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Alcoholic liver disease (ALD), also called alcohol-related liver disease (ARLD), is a term that encompasses the liver manifestations of alcohol overconsumption, including fatty liver, alcoholic hepatitis, and chronic hepatitis with liver fibrosis or cirrhosis.
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It is the major cause of liver disease in Western countries, and is the leading cause of death from excessive drinking. Although steatosis (fatty liver disease) 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.
For patients with chronic hepatitis B, a strict adherence to abstinence from alcohol is highly recommended.
Presentation
Risk factors
As of 2010, known risk factors of ALD are:
- Quantity of alcohol taken: Consumption of 60–80 g per day (14 g is considered one standard drink in the US, e.g. hard liquor, wine, beer; drinking a six-pack of 5% ABV beer daily would be 84 g and just over the upper limit) for 20 years or more in men, or 20 g/day for women significantly increases the risk of hepatitis and fibrosis by 6% to 41%.
- Pattern of drinking: Drinking outside of meal times increases up to 3 times the risk of alcoholic liver disease.
- Sex: 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 alcohol absorption due to the menstrual cycle may explain this phenomenon.
Fatty change
Fatty change, or steatosis, is the accumulation of fatty acids in liver cells. This can be seen as fatty globules under the microscope. Alcoholism causes development of large fatty globules (macro-vesicular steatosis) throughout the liver and can begin to occur after a few days of heavy drinking. Alcohol is metabolized by alcohol dehydrogenase (ADH) into acetaldehyde, then further metabolized by aldehyde dehydrogenase (ALDH) into acetic acid, which is finally oxidized into carbon dioxide () and water (). This process generates NADH, and increases the NADH/NAD+ ratio. A higher NADH concentration induces fatty acid synthesis while a decreased NAD level results in decreased fatty acid oxidation. Subsequently, the higher levels of fatty acids signal the liver cells to compound it to glycerol to form triglycerides. These triglycerides accumulate, resulting in fatty liver.
Alcoholic hepatitis
Alcoholic hepatitis is characterized by the inflammation of hepatocytes. Between 10% and 35% of heavy drinkers develop alcoholic hepatitis (NIAAA, 1993). 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 steato-necrosis and the inflammation appears to predispose to liver fibrosis. Inflammatory cytokines (TNF-alpha, IL-6 and IL-8) are thought to be essential in the initiation and perpetuation of liver injury and cytotoxic hepatomegaly by inducing apoptosis and severe hepatotoxicity. One possible mechanism for the increased activity of TNF-α is the increased intestinal permeability due to liver disease. This facilitates the absorption of the gut-produced endotoxin into the portal circulation. The Kupffer cells of the liver then phagocytose endotoxin, stimulating the release of TNF-α. TNF-α then triggers apoptotic pathways through the activation of caspases, resulting in cell death. Between 10% and 20% of heavy drinkers will develop cirrhosis of the liver (NIAAA, 1993). Acetaldehyde may be responsible for alcohol-induced fibrosis by stimulating collagen deposition by hepatic stellate cells.
Laboratory findings
In people with alcoholic hepatitis, the serum aspartate aminotransferase (AST) to alanine aminotransferase (ALT) ratio is greater than 2:1. AST and ALT levels are almost always less than 500. The elevated AST to ALT ratio is due to deficiency of pyridoxal phosphate, which is required in the ALT enzyme synthetic pathway. Furthermore, alcohol metabolite–induced injury of hepatic mitochondria results in AST isoenzyme release. Other laboratory findings include red blood cell macrocytosis (mean corpuscular volume > 100) and elevations of serum gamma-glutamyl transferase (GGT), alkaline phosphatase, and bilirubin levels. Folate level is reduced in alcoholic patients due to decreased intestinal absorption, increased bone marrow requirement for folate in the presence of alcohol, and increased urinary loss. The magnitude of leukocytopenia (white blood cell depletion) reflects severity of liver injury. Histologic features include Mallory bodies, giant mitochondria, hepatocyte necrosis, and neutrophil infiltration in the area around the veins. Mallory bodies, which are also present in other liver diseases, are condensations of cytokeratin components in the hepatocyte cytoplasm and do not contribute to liver injury. Up to 70% of patients with moderate to severe alcoholic hepatitis already have cirrhosis identifiable on biopsy examination at the time of diagnosis.
Treatment
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. Corticosteroids are sometimes used; however, this is recommended only when severe liver inflammation is present. One review claimed benefit for S-adenosyl methionine in disease models.
The effects of anti-tumor necrosis factor medications 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.
Transplantation
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 non-ALD. The requirements for transplant listing vary among transplant centers. A period of alcohol abstinence for at least 6 months is often used prior to liver transplant. Sustained sobriety may improve liver function enough to avoid transplantation and allows clinicians to assess patient adherence to treatment, however there is neither a consensus nor absolute requirement on timing. Additionally the duration of abstinence prior to transplantation has not been proven to be related to the risk of recidivism. This suggests the risk of relapse may be more related to psychosocial factors which can be carefully evaluated before transplantation by a team of mental health providers and social workers. 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.
Prognosis
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 30-day (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 experience a 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. Alcoholic liver disease can lead to the development of exocrine pancreatic insufficiency.