Alcoholic liver disease

Alcoholic liver disease is the major cause of liver disease in Western countries, (in Asian countries, viral hepatitis is the major cause). It arises from the excessive ingestion of alcohol. Even though millions of individuals drink alcohol on a regular basis, only a few heavy drinkers develop liver damage. How alcohol damages the liver is not completely understood. It is known that alcohol produces toxic chemicals like acetaldehyde which can damage liver cells, but why this occurs in only a few individuals is still in debate. When alcohol damages the liver, the function of the organ is not immediately compromised as the liver has a tremendous capacity to regenerate and even when 75% of the liver is damaged, it continues to function as normal. When alcohol is consumed for a long time, it eventually results in liver scarring or what is known as cirrhosis or end-stage alcoholic liver disease.

Risk factors
The risk factors presently known are: quantity of alcohol taken, type of alcohol (beer and spirits have increased risk), gender (females are twice as susceptible to alcohol related liver disease, presently explained by the difference in the ability to metabolize it), hepatitis C infection, genetic factors (changes in the profiles of various enzymes involved in the metabolism of alcohol, such as ADH, ALDH, CYP4502E1, mitochondrial dysfunction, and cytokine polymorphism) and malnutrition and diet (particularly vitamin A and E deficiencies). Generally it is believed that certain genes increase metabolism of alcohol, which may increase risk of cirrhosis and even alcohol related cancers. Alcohol-induced liver injury can be worsened by hepatitis. If one has hepatitis B or hepatitis C and consumes alcohol, cirrhosis occurs sooner. Alcohol-induced liver disease is also worsened in people who have iron overload. Malnutrition can worsen alcohol-induced liver damage. Most alcoholics tend to eat poorly and often substitute alcohol as a meal. The liver has a great capacity to regenerate, but without proper nutrition, it quickly fails.

Fatty change
Fatty change, or steatosis is the accumulation of fatty acids in liver cells which can be seen as fatty globules under the microscope. Alcoholism causes development of large fatty globules (macrovesicular steatosis) throughout the liver and can begin to occur after a few days of heavy drinking, (Dr.Darryl S. Inaba, Pharm D, and William E. Cohen, 2004) Development of Macrovesicular steatosis, small fatty acid globules may have different causes, such as diabetes, obesity and starvation. The mechanism of action in alcohol induced fatty liver involves an above average NADH:NAD ratio caused by the heavy demands of alcohol metabolism, including other damaging metabolites such as free radicals and acetaldehyde that are very toxic, (Higuchi, Kato, Miura, & Ishi, 1996) Alcohol is metabolized by alcohol dehydrogenase (ADH)into highly toxic acetaldehyde, then further metabolized by aldehyde dehydrogenase (ALDH) into acetic acid which is oxidized into Carbon Dioxide (CO2) and water (H2O). (Darryl S. Inaba, Pharm. D, and William E. Cohen, 2004:185) A higher NADH concentration induces fatty acid synthesis (creation) while a decreased NAD level results in decreased fatty acid oxidation (processing). Consequently, the higher levels of fatty acids signal the hepatocytes (liver cells) to compound it to glycerol to form triglycerides.

Alcoholic hepatitis
Between 10% and 35% of heavy drinkers develop alcoholic hepatitis, (NIAAA, 1993). Acute hepatitis or inflammatory reaction of cells affected by fatty change. While development of hepatitis is not directly related to the dose of alcohol, some people seem more prone to this reaction than others. This is called alcoholic steatonecrosis and the inflammation appears to predispose to liver fibrosis.

Cirrhosis
Between 10% to 20% of heavy drinkers will develop Cirrhosis of the liver.(NIAAA, 1993) Cirrhosis is a late stage of serious liver disease marked by inflammation (swelling), fibrosis (cellular hardening) and damaged membranes preventing detoxification of chemicals in the body, ending in scarring and necrosis (cell death.) Symptoms include jaundice (yellowing), liver enlargement, and pain and tenderness from the structural changes in damaged liver architecture. It is progressive and without total abstinence from alcohol use, (80% of alcohol passes through the liver to be detoxified) will eventually lead to liver failure. Late complications of cirrhosis or liver failure include portal hypertension (high blood pressure related to kidney problems), coagulation disorders blood clotting is impaired, ascites (heavy abdominal swelling due to build up of fluids in the tissues) and other complications, including hepatic encephalopathy and the hepatorenal syndrome.

Cirrhosis can also result from other causes than alcohol abuse, such as viral hepatitis and heavy exposure to toxins other than alcohol. The late stages of cirrhosis may look similar medically, regardless of cause. This phenomenon is termed the "final common pathway" for the disease.

Fatty change and alcoholic hepatitis with abstinence can be reversible. The later stages of fibrosis and cirrhosis tend to be irreversible, but can usually be contained with abstinence for long periods of time.

Diagnosis
There are many tests to assess alcoholic liver damage. Besides blood examination, doctors use ultrasound and a CT scan to assess liver damage. In some cases a liver biopsy is performed. This minor procedure is done under local anesthesia, and involves placing a small needle in the liver and obtaining a piece of tissue. The tissue is then sent to the laboratory to be examined under a microscope.

Treatment
The first treatment of alcohol-induced liver disease is cessation of alcohol consumption. This is the only way to reverse liver damage or prevent liver injury from worsening. Without treatment, most patients with alcohol-induced liver damage will develop liver cirrhosis. Other treatment for alcoholic hepatitis include:

Nutrition
Doctors recommend a calorie-rich diet to help the liver in its regeneration process. Dietary fat must be reduced because fat interferes with alcohol metabolism. The diet is usually supplemented with vitamins and dietary minerals (including calcium and iron).

Many nutritionists recommend a diet high in protein, with frequent small meals eaten during the day, about 5-6 instead of the usual 3. Nutritionally, supporting the liver and supplementing with nutrients that enhance liver function is recommended. These include carnitine, which will help reverse fatty livers, and vitamin C, which is an antioxidant, aids in collagen synthesis, and increases the production of neurotransmitters such as norepinephrine and serotonin, as well as supplementing with the nutrients that have been depleted due to the alcohol consumption. Eliminating any food that may be manifesting as an intolerance and alkalizing the body is also important. There are some supplements that are recommended to help reduce cravings for alcohol, including choline, glutamine, and vitamin C. As research shows glucose increases the toxicity of centrilobular hepatotoxicants by inhibiting cell division and repair, it is suggested fatty acids are used by the liver instead of glucose as a fuel source to aid in repair; thus, it is recommended the patient consumes a diet high in protein and essential fatty acids, e.g. omega 3. Cessation of alcohol consumption and cigarette smoking, and increasing exercise are lifestyle recommendations to decrease the risk of liver disease caused by alcoholic stress.

Drugs
Abstinence from alcohol intake and nutritional modification form the backbone in the management of ALD. Symptom treatment can include: corticosteroids for severe cases, anticytokines (infliximab and pentoxifylline), propylthiouracil to modify metabolism and colchicine to inhibit hepatic fibrosis.

Antioxidants
It is widely believed that alcohol-induced liver damage occurs via generation of oxidants. Thus alternative health care practitioners routinely recommend natural antioxidant supplements like milk thistle. Unfortunately, there is no valid clinical data to show that milk thistle truly works. Rambaldi A, Jacobs BP, Iaquinto G, Gluud C (2005). "Milk thistle for alcoholic and/or hepatitis B or C liver diseases--a systematic cochrane hepato-biliary group review with meta-analyses of randomized clinical trials". Am. J. Gastroenterol. 100 (11): 2583–91. doi:10.1111/j.1572-0241.2005.00262.x. PMID 16279916

Transplant
When all else fails and the liver is severely damaged, the only alternative is a liver transplant. While this is a viable option, liver transplant donors are scarce and usually there is a long waiting list in any given hospital. One of the criteria to become eligible for a liver transplant is to discontinue alcohol consumption for a minimum of six months.

Complications and prognosis
As the liver scars, the blood vessels become noncompliant and narrow. This leads to increased pressure in blood vessels entering the liver. Over time, this causes a backlog of blood (portal hypertension), and is associated with massive bleeding. Enlarged veins also develop to bypass the blockages in the liver. These veins are very fragile and have a tendency to rupture and bleed (varices). Variceal bleeding can be life-threatening and needs emergency treatment. Once the liver is damaged, fluid builds up in the abdomen and legs. The fluid buildup presses on the diaphragm and can make breathing very difficult. As liver damage progresses, the liver is unable to get rid of pigments like bilirubin and both the skin and eyes turn yellow (jaundice). The dark pigment also causes the urine to appear dark; however, the stools appear pale. Also with the progression of the disease, the liver can release toxic substances (including ammonia) which then lead to brain damage. This results in altered mental state, and may cause behavior and personality changes.