The Effects Of Binge Drinking On The Liver

Alcoholic liver disease (ALD) is characterized by a fatty liver, hepatitis, fibrosis, and cirrhosis. Binge drinking is on the rise worldwide, and is particularly common in the U.S. A review of studies addressing the effects of binge drinking on the liver underscores the complex interactions among various immune, signaling pathways, epigenetic, and metabolic responses of the liver to binge drinking.

Results will be published in the April 2013 issue of Alcoholism: Clinical & Experimental Research and are currently available at Early View.

"The liver is the main metabolic site in the body," said Shivendra D. Shukla, Margaret Proctor Mulligan Professor at the University of Missouri, School of Medicine as well as corresponding author for the study. "It is involved in nutrient and drug metabolism and disposition, and in the production of a myriad of agents needed for the physiological functions of organs such as the heart, kidney, blood vessels, and brain. ALD-affected liver chemicals can also influence immunity, cardiovascular health, and coagulation. Thus, ALD can have a 'domino effect' on many organs."

"The liver is also the major organ for alcohol metabolism, and as such, is the first line of defense against excessive alcohol consumption," added Samir Zakhari, senior vice president in the Office of Science at Distilled Spirits Council of the United States. "The effects of binge drinking on the liver depend on whether binge drinking is superimposed on chronic heavy drinking, or is done on an empty stomach especially after a period of fasting or starvation."

"Binge abuse is on the rise globally," said Shukla. "For example, about 43 percent of college students have reported at least one binge episode during the previous months. It is therefore necessary to fully understand its consequences at molecular levels. This is the first review that highlights the molecular pharmacology of binge drinking and how this may offer insight into binge-induced injury and its wider implications."

Some of the review's key themes are:

• Binge consumption of alcohol is implicated in the pathophysiology of ALD. New studies from both experimental animals and humans indicate that binge drinking has profound effects on immunological, signaling, and epigenetic parameters of the liver. This is in addition to the known metabolic effects of acute levels of alcohol.
• "Chronic alcohol consumption renders the liver highly susceptible to binge-induced liver damage," said Shukla. "Binge-induced liver injury impacts other organs as well, a view rather poorly appreciated by the public."
• Binge drinking alters the levels of several cellular components and dramatically amplifies liver injury in the chronically alcohol-exposed liver.

"This review, the first of its kind, emphasizes the importance of molecular and epigenetic mechanisms in binge-induced liver injury," said Shukla. "This review also sets the stage for additional investigations in this field. The cross-organ implications of binge-induced liver damage must be explored."

"Binge drinking influences all the mechanisms mentioned above, but can also cause mitochondrial damage, which may result in cell death and disturbances in bioenergetics," added Zakhari. "Therefore, people should not binge drink, especially on an empty stomach, and if they are chronic heavy drinkers, binge drinking will exacerbate liver injury, especially if comorbid conditions such as obesity, Hepatitis C, or HIV infection exist."

The authors stress the importance of additional molecular investigations into the binge effects of alcohol for a better understanding of ALD. They also suggest that future research address the development of therapeutic strategies to control binge drinking.

"Our review highlights the effects of ALD on multiple molecules that in turn have effects on various organs," said Shukla. "We hope this will encourage research and development of newer approaches and tools to control and ameliorate binge-induced health effects."

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What Is Cirrhosis? What Causes Cirrhosis?

Cirrhosis is an abnormal liver condition in which there is irreversible scarring of the liver. The main causes are sustained excessive alcohol consumption, viral hepatitis B and C, and fatty liver disease - however, there are many possible causes.

People with cirrhosis may develop jaundice (yellowing of the skin, eyes and tongue), itching and extreme tiredness.

For cirrhosis to develop long-term, continuous damage to the liver needs to occur. When healthy liver tissue is destroyed and replaced by scar tissue the condition becomes serious, as it can start blocking the flow of blood through the liver.

Cirrhosis is a progressive disease, developing slowly over many years, until eventually it can stop liver function (liver failure).

The liver carries out several essential functions, including the detoxification of harmful substances in the body. It also purifies the blood and manufactures vital nutrients.

If cirrhosis is mild the liver can make repairs and continue functioning properly. If the cirrhosis is advanced and more and more scar tissue forms in the liver, the damage is irreparable. The liver tissue is replaced by fibrous scar tissue as well as regenerative nodules (lumps that appear as a consequence of a process in which damaged tissue is regenerated).

According to Medilexicon's medical dictionary:

Cirrhosis is "A chronic liver disease of highly various etiology characterized by inflammation, degeneration, and regeneration in differing proportions; pathologic hallmark is formation of microscopic or macroscopic nodules separated by bands of fibrous tissue; impairment of hepatocellular function and obstruction to portal circulation often lead to jaundice, ascites, and hepatic failure."

What are the signs and symptoms of cirrhosis?

A symptom is something the patient feels and reports, while a sign is something other people, including a doctor or a nurse may detect. For example, pain may be a symptom while a rash may be a sign.

Symptoms are not common during the early stages of cirrhosis. However, as scar tissue accumulates the liver's ability to function properly is undermined. The following signs and symptoms may occur:

• Blood capillaries become visible on the skin on the upper abdomen
• Fatigue
• Insomnia
• Itchy skin
• Loss of appetite
• Loss of bodyweight
• Nausea
• Pain or tenderness in the area where the liver is located
• Red or blotchy palms
• Weakness

The following signs and symptoms may appear as the disease progresses:

• Abdomen fills up with fluid, giving the patient a large tummy (ascites)
• Accelerated heartbeat
• Altered personality (as blood toxins build up and affect the brain)
• Bleeding gums
• Body and upper arms lose mass
• Body finds it harder to process alcohol
• Body finds it harder to process drugs
• Confusion
• Dizziness
• Fluid buildup on ankles, feet and legs (edema)
• Hair loss
• Higher susceptibility to bruising
• Jaundice (yellowing of the skin, whites of the eyes, and tongue)
• Loss of libido (sex drive)
• Memory problems
• More frequent fevers (susceptibility to infections)
• Muscle cramps
• Nosebleeds
• Pain on the right shoulder
• Panting (breathlessness)
• Stools become black and tarry, or very pale
• Urine becomes darker
• Vomiting blood
• Walking problems (staggering)

What are the causes of cirrhosis?

The most common causes of cirrhosis are long-term alcohol abuse, hepatitis B and C infection, and fatty liver disease.

Overconsumption of alcohol

According to the NHS (National Health Service), UK, excessive alcohol consumption is when a man drinks more than 21 units and a woman drinks more than 14 units per week.

Toxins, including alcohol, are broken down by the liver. However, if the amount of alcohol is too high the liver will be overworked and liver cells can eventually become damaged.

Heavy, regular, long-term drinkers are much more likely to develop cirrhosis, compared to other healthy people. It is a myth that only alcoholics are at risk - regular and heavy social drinking is also linked to a higher probability of developing cirrhosis.

Typically, heavy drinking needs to be sustained for at least ten years for cirrhosis to develop. The period varies according to each individual.

Regular heavy female drinkers are more likely to develop symptoms compared to men who consume the same amount.

Heavy drinkers will eventually develop fatty liver. The liver breaks down alcohol into carbon dioxide and water, causing fatty liver. As soon as excessive drinking stops the symptoms of fatty liver go away. However, 20% to 30% of those who continue drinking heavily will develop alcoholic hepatitis, the next stage. Approximately 10% of heavy drinkers will subsequently develop cirrhosis - the third stage of alcoholic liver disease.

Health authorities in the UK urge males not to exceed three to four units of alcohol consumption per day, and women should not have more than two to three units daily - to reduce the risk of developing alcohol hepatitis and cirrhosis.

Hepatitis and cirrhosis

Hepatitis C, a bloodborne infection, can damage the liver and eventually lead to cirrhosis. Hepatitis C is a common cause of cirrhosis in Western Europe, North America, and many other parts of the world. Cirrhosis can also be caused by hepatitis B and D.

Non-alcoholic steatohepatitis (NASH)

NASH is more likely to occur with people who are obese, diabetes patients, those with high blood lipid (fat) levels, as well as individuals with hypertension (high blood pressure). NASH, in its early stages, begins with the accumulation of too much fat in the liver. The fat causes inflammation and scarring, resulting in possible cirrhosis later on.

Autoimmune hepatitis

The person's own immune system attacks healthy organs in the body as though they were foreign substances. Sometimes the liver is attacked. Eventually the patient can develop cirrhosis.

Some genetic conditions

• Hemochromatosis - iron accumulates in the liver and other parts of the body.
• Wilson's disease - copper accumulates in the liver and other parts of the body.

Blockage of bile ducts

Some conditions and diseases, such as cancer of the bile ducts, or cancer of the pancreas can block the bile ducts, increasing the risk of cirrhosis.

Budd-Chiari syndrome

There is thrombosis (blood clots) in the hepatic vein, the blood vessel that carries blood from the liver, leading to liver enlargement and the development of collateral vessels.

Some other diseases and conditions

• Cystic fibrosis
• Primary sclerosing cholangitis - hardening and scarring of the bile ducts
• Galactosemia - inability to process sugars in milk
• Schistosomiasis - a parasite commonly found in some developing countries
• Biliary atresia - badly formed bile ducts in babies
• Glycogen storage disease - problems in the storage and energy release vital for cell function

Diagnosis of cirrhosis

Cirrhosis in its early stages is often diagnosed when the patient is being tested for some other condition or disease because symptoms are not present.

Anybody who has the following symptoms should see their doctor immediately:

• Fever with shivering
• Panting (shortness of breath)
• Vomiting blood
• Dark stools, or tarry stools (as if covered with tar)
• Episodes of drowsiness or confusion

A GP (general practitioner, primary care physician) will examine the patient and feel around the liver area to determine whether it is enlarged. The patient will be asked about his/her medical history and lifestyle (drinking, etc).

The following tests may also be ordered:

A blood test - to measure how well the liver is functioning and determine whether there is any damage. If levels of ALT (alanine transaminase) are high the patient may have hepatitis.

Imaging tests - this may involve an ultrasound, CT (computerized tomography), or MRI (magnetic resonance imaging) scan of the liver. Apart from seeing whether the liver is enlarged, the doctor will also be able to detect any scarring.

A biopsy - a small sample of liver cells are extracted and examined under a microscope. The doctor inserts a fine needle in between the ribs and into the liver. The patient will receive a local anesthetic. The biopsy not only confirms or rules out cirrhosis, but may also reveal its cause (if it is cirrhosis).

Endoscopy - an endoscope, a long, thin tube with a light and video camera at the end goes down the patient's windpipe (esophagus) and into their stomach. The doctor sees the inside of the stomach on a screen, and looks out for swollen blood vessels (varices); a hallmark sign of cirrhosis.

Child-Pugh Score

Also known as the Child-Turcotte-Pugh score, assesses the prognosis (outlook) of chronic liver disease, mainly cirrhosis. Originally, it was used to predict mortality during surgery, but is now used to determine prognosis, as well as the required treatment strength, and whether or not the patient needs a liver transplant. It is a combination of numbered points and the letters A, B, C (see below):

Class	Points	One year survival	Two year survival
A	5-6	100%	85%
B	7-9	81%	57%
C	10-15	45%	35%

What are the treatment options for cirrhosis?

If the cirrhosis is diagnosed early enough, damage may be minimized by treating its underlying cause.

Alcohol dependency (alcoholism) treatment - it is important for the patient to stop drinking if their cirrhosis was caused by long-term, regular heavy alcohol consumption. In many cases the doctor will recommend a treatment program for alcoholism.

Medications - the patient may be prescribed drugs to control liver cell damage caused by hepatitis B or C.

Treating cirrhosis complications

Ascites or edema - ascites (accumulation of fluid in the abdomen) or edema (fluid retention in the legs) can be treated with a low-sodium (salt) diet and water pills. In severe cases the fluid may have to be drained. Sometimes surgery is required.

Pressure in the portal vein and collateral smaller veins - hypertension (high blood pressure) drugs are usually prescribed to control the increasing pressure in the blood vessels around the liver; the aim is to prevent severe bleeding. In some cases a stent may be surgically placed in the portal vein to hold it open. Signs of bleeding can be detected via an endoscopy.

Treatment of swollen varices - if the patient vomits blood or passes bloody stools they probably have esophageal varices (in the food pipe). Urgent medical attention is required. The following procedures may help:

• Banding - a small band is placed around the base of the varices to control bleeding. An endoscope goes down the patient's throat and esophagus during the procedure.
  
• Injection sclerotherapy - after an endoscopy a substance is injected into the varices which triggers a blood clot and scar tissue to form; this helps stem the bleeding.
  
• A Sengstaken tube with a balloon - the balloon is at the end of the tube. If endoscopy does not stop the bleeding a tube goes down the patient's throat and into their stomach. The balloon is inflated; this places pressure on the varices and stops the bleeding.
  
• TIPSS (transjugular intrahepatic portosystemic stent shunt) - if the above-mentioned therapies do not stem the bleeding, a stent (metal tube) is passed across the liver to join the portal and hepatic veins, creating a new route for the blood to flow through. This reduces pressure - pressure which was causing the varices.

Infections - the patient will be given antibiotics, and some other treatments.

Screening for liver cancer - patients with cirrhosis have a much higher risk of developing liver cancer. The doctor may recommend regular blood tests and imaging scans.

Hepatic encephalopathy (high blood toxin levels) - drugs can help treat excessive blood toxin levels. The signs and symptoms need to be explained to the patient so that they know what to look out for.

Liver transplant - if the cirrhosis is advanced and there is liver failure (liver does not function) the patient may need a liver transplant.

Prevention of cirrhosis

Alcohol - do not exceed the recommended daily/weekly alcohol limit.

• Men: maximum of 21 units per week, or three/four units per day
• Women: maximum of 14 units per week, or two/three units per day

Individuals who have cirrhosis should abstain from alcohol completely. Alcohol accelerates the progression of the disease.

Hepatitis B and C

• Use a condom when having sex
  
• Do not share needles when injecting drugs
  
• People at risk of becoming infected with hepatitis B, such as health care workers, social care workers, and police personnel can be vaccinated (there is currently no vaccine for hepatitis C)

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