Drinking and the Liver

Alcohol Alert

National Institute on Alcohol Abuse and Alcoholism

No. 19 PH 329 January 1993


Alcohol and the Liver

Alcoholic liver disease is one of the most serious medical
consequences of chronic alcohol use. Moreover, chronic excessive alcohol
use is the single most important cause of illness and death from liver
disease (alcoholic hepatitis and cirrhosis) in the United States (1).

The Normal Liver

Normal liver function is essential to life. The liver is the largest
organ of the body, located in the upper right section of the abdomen. It
filters circulating blood, removing and destroying toxic substances; it
secretes bile into the small intestine to help digest and absorb fats;
and it is involved in many of the metabolic systems of the body. Digested
food substances are carried from the intestine directly to the liver for
further processing. The liver stores vitamins; synthesizes cholesterol;
metabolizes or stores sugars; processes fats; and assembles amino acids
into various proteins, some for use within the liver and some for export.
The liver controls blood fluidity and regulates blood-clotting
mechanisms. It also converts the products of protein metabolism into urea
for excretion by the kidneys.

Alcoholic Liver Disease

The three alcohol-induced liver conditions are fatty liver, alcoholic
hepatitis, and cirrhosis.

Some degree of fat deposition usually occurs in the liver after
short-term excessive use of alcohol. However, fatty liver rarely causes
illness (2).

In some heavy drinkers, alcohol consumption leads to severe alcoholic
hepatitis, an inflammation of the liver characterized by fever, jaundice,
and abdominal pain (3). Severe alcoholic hepatitis can be confused with
many serious abdominal conditions, such as cholecystitis (inflammation of
the gall bladder), appendicitis, and pancreatitis. It is important to be
aware of this potential confusion because some of these other conditions
require surgery, and surgery is contraindicated in patients with
alcoholic hepatitis. These patients have a high death rate following

The most advanced form of alcoholic liver injury is alcoholic
cirrhosis. This condition is marked by progressive development of scar
tissue that chokes off blood vessels and distorts the normal architecture
of the liver (2).

A patient may have only one of the three alcohol-induced conditions or
any combination of them. Traditionally, they have been considered
sequentially related, progressing from fatty liver to alcoholic hepatitis
to cirrhosis. However, some studies have demonstrated that alcoholics may
progress to cirrhosis without passing through any visible stage
resembling hepatitis. Thus, alcoholic cirrhosis can appear insidiously,
with little warning (4).

Fatty liver is reversible with abstinence. Alcoholic hepatitis may be
fatal but can be reversible with abstinence (5). While alcoholic
cirrhosis is often progressive and fatal, it can stabilize with
abstinence (3).

Complications of advanced liver disease include severe bleeding from
distended veins in the esophagus, brain disorders (hepatic
encephalopathy), accumulation of fluid in the abdomen (ascites), and
kidney failure (6).

Not all liver disease that may occur in alcoholics is caused by
alcohol. In addition, when alcohol-induced liver disease does occur, it
may be accompanied by other conditions, not related to alcohol, that also
can cause liver failure. These include nonalcoholic hepatitis and
exposure to drugs and occupational chemicals (see below).

Extent of the Problem

Alcohol-related cirrhosis is know n to be underreported. However,
about 44 percent of all deaths caused by cirrhosis in North America are
reportedly alcohol related (7).

Up to 100 percent of heavy drinkers show evidence of fatty liver, an
estimated 10 to 35 percent develop alcoholic hepatitis, and 10 to 20
percent develop cirrhosis (1).

Daily drinkers are at a higher risk of developing alcoholic cirrhosis
than are binge drinkers (8). In general, patients with alcoholic
cirrhosis have been drinking heavily for 10 to 20 years (8-10).

Mortality from cirrhosis in the United States varies significantly
with gender, race, and age. In 1988, the highest mortality from cirrhosis
occurred in nonwhite males, followed by white males, nonwhite females,
and white females (11). Most of the deaths from alcoholic cirrhosis occur
in people ages 40-65 (11). Thus, alcoholic cirrhosis kills people in what
should be their most productive years.

How Does Alcohol Damage the Liver?

Currently we do not know how alcohol causes cirrhosis. However, there
are many mechanisms by which alcohol injures the liver. Many of these
mechanisms are poorly understood, in part because no simple animal model
has been developed for cirrhosis. In addition, there is considerable
variation among individuals in susceptibility to alcoholic liver disease,
so that among people drinking similar amounts, only some develop

Diet. Before the 1970’s, alcoholic cirrhosis
was believed to arise from nutritional deficiencies common among heavy
drinkers. Overwhelming evidence subsequently proved that alcohol itself
is toxic to the liver, even when nutrition is adequate. Today, it is
believed that nutritional effects and direct alcohol toxicity interact in
such complex ways that the influence of the two cannot be separated

Genetics. Genetic differences might explain
why some heavy drinkers develop cirrhosis while others do not. The scar
tissue that forms in the cirrhotic liver is composed of the protein
collagen. It has been suggested that stimulation of collagen synthesis
resulting from activation of the collagen gene may promote liver scarring
(13). In that case, it might be speculated that differences in genes for
collagen among individual drinkers may be associated with differences in
the development of alcoholic cirrhosis.

Free radicals and acetaldehyde. Much of the
cell damage that occurs during liver degeneration is believed to be
caused by free radicals, highly reactive molecular fragments, liberated
during alcohol metabolism. The damage caused by free radicals can include
the destruction of essential components of cell membranes. The cell’s
natural defenses against free radicals include the natural chemicals
glutathione (GSH) and vitamin E.

The function of GSH and vitamin E is impaired in alcoholics. For
example, chronic alcohol ingestion decreased GSH levels in baboons and
humans (14). Similarly, chronic alcohol feeding significantly increased
damage caused by free radicals in liver cells of rats maintained on a
diet low in vitamin E (15).

Acetaldehyde, the primary metabolic product of alcohol in the liver,
appears to be a key generator of free radicals. Because of its
reactivity, acetaldehyde can promote membrane damage and can stimulate
the synthesis of collagen to form scar tissue (16-18).

Nonalcoholic hepatitis. The increased
prevalence of hepatitis C viral infection in alcoholics might explain
some of the variation in individual susceptibility to alcoholic liver
disease (19). In addition, chronic hepatitis C infection is significantly
correlated with the severity of alcoholic cirrhosis (20) and may
influence the progression of alcoholic liver disease in some patients

The immune system. The immune system
responds or contributes to liver cell damage in alcohol-induced liver
disease in complex ways, although a causal relationship is unclear.
Acetaldehyde has been shown to attach chemically to liver proteins. The
altered proteins may then trigger various immune responses (23). Cellular
toxins are released, causing cell damage; certain proteins are deposited
along the liver’s small blood-carrying channels; and specific white blood
cells are activated (24-27).

Liver metabolism. Chronic alcohol
administration has been found to increase the rate of oxygen metabolism
by the liver. In addition, a series of studies by Israel and colleagues
(28) demonstrated similarities in the effects of alcohol and thyroid
hormone on liver cells. They called these effects the “liver
hypermetabolic state.” As a result of these studies, propylthio-uracil, a
drug used to treat excessive production of thyroid hormone, has been
tested for the treatment of alcoholic liver disease (see Treatment

Gender. Current evidence suggests that women
may be more susceptible than men to alcoholic liver disease; more
research is necessary to validate this hypothesis (8,19).

Environmental factors. Chronic alcohol
consumption markedly increases the liver toxicity of various industrial
solvents, anesthetics, medications, and vitamins (29,30). For example,
acetaminophen (Tylenol and others), a widely used over-the-counter pain
reliever, is generally safe when taken in recommended doses. However,
excessive use of acetaminophen has been associated with liver toxicity in
people drinking heavily (30-32). Alcohol also enhances the toxicity of
excess vitamin A, so care must be taken when treating an alcoholic with a
vitamin A deficiency (33).


Alcoholic hepatitis. Mortality from
alcoholic hepatitis during the early weeks of treatment is very high.
Although the evidence is inconsistent, corticosteroid therapy may improve
survival during the early stages of the disease in patients with severe
alcoholic hepatitis (34-38). Supplemental amino acids may improve a
patient’s nutrition but not the chances of survival or progression to
cirrhosis (39).

Orrego and colleagues (40) reported that the drug propylthiouracil
(PTU) improved survival of patients with all types of alcoholic liver
disease. However, other studies have demonstrated no benefit from this
therapy in patients with alcoholic hepatitis (41,42).

Abstinence is the cornerstone of therapy for patients with prolonged
alcoholic hepatitis. Also important are careful control of diet with
correction of vitamin deficiencies, and management of medical
complications (38).

If the patient with alcoholic hepatitis lives to leave the hospital,
abstinence is essential for long-term survival. Alexander and coworkers
(43) found that more than 80 percent of those who abstained or markedly
reduced their drinking were alive 7 years later, whereas only 50 percent
who continued to drink were alive 7 years later.

Alcoholic cirrhosis. Treatment for cirrhosis
is directed at symptoms and complications, with abstinence a requirement.
For terminally ill patients, liver transplantation is the only effective
treatment. This procedure in alcoholic cirrhotic patients has
demonstrated success and survival rates equal to those for nonalcoholic
cirrhotic patients (44).

Future directions in cirrhosis therapy are suggested by a study
showing that lecithin protects against the development of alcohol-induced
liver scarring in baboons (45). This therapy has not yet been studied in


Alcohol and the Liver–A Commentary by
NIAAA Director Enoch Gordis, M.D.

Abstinence from alcohol is the single most important component of
treatmen t for alcoholic liver disease. Continued drinking will worsen
the condition of patients with this disease and greatly increase their
risk for death. Physicians who treat alcoholic liver disease, no matter
how competently, and who do not address their patients’ drinking are
practicing bad medicine, akin to treating an iron-deficiency anemia and
disregarding the colon cancer that is causing it.

Because many alcohol abusers and most alcoholics require some form of
treatment to remain abstinent, simply giving advice to “quit” drinking
often is not sufficient. Physicians who choose not to manage their
patients’ alcohol problems may refer these patients to specialized
alcohol treatment providers for evaluation and appropriate treatment. In
referring a patient to appropriate alcohol treatment, physicians should
keep informed of their patients’ progress, as relapse may further
complicate management of the alcoholic liver disease.


ACKNOWLEDGMENT: The National Institute on Alcohol Abuse and Alcoholism
wishes to acknowledge the valuable contributions of Marcus A. Rothschild,
M.D., editor of Alcohol: Clinical and Experimental Research, to
the development of this Alcohol Alert.


All material contained in the Alcohol Alert is in the public
domain and may be used or reproduced without permission from NIAAA.
Citation of the source is appreciated.

Copies of the Alcohol Alert are available free of charge from
the Scientific Communications Branch, Office of Scientific Affairs,
NIAAA, 5600 Fishers Lane, Room 16C-14, Rockville, MD 20857. Telephone:



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