Pharmacological correction of hepatotoxicity induced by anti-tuberculosis drugs

Abstract

Drug-induced liver injury are one of the most frequent undesirable effects of drug therapy in tuberculosis patients. Hepatoprotective drugs of various origin and chemical composition are used for the correction and prevention of drug-induced liver injury. Currently, preparations of plant origin (from milk thistle, licorice, soy), animal origin, preparations of bile acids, and some others are isolated. At the same time, there is no consistent understanding of their effectiveness, as well as consistent application algorithms, since a number of drugs have been studied only in experimental or small observational clinical studies. The article presents the mechanisms of action of the main hepatoprotective drugs, provides the evidence base of their effectiveness, and also notes their shortcomings. The most studied hepatoprotective drugs in the treatment of drug-induced liver injury is milk thistle preparation, its effectiveness has been shown not only in the treatment of drug-induced liver injury, but also in their prevention, with simultaneous administration together with tuberculosis chemotherapy, mainly in patients who initially had a high risk of developing drug-induced liver injury. Glycyrrhizic acid (licorice preparation) has shown both high preventive efficacy and pronounced therapeutic effect in LPP caused by anti-tuberculosis drugs. Essential phospholipids (highly purified extract from soybeans), in combination with B vitamins, contribute to an increase in the activity and fluidity of hepatocyte membranes, their recovery, however, they have low bioavailability, ambiguous antioxidant potential and are effective only with the cholestatic nature of the lesion. Ursodeoxycholic acid preparations are highly effective – they reduce the level of hepatocyte apoptosis, prevent toxic effects on hepatocyte membranes and on the epithelium of the bile ducts, have antioxidant and choleretic effects. Ademethionine (a drug containing amino acids and their derivatives) has cytoprotective, antioxidant and anticholestatic effects, also has anti-neurotoxic and antidepressant effects. A combination of ademethionine, succinic acid, inosine and nicotinamide showed a good therapeutic effect, which allows to quickly reduce the severity of clinical symptoms of hepatotoxicity and normalize laboratory parameters. In general, the available data make it possible to effectively prevent and stop toxic liver lesions in the treatment of tuberculosis patients. A variety of hepatoprotective drugs with various pharmacological effects (anti-cytolytic, anti-cholestatic, anti-apoptotic, antioxidant, immunomodulatory) provide an opportunity for a rational choice of a drug in various clinical situations.

Keywords

• drug-induced liver injury
• hepatotoxicity
• transaminases
• hepatoprotective drugs
• tuberculosis
• essential phospholipids
• ursodeoxycholic acid