Alcoholic liver disease is a term that encompasses the liver manifestations of alcohol overconsumption, including fatty liver, alcoholic hepatitis, and chronic hepatitis with liver fibrosis or cirrhosis.
It is the major cause of liver disease in Western countries. Although steatosis (fatty liver) will develop in any individual who consumes a large quantity of alcoholic beverages over a long period of time, this process is transient and reversible. Of all chronic heavy drinkers, only 15–20% develop hepatitis or cirrhosis, which can occur concomitantly or in succession.
How alcohol damages the liver is not completely understood. 80% of alcohol passes through the liver to be detoxified. Chronic consumption of alcohol results in the secretion of pro-inflammatory cytokines (TNF-alpha, Interleukin 6 [IL6] and Interleukin 8 [IL8]), oxidative stress, lipid peroxidation, and acetaldehyde toxicity. These factors cause inflammation, apoptosis and eventually fibrosis of liver cells. Why this occurs in only a few individuals is still unclear. Additionally, the liver has tremendous capacity to regenerate and even when 75% of hepatocytes are dead, it continues to function as normal.
The risk factors presently known are:
- Quantity of alcohol taken: Consumption of 60–80g per day (about 75–100 ml/day) for 20 years or more in men, or 20g/day (about 25 ml/day) for women significantly increases the risk of hepatitis and fibrosis by 7 to 47%,
- Pattern of drinking: Drinking outside of meal times increases up to 3 times the risk of alcoholic liver disease.
- Gender: Women are twice as susceptible to alcohol-related liver disease, and may develop alcoholic liver disease with shorter durations and doses of chronic consumption. The lesser amount of alcohol dehydrogenase secreted in the gut, higher proportion of body fat in women, and changes in fat absorption due to the menstrual cycle may explain this phenomenon.
- Hepatitis C infection: A concomitant hepatitis C infection significantly accelerates the process of liver injury.
- Genetic factors: Genetic factors predispose both to alcoholism and to alcoholic liver disease. Both monozygotic twins are more likely to be alcoholics and to develop liver cirrhosis than both dizygotic twins. Polymorphisms in the enzymes involved in the metabolism of alcohol, such as ADH, ALDH, CYP4502E1, mitochondrial dysfunction, and cytokine polymorphism may partly explain this genetic component. However, no specific polymorphisms have currently been firmly linked to alcoholic liver disease.
- Iron overload (Hemochromatosis)
- Diet: Malnutrition, particularly vitamin A and E deficiencies, can worsen alcohol-induced liver damage by preventing regeneration of hepatocytes. This is particularly a concern as alcoholics are usually malnourished because of a poor diet, anorexia, and encephalopathy.
Not drinking further alcohol is the most important part of treatment. People with chronic HCV infection should abstain from any alcohol intake, due to the risk for rapid acceleration of liver disease.
A 2006 Cochrane review did not find evidence sufficient for the use of corticosteroids. They are sometimes; however, recommended when severe liver inflammation is present.
The effects of anti–tumor necrosis factor medication such as infliximab and etanercept are unclear and possibly harmful. Evidence is unclear for pentoxifylline. Propylthiouracil may result in harm.
Evidence does not support supplemental nutrition in liver disease.
Although in rare cases liver cirrhosis is reversible,the disease process remains mostly irreversible. Liver transplantation remains the only definitive therapy.Today,survival after liver transplantation is similar for people with ALD and nonALD. The requirements for transplant listing are the same as those for other types of liver disease, except for a 6-month sobriety prerequisite along with psychiatric evaluation and rehabilitation assistance (i.e., Alcoholics Anonymous). Specific requirements vary among the transplant centers. Relapse to alcohol use after transplant listing results in delisting. Re-listing is possible in many institutions, but only after 3–6 months of sobriety. There are limited data on transplant survival in patients transplanted for acute alcoholic hepatitis,but it is believed to be similar to that in nonacute ALD, non-ALD, and alcoholic hepatitis with MDF less than 32.
Alcohol-induced liver damage occurs via generation of oxidants. Thus alternative health care practitioners often recommend natural antioxidant supplements like milk thistle. Currently, there exists no substantive clinical evidence to suggest that milk thistle or other antioxidant supplements are efficacious beyond placebo in treating liver disease caused by chronic alcohol consumption. One review claimed benefit for S-adenosyl methionine in disease models.There however is insufficient human evidence.
The prognosis for people with ALD depends on the liver histology as well as cofactors, such as concomitant chronic viral hepatitis.Among patients with alcoholic hepatitis, progression to liver cirrhosis occurs at 10–20% per year, and 70% will eventually develop cirrhosis. Despite cessation of alcohol use, only 10% will have normalization of histology and serum liver enzyme levels. As previously noted, the MDF has been used to predict short-term mortality (i.e., MDF ≥ 32 associated with spontaneous survival of 50–65% without corticosteroid therapy, and MDF < 32 associated with spontaneous survival of 90%).The Model for End-Stage Liver Disease (MELD) score has also been found to have similar predictive accuracy in 30day (MELD > 11) and 90-day (MELD > 21) mortality. Liver cirrhosis develops in 6–14% of those who consume more than 60–80 g of alcohol daily for men and more than 20 g daily for women. Even in those who drink more than 120 g daily, only 13.5% will suffer serious alcohol-related liver injury. Nevertheless, alcohol-related mortality was the third leading cause of death in 2003 in the United States. Worldwide mortality is estimated to be 150,000 per year.