Diagnosis of medicinal lesions of the liver

Medicinal liver damage is most often caused by antibiotics, nonsteroidal anti-inflammatory drugs (NSAIDs), cardiovascular and neuro- and psychotropic drugs, i.e. In fact, all modern medicines. It should be assumed that damage to the liver can cause any medicine, and if necessary, contact the manufacturers and the organizations responsible for the safety of the drugs used.

Interrogating the patient or his relatives, it is necessary to find out the dose, the way and duration of taking medications, applying them in the past.

The drug damage to the liver is usually manifested after 5 to 90 days after the start of the drug. The positive effect of drug cancellation is indicated in cases when there is a decrease in the activity of transaminases by 50% within 8 days after discontinuation of its reception. Repeated drug intake is unacceptable. However, repeated liver damage in case of accidental administration serves as evidence of hepatotoxicity of the drug.

Exclude liver disease of another etiology: hepatitis (A, B, C) and autoimmune liver disease, as well as obstruction of the biliary tract.

In difficult cases, liver biopsy can help in diagnosis. For medicinal lesions of the liver are characterized by fatty liver, granulomas, bile duct infection, zonal necrosis, nonspecific changes in hepatocytes.

[1], [2], [3], [4], [5], [6], [7]

Necrosis of hepatocytes of zone 3

Damage to liver cells is rarely due to the drug itself; it is usually called its toxic metabolite. Enzymes that metabolize drugs, activate the chemically stable form of the drug, turning it into polar metabolites. These metabolites - powerful alkylating, arylating or acetylating agents - covalently bind to liver molecules necessary for the vital activity of the hepatocyte, and as a result, necrosis develops. Subsequently, the stores of detoxifying intracellular substances, in particular glutathione, begin to deplete. In addition, oxidative reactions involving cytochrome P450 produce metabolites with an unpaired electron - the so-called free radicals. They can covalently bind to proteins and unsaturated fatty acids of cell membranes and, by causing lipid peroxidation (LPO), lead to their damage. As a result, as a result of excessive concentration of calcium in the cytosol and suppression of the mitochondrial function, the hepatocyte dies. Necrosis is most pronounced in zone 3, where the highest concentration of enzymes metabolizing drugs is observed, and the oxygen pressure in the blood of the sinusoid is minimal. The fatty liver of hepatocytes develops, however, the inflammatory reaction is not very pronounced.

Tactics for medicinal liver damage

	Notes
Suspicion of any medicinal product	Contact the manufacturer and the organizations responsible for the safety of the medicines used
Medical history	Find out all the drugs taken, doses, duration, reception in the past
Termination of admission	Rapid reduction of transaminase levels
Repeat reception	Usually a random intake of the drug; deliberate reception is rare
Exclusion of other liver diseases	Hepatitis A, B, C and autoimmune; biliary obstruction
Liver biopsy	If necessary; characteristic fatty liver, granuloma, zonal hepatitis, bile duct disease

Liver necrosis depends on the dose of the drug. This condition can be reproduced in animal experiments. Other organs are affected, and kidney damage is the most important. In mild cases, mild transient jaundice is noted. Biochemical research reveals a significant increase in the activity of transaminases. Rapidly increasing PV. With light microscopy in the liver, clearly delimited necrosis zone 3, diffuse fat changes and a light inflammatory reaction. Occasionally, marked periportal fibrosis is detected. A typical example of such a reaction is paracetamol intoxication.

The severity of zone 3 necrosis may be disproportionate to the dose of the drug taken. The mechanism of necrosis in such cases can not be explained by the direct cytotoxic action of the drug; suggest idiosyncrasy to its metabolites. Halothane sometimes causes fused zonal or massive necrosis, as well as an inflammatory reaction. Products of reduced metabolism, which occurs both with oxidation and with the reduction of the drug, can have high reactivity. Regardless of the way of formation, all metabolites can bind to cellular macromolecules and cause LPO and inactivation of enzymes, both participating in the metabolism of drugs, and not participating in it.