The liver is arguably the most fascinating organ in our bodies. It helps process toxins and food particles before they reach the blood. In addition, it helps produce various proteins including albumin, the most abundant protein in our blood, and coagulation factors. It is also very resistant to damage with a remarkable ability to regenerate. In people who donate a lobe of their liver, the liver can completely regenerate within a few weeks.
This amazing property of the liver can be impaired if the liver is flooded with injurious agents and metabolic byproducts. This is collectively known as hepatotoxicity, but most of the time, the term hepatotoxicity refers to liver damage by drugs.
How can drugs damage my liver?
Drugs are synthetic materials made by man and do not exist in nature, or rather exist in natural plants and minerals in a much lower concentration. This means that our liver is not adapted to deal with them effectively, making drugs the most common cause of fulminant hepatic failure. In fact, up to 900 medications have been identified to cause hepatoxicity. Drug-induced hepatoxicity is also the most common cause of liver transplantation.
The reason why the liver is so commonly affected is that nearly all drugs are metabolized by it. The liver contains enzymes that deal with nearly all medications taken orally. In addition, some medications are excreted in bile, which is the main fluid the liver produces. Many of those medications do not cause liver damage by themselves but are rather converted to other substances that can, and the most notable example of this phenomenon is paracetamol, which is converted into another toxic substance called NAPQI.
The main enzymes that the liver uses to metabolize drugs are called cytochromes, the most famous of which is called cytochrome P450. Many medications can even act on this enzyme, causing its activity to increase or decrease. The most common medications that cause the enzyme activity to increase are phenobarbital, phenytoin, carbamazepine, and ethyl alcohol. If another medication is metabolized by the enzyme and is taken with the previous medications, you can expect its activity and blood levels to be less. On the other hand, some medications can inhibit this enzyme, causing medications metabolized by it to reach toxic levels including antibiotics like sulfonamides, erythromycin, and isoniazid or antifungals like ketoconazole and even grapefruit.
Context is the key, and not all those medications can cause noticeable liver damage. Hepatotoxicity is related to the medication itself, the dose given, and the state of the liver at the time of administration. A dose of paracetamol that can be tolerated by a healthy person can prove fatal to one with liver cirrhosis or end-stage liver disease.