases), and the fewest at Piroxicam (9 cases). All the cases from the study were symptomatic, showing the increase of the cytolysis enzymes and sometimes cholestasis enzymes (mainly GGT). The average age at diagnosis was 60.1 years for the 248 patients, being lower for the male gender (57.47 years), compared to the female gender (61.26 years). Women were affected in the highest degree, 69.35% being women and 30.64% men. In our study drug hepatitis by hepatic cytolysis was dominant, more frequent than the cholestatic ones.