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Risk factors for drug-induced liver injury
Last reviewed: 04.07.2025
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Liver diseases
Impaired drug metabolism depends on the degree of hepatocellular insufficiency; it is most pronounced in cirrhosis. T 1/2 of the drug correlates with prothrombin time, serum albumin level, hepatic encephalopathy and ascites.
There are many reasons for the disruption of drug metabolism. It can be caused by a decrease in blood flow in the liver, especially when it comes to drugs that are metabolized during the first pass. There is a disruption of oxidation processes, especially when using barbiturates and elenium. Glucuronidation is usually not disrupted, so the release of morphine, which is a drug with high clearance and is normally inactivated by this route, remains unchanged. However, glucuronidation of other drugs is disrupted in liver diseases.
With decreased albumin synthesis by the liver, the binding capacity of plasma proteins decreases. This delays the elimination of, for example, benzodiazepines, which are characterized by a high degree of protein binding and are excreted almost exclusively by biotransformation in the liver. In hepatocellular disease, the clearance of the drug from the plasma decreases, and its volume of distribution increases, which is associated with a decrease in protein binding.
In liver diseases, increased sensitivity of the central nervous system to certain drugs, especially sedatives, may be associated with an increase in the number of receptors in it.
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Age and gender
In children, reactions to drugs are rare, except in cases of overdose. It is even possible that resistance exists; for example, in children with paracetamol overdose, liver damage is much less severe than in adults with similar serum paracetamol concentrations. However, hepatotoxicity has been observed in children with sodium valproate, and in rare cases with halothane and salazopyrine.
In older people, the excretion of drugs that undergo mainly phase 1 biotransformation is reduced. This is not due to a decrease in cytochrome P450 activity, but to a decrease in liver volume and blood flow in it.
Drug reactions with liver damage are more common in women.
The fetus has very few or no P450 enzymes. After birth, their synthesis increases and their distribution within the lobule changes.