Drug-induced liver injury: from pathogenesis to treatment

Abstract

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.