Hepatitis is a general term to describe inflammation of the liver tissue. Although it can arise from several causes, hepatitis from a viral infection is the most common. Alcoholic hepatitis is a severe syndrome whereby inflammation of the liver is caused by alcohol consumption.
Alcoholic Hepatitis. Image Credit: Victor Moussa/Shutterstock.com
Alcohol and alcoholic liver disease
Alcoholic liver disease (ALD) is a general term that refers to the damage caused to liver tissue by alcohol overconsumption. It encompasses a range of diseases, including steatosis (fatty liver disease), cirrhosis, and alcoholic hepatitis (AH). AH is a severe form of ALD and usually progresses to liver cirrhosis as alcohol consumption continues.
AH can recede if drinking is discontinued, but once cirrhosis has occurred, the damage to the liver is irreversible. ALD is the most common reason for liver transplants in the United States. According to the National Institute on Alcohol Abuse and Alcoholism (NIAAA), AH is defined by:
- The onset of jaundice occurring within 60 days of a minimum 6-month period of heavy alcohol consumption.
- A level of serum bilirubin, which refers to the concentration of bilirubin in the bloodstream, of more than 3 milligrams per deciliter (mg/dL) as compared to a normal result of 1.2mg/dL.
- Elevated aspartate aminotransferase (AST) levels from a typical range of 5-40 units per liter of serum to between 50 – 400 units per liter. AST is an enzyme found mostly in the liver which is released into the blood if the liver is damaged.
- An AST/ALT ratio (the ratio between the concentration of AST and alanine aminotransferase, another enzyme indicative of liver damage) of 1.5 or higher.
- No viral cause for hepatitis.
Clinically, the commonest symptom of AH is the presence of jaundice, but other symptoms include anorexia, fever, nausea and vomiting, and fatigue. Due to a loss of appetite from ALH, malnutrition is also common in people with AH.
Causes of AH
AH is a preventable disease that is caused by the ongoing consumption of more alcohol than the liver can process. The liver is the body’s main site for the metabolism of alcohol, with three enzyme systems responsible for the oxidization of alcohol. These include the cytosolic alcohol dehydrogenase (ADH) system, the microsomal ethanol-oxidizing system (MEOS), and the peroxisomal catalase system. The product of all three systems is a reactive metabolite called acetaldehyde, which damages liver tissue in a variety of ways.
One mechanism is via the generation of free radicals and inhibition of antioxidant defenses. Free radicals are oxygen-containing molecules that are a normal by-product of energy production by cells. In high concentrations, they can damage cell membranes and proteins causing tissue damage. Antioxidants are molecules that neutralize free radicals, and oxidative stress occurs when there is an imbalance between free radicals and antioxidants, leading to inflammation and cell damage.
Alcohol, therefore, damages the liver indirectly as it is metabolized. However, it can also directly damage liver cells by altering the movement of other enzymes and transport proteins.
How much alcohol causes AH?
The amount of alcohol necessary to induce AH is unknown, and likely to vary between individuals. Although it is most commonly observed in people aged between 40-60 years, it has been reported in patients in their 20’s, up to patients in their 80’s. Whilst the estimated minimum daily alcohol intake necessary for the development of AH is between 20 – 40 grams daily, typically patients provide a history of over 80 grams daily, over five years.
Who is at risk?
Whilst there is strong evidence to suggest a genetic susceptibility to developing alcohol misuse disorder, the role of genetics in progressing to AH is unclear. Only a small percentage of people with heavy alcoholism develop AH. However, research has shown that the following factors influence the risk of developing the disease:
Sex
Women are more vulnerable to AH as they absorb and metabolize alcohol differently than men. Women have a lower amount of body water, and higher amount of body fat, thus they achieve higher concentrations of alcohol in the bloodstream than men after consuming equivalent levels of alcohol. They also metabolize alcohol from the blood at a faster rate than men.
Obesity
The presence of obesity significantly increases the likelihood of AH, due to the synergy between alcohol and body fat. For example, fatty acids from adipose (fat cell) tissue contribute to liver inflammation, and cytokine inflammation in adipose tissue is closely correlated with inflammation in liver tissue.
Ethnicity
In the United States, research has compared the severity of AH and cirrhosis on White versus non-White patients. It has shown that African American and Hispanic patients with cirrhosis were likely to have a two-fold elevation in AST compared to White patients. Hispanic people with AH are also more likely to develop features of cirrhosis than African American and White people with AH.
Can AH be prevented?
Whilst avoiding all alcohol consumption is the only way to eliminate the risk of AH, reducing drinking to a moderate amount can reduce the risk. Taking care not to consume alcohol with other potentially liver-toxic medications and taking steps to prevent infection from Hepatitis C will also reduce the likelihood of developing AH.
References:
- Basra, G., Basra, S., & Parupudi, S. (2011). Symptoms and signs of acute alcoholic hepatitis. World journal of hepatology, 3(5), 118–120. https://doi.org/10.4254/wjh.v3.i5.118
- Gustot, T., & Jalan, R. (2019). Acute-on-chronic liver failure in patients with alcohol-related liver disease. Journal of hepatology, 70(2), 319–327. https://doi.org/10.1016/j.jhep.2018.12.008
- Levy, R., Catana, A. M., Durbin-Johnson, B., Halsted, C. H., & Medici, V. (2015). Ethnic differences in presentation and severity of alcoholic liver disease. Alcoholism, clinical and experimental research, 39(3), 566–574. https://doi.org/10.1111/acer.12660
- https://www.niaaa.nih.gov/
- Shah NJ, Royer A, John S. Alcoholic Hepatitis. [Updated 2020 Nov 20]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2021
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