ALCOHOL-RELATED LIVER DISEASE

ALCOHOL-RELATED LIVER DISEASE

Alcohol-related liver disease (ARLD) refers to liver damage caused by excess alcohol intake. There are several stages of severity and a range of associated symptoms. 

Epidemiology and Risk Factors of Alcohol-Related related liver disease (ARLD) 

What is known about the epidemiology of liver disease has changed due to a better understanding of nonalcoholic fatty liver disease and chronic viral hepatitis. 

The prevalence of alcoholic liver disease (ALD) is difficult to define because it is influenced by many factors, including genetic (e.g., predilection to alcohol abuse, gender) and environmental (e.g., availability of alcohol, social acceptability of alcohol use, concomitant hepatotoxic insults) factors. In the United States, it is estimated that 67.3% of the population consumes alcohol and that 7.4% of the population meets the criteria for alcohol abuse. The use of alcohol varies widely throughout the world, with the highest use in the U.S. and Europe. Men are more likely to develop ALD than women because men consume more alcohol. However, women are more susceptible to alcohol hepatotoxicity and have twice the relative risk of ALD and cirrhosis compared with men. The Elevated body mass index is also a risk factor in ALD and nonalcoholic fatty liver disease. 

Ethnicity and genetics are key factors related to ALD. Cirrhosis mortality is higher in men of Hispanic, Native American, and native Alaskan origin compared with white populations. Genetic factors such as the presence of the patatin-like phospholipase domain containing 3 (PNPLA3) gene appear to be associated with a more severe phenotype and a poor prognosis. 

In general, the risk of liver disease increases with the quantity and duration of alcohol intake. The quantity of alcohol in alcoholic beverages varies by volume based on the type of beverage (Table 2). 

Table 2. Alcohol Content by Type of Alcoholic Beverage 

Although alcohol use is necessary for ALD, excessive alcohol use does not necessarily promote ALD. In heavy drinkers, only 1 in 5 develops alcoholic hepatitis and 1 in 4 develops cirrhosis. 

Fatty liver is a universal finding among heavy drinkers and up to 40% of those with moderate alcohol intake (10–80 mg/day) also exhibit fatty liver changes. Based on an autopsy series of men, a threshold daily alcohol intake of 40 g is necessary to produce pathologic changes of alcoholic hepatitis. Consumption of over 80 g of alcohol per day is associated with an increase in alcoholic hepatitis severity but not overall prevalence. There is a clear dose-dependent relation between alcohol intake and the incidence of alcoholic cirrhosis. A daily intake of more than 60 g of alcohol in men and 20 g of alcohol in women significantly increases the risk of cirrhosis. In addition, daily drinking, as compared with binge drinking, appears to be more harmful. 

Pathophysiology Of Alcohol-Related related liver disease 

The liver and, to a lesser extent, the gastrointestinal tract are the main sites of alcohol metabolism. There are two main pathways of alcohol metabolism in the liver: alcohol dehydrogenase and cytochrome P450 (CYP) 2E1. Alcohol dehydrogenase is a hepatocyte-cytosolic enzyme that converts alcohol to acetaldehyde. Acetaldehyde is subsequently metabolized to acetate via the mitochondrial enzyme acetaldehyde dehydrogenase. CYP 2E1 also converts alcohol to acetaldehyde.

Liver damage occurs through several interrelated pathways. Alcohol dehydrogenase and acetaldehyde dehydrogenase cause the reduction of nicotinamide adenine dinucleotide (NAD) to NADH (a reduced form of NAD). The altered ratio of NAD/NADH promotes a fatty liver through the inhibition of gluconeogenesis and fatty acid oxidation. CYP 2E1, which is upregulated in chronic alcohol use, generates free radicals through the oxidation of nicotinamide adenine dinucleotide phosphate (NADPH) to NADP. Chronic alcohol exposure also activates hepatic macrophages, which then produce tumor necrosis factor-alpha (TNF-alpha). TNF-alpha induces mitochondria to increase the production of reactive oxygen species. This oxidative stress promotes hepatocyte necrosis and apoptosis, which is exaggerated in the alcoholic who is deficient in antioxidants such as glutathione and vitamin E. Free radicals initiate lipid peroxidation, which causes inflammation and fibrosis. Inflammation is also incited by acetaldehyde, which, when bound covalently to cellular proteins, forms adducts that are antigenic.

Symptoms of alcohol-related liver disease (ARLD) 

ARLD does not usually cause any symptoms until the liver has been severely damaged.

When this happens, symptoms can include: 

• feeling sick 
• weight loss 
• loss of appetite 
• yellowing of the whites of the eyes or skin (jaundice) 
• swelling in the ankles and tummy 
• confusion or drowsiness 
• vomiting blood or passing blood in your stools 

This means ARLD is frequently diagnosed during tests for other conditions or at a stage of advanced liver damage. 

If you regularly drink alcohol to excess, tell your GP so they can check if your liver is damaged. 

Alcohol and the liver 

The liver is one of the most complex organs in the body.  

Its functions include: 

• filtering toxins from the blood 
• aiding digestion of food 
• regulating blood sugar and cholesterol levels 
• helping fight infection and disease 

The liver is very resilient and capable of regenerating itself. Each time your liver filters alcohol, some of the liver cells die. 

The liver can develop new cells, but prolonged alcohol misuse (drinking too much) over many years can reduce its ability to regenerate. This can result in serious and permanent damage to your liver. 

ARLD is common in the UK. The number of people with this condition has been increasing over the last few decades due to increasing alcohol misuse. 

Stages of ARLD 

There are 3 main stages of ARLD, although there is often an overlap between each stage. These stages are explained here. 

Alcoholic fatty liver disease 

Drinking a large amount of alcohol, even for just a few days, can lead to a build-up of fat in the liver. 

This is called alcoholic fatty liver disease and is the first stage of ARLD. 

Fatty liver disease rarely causes any symptoms, but it is an important warning sign that you are drinking at a harmful level. 

Fatty liver disease is reversible. If you stop drinking alcohol for some time (months or years), your liver should return to normal. 

Alcoholic hepatitis 

Alcoholic hepatitis, which is unrelated to infectious hepatitis, is a potentially serious condition that can be caused by alcohol misuse over a longer period. 

When this develops, it may be the first time a person is aware they are damaging their liver through alcohol. 

Less commonly, alcoholic hepatitis can occur if you drink a large amount of alcohol in an abbreviated period (binge drinking). 

The liver damage associated with mild alcoholic hepatitis is usually reversible if you stop drinking permanently. 

Severe alcohol hepatitis, however, is a serious and life-threatening illness. 

Many people die from the condition each year in the UK, and some people only find out they have liver damage when their condition reaches this stage. 

Cirrhosis 

Cirrhosis is a stage of ARLD where the liver has become significantly scarred. Even at this stage, there may not be any obvious symptoms. 

It is not reversible, but stopping drinking alcohol immediately can prevent further damage and significantly increase your life expectancy.

Treating alcohol-related liver disease (ARLD) 

There is currently no specific medical treatment for ARLD. The main treatment is to stop drinking, preferably for the rest of your life. 

This reduces the risk of further damage to your liver and gives it the best chance of recovering. 

If a person is dependent on alcohol, stopping drinking can be difficult. 

But support, advice and medical treatment may be available through local alcohol addiction support services. 

A liver transplant may be required in severe cases where the liver has stopped functioning and does not improve when you stop drinking alcohol. 

You will only be considered for a liver transplant if you have developed complications of cirrhosis despite having stopped drinking. 

All liver transplant units require people with ARLD to not drink alcohol while awaiting the transplant and for the rest of their life. 

Complications 

Death rates linked to ARLD have risen over the last few decades. 

Alcohol misuse is now one of the most common causes of death in the UK, along with smoking and high blood pressure. 

Life-threatening complications of ARLD include: 

• internal (variceal) bleeding 
• build-up of toxins in the brain (encephalopathy) 
• fluid accumulation in the abdomen (ascites) with associated kidney failure 
• liver cancer 
• increased vulnerability to infection 

Preventing alcohol-related liver disease (ARLD) 

The most effective way to prevent ARLD is to stop drinking alcohol or stick to the recommended limits: 

• men and women are advised not to regularly drink more than 14 units a week 
• spread your drinking over 3 days or more if you drink as much as 14 units a week 
• if you want to cut down, try to have several drink-free days each week 

A unit of alcohol is equal to about half a pint of normal-strength lager or a pub measure (25ml) of spirits. 

Even if you have been a heavy drinker for many years, reducing or stopping your alcohol intake will have important short-term and long-term benefits for your liver and overall health.