Diseases of the liver and biliary tract

Primary biliary cirrhosis of the liver

Primary biliary cirrhosis of the liver is an autoimmune liver disease that begins as chronic destructive non-purulent cholangitis, which lasts for a long time without pronounced symptoms, leading to the development of prolonged cholestasis and only in the later stages to the formation of liver cirrhosis.

Cirrhosis of the liver

Liver cirrhosis is a chronic polyetiological diffuse progressive liver disease characterized by a significant decrease in the number of functioning hepatocytes, increasing fibrosis, restructuring of the normal structure of the parenchyma and vascular system of the liver, the appearance of regeneration nodes and the subsequent development of liver failure and portal hypertension.

Acute drug-induced hepatitis

Acute drug-induced hepatitis develops in only a small proportion of patients taking the drugs and occurs approximately 1 week after the start of treatment. The likelihood of developing acute drug-induced hepatitis is usually impossible to predict. It does not depend on the dose, but increases with repeated use of the drug.

Hepatotoxicity of paracetamol

In adults, liver necrosis develops after taking at least 7.5-10 g of the drug, but the actual dose of the drug is difficult to estimate, since vomiting develops quickly, and anamnesis data are unreliable.

Hepatotoxicity of carbon tetrachloride

Carbon tetrachloride can enter the body accidentally or as a result of suicidal ingestion. It can be in gas form (for example, during dry cleaning or when filling a fire extinguisher) or mixed with drinks.

List of hepatotoxic drugs

Alcohol consumption significantly increases the toxicity of paracetamol: significant liver damage is possible with just 4-8 g of the drug. Apparently, the reason for this is the induction of P450-3a (P450-II-E1) by alcohol, which plays an important role in the formation of toxic metabolites. In addition, it is involved in the oxidation of nitrosamines in the alpha position.

Diagnosis of drug-induced liver damage

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

Risk factors for drug-induced liver injury

Impaired drug metabolism depends on the degree of hepatocellular insufficiency; it is most pronounced in cirrhosis. The drug T1/2 correlates with prothrombin time, serum albumin level, hepatic encephalopathy and ascites.

Drug metabolism in the liver

The major drug metabolizing system is located in the microsomal fraction of hepatocytes (in the smooth endoplasmic reticulum). It includes mixed-function monooxygenases, cytochrome C reductase, and cytochrome P450. The cofactor is reduced NADP in the cytosol. Drugs undergo hydroxylation or oxidation, which enhances their polarization. An alternative phase 1 reaction is the conversion of ethanol to acetaldehyde by alcohol dehydrogenases, found mainly in the cytosol.

Chronic drug-induced hepatitis

Symptoms of chronic active hepatitis can be caused by medications. These include oxyphenisatin, methyldopa, isoniazid, ketoconazole, and nitrofurantoin. Older women are most often affected.

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