Alcoholic liver disease / Alcohol-related liver disease (ALD)
The harmful effects of alcohol on the human body are common knowledge. More and more people are dying of diseases related to alcohol misuse worldwide. In Croatia, 8.1% of the male and 1.9% of the female population suffer from diseases related to the misuse of alcohol, while 20.5% of males older than 15 years of age are engaged in heavy episodic drinking. Alcoholic liver disease (fatty liver, alcoholic hepatitis, fibrosis/cirrhosis), heart and kidney disorders, psychological disorders (Wernicke–Korsakoff syndrome) and carcinoma are all connected to the overuse of alcohol. Nowadays, alcohol-related liver disease is the most important health risk in developing countries and is ranked third in developed countries.
Almost all of the consumed alcohol is metabolized by the liver, which takes time. A healthy liver can metabolize 160-180 grams of ethanol in 24 hours. Ethanol is the principal ingredient of alcoholic beverages. It can damage the liver, the brain and the entire nervous system. Alcohol use changes biochemical processes in the brain at the cellular level, leading to alcohol tolerance, i.e. the need for more and more alcohol to achieve the same effect. Both physical and psychological tolerances develop side by side.
Since alcohol is metabolized by the liver, it is the organ most susceptible to alcohol-related damage. Ethanol itself is not the most dangerous substance, but its metabolites and free radicals which normally appear during the metabolic process.
While ethanol is reduced to acetaldehyde, an excess of hydrogen ions (H+) is created, thus making the microenvironment more acid. This reaction usually takes place in the cell’s cytosol. However, ethanol oxidation is also facilitated by the P450 enzyme inside the mitochondrion. One of the P450 isoenzymes, namely CYP2E1, participates in this process at higher rates than other forms of the P450 isoenzyme. The CYP2E1 isoenzyme is induced by ethanol. This means that the more alcohol a person drinks, the more ethanol is being metabolized by the mitochondria as compared to that by cytosol (the ratio is turning to the mitochondrial side). This is important since the mitochondrion and its structures, especially DNA, are less protected from the damaging potential of free radicals than the rest of the cellular structures. The excessive hydrogen ions (H+) created during ethanol oxidation into acetate are used by the mitochondria that produce ATP and water in a process called oxidative phosphorylation. Naturally, this process consumes energy derived from ethanol to create energy in the form of ATP, which is the form recognized and used by the cell for its various functions. This energy overload is just one of the ways to impede normal cellular functioning. Others include the creation of free radicals which follow the process of ethanol oxidation, first to acetaldehyde, then to acetate. Free radicals are being neutralized by antioxidants, but only up to a certain limit after which the damaging effects of free radicals starts to manifest itself. Other ways that normal cell functioning is impeded includes lipid peroxidation, enzymes inactivation, DNA mutations, and destruction of cell membranes – in short, a gradual destruction of the cell. This destruction usually shows at the organ level as liver disease, starting as fatty liver, developing to alcoholic hepatitis and fibrosis (developing fibrous tissue in place of damaged liver tissue), sometimes to cirrhosis. Fatty liver disease can also develop due to non-alcohol related causes, like obesity or diabetes. Obesity can also facilitate the development of liver fibrosis. Further drinking of alcohol can lead to cirrhosis. Research data show that age, obesity, female gender, diabetes, hemosyderosis and smoking are all factors which increase the risk of liver fibrosis.
Our body normally reacts to tissue damage by inflammation in the affected area. Inflammation serves to clear the area from damaged cells and its degradation products.
Chronic heavy drinking leads to chronic liver damage produced by free radicals. Physicians should be aware that every person consuming over 30-50 g of alcohol daily over a period of 5-10 years is at increased risk of alcohol-related liver diseases.
It is worth mentioning that the second most common cause of cirrhosis is viral hepatitis. Overuse of alcohol damages intestinal mucosa and increases permeability to macromolecules, thus contributing to an increased risk of inflammatory processes in the liver.
Research data also point to a higher risk of cancer in people who misuse alcohol. The liver is also an important part of the immune system. Therefore, a damaged liver impairs immune defense leading to a higher risk of developing cancer.
It seems that episodic heavy drinkers may have less severe, sometimes even asymptomatic, fatty liver disease. On the other hand, chronic overuse of alcohol may result in alcoholic hepatitis and alcoholic fibrosis/cirrhosis.
Besides alcohol consumption, other factors influence the risk of developing alcoholic liver disease (ALD), such as: obesity, diabetes, genetic factors, age, female gender and smoking. Finally, while susceptibility to ALD is somewhat individual, it is estimated that 90-100% of heavy drinkers will develop ALD and 8-20% of heavy drinkers will develop cirrhosis.
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