Drugs, Diet, and the Liver
By: Howard J. Worman, MD

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       Introduction

      One of the most common causes of liver problems is drugs, of both
over-the-counter and prescription variety. These can affect the liver in
predictable and unpredictable ways. Many herbal or alternative remedies
taken for medicinal purposes can also cause liver damage. And although many
people believe otherwise, with the exception of alcohol, certain diets or
foods do not directly cause liver toxicity. However, obesity can lead to
liver problems.


      Drugs

      Drugs can have many different effects, causing hepatitis or
inflammation of the liver, cholestasis, or decreased bile flow within the
small bile ducts. Others may cause abnormal fat accumulation in the liver or
fatty liver (alcohol can also cause this). Then there are drugs that can
directly cause severe liver cell damage or cell death. Some cancer
chemotherapy drugs are responsible for the obstruction of veins in the
liver.

      The signs and symptoms of drug-induced liver disease can vary
tremendously. Often, they are only detected in laboratory test
abnormalities. The blood aminotransferase (ALT and AST) activities are
usually elevated in drug-related hepatitis. The blood alkaline phosphatase
and gamma-glutamyltranspetidase (GGT) activities are usually elevated in
cholestasis. The bottom line is that a detailed drug history is an essential
part of the evaluation of all patients with liver diseases, and doctors must
always consider drugs as a possible cause.

      Overdoses of certain drugs that are safe at therapeutic doses can
cause liver damage. For example, the over-the-counter prescription drug
acetaminophen (known as paracetamol in Europe) is used by millions of people
and extraordinarily safe at recommended doses. However, an overdose can
cause liver failure.

      Some drugs routinely affect the liver in a given percentage of
individuals. About ten percent of individuals treated with isoniazid, or
INH-which is used in the treatment and prevention of tuberculosis-develop
transient blood test abnormalities suggestive of liver disease. About one
percent of individuals develop severe hepatitis. The risk of hepatitis from
isoniazid increases with age. The statin class of drugs-used to lower serum
cholesterol concentrations-can also potentially cause liver damage.
Hepatitis, as presumed from increases in blood aminotransferase activities,
occurs in about one to two percent of patients who receive them.

      Certain individuals may have unpredictable or idiosyncratic reactions
to drugs. This can occur with normal doses of a generally safe drug. One
example is the liver toxicity caused by the anesthetic halothane. In cases
of idiosyncratic drug reactions, the goal is to identify the drug as the
cause of the liver disease, immediately stop it, and support the patient
until liver function recovers.

      Doctors should periodically perform blood tests to be on the lookout
for problems. If a drug is established to be the cause of liver disease, the
decision to stop or continue its use requires the judgment of an physician.
There is no substitute for the judgment of an experienced physician in
deciding if the risk of continuing a drug affecting the liver outweighs its
potential danger. A patient should also not stop taking a prescribed
medication without consulting a doctor. For example, mild drug-induced
cholestasis may be less significant than the repercussions of stopping a
medication to prevent seizures or psychosis. In contrast, continued use of a
particular drug to treat high blood pressure that is causing hepatitis is
probably not reasonable if equally effective alternatives are available.

      Different commonly used drugs can cause a variety of liver disorders.
Some include:

        a.. acetaminophen (when taken in overdose)
        b.. alpha-methyldopa (old blood pressure medication)
        c.. anabolic steroids (used by body builders)
        d.. anticonvulsants such as phenytoin and valproic acid
        e.. cancer chemotherapy
        f.. cardiovascular drugs (especially amiodarone)
        g.. estrogens (birth control pills)
        h.. halothane (anesthetic)
        i.. isoniazid (INH)
        j.. methotrexate (used to treat psoriasis and arthritis)
        k.. psychiatric medications (various ones)
        l.. statins (used to treat high cholesterol)

      Herbs

      Herbs or alternative medical therapies are gaining widespread
popularity in the U.S. Many people actually use herbal remedies in an
attempt to treat liver disease or strengthen the liver. Milk thistle, which
contains silymarin, is one of the most common. Users of herbal or
alternative therapies should realize that none have ever been shown to be
effective or up to the safety standards applied to drugs by the U.S. Food
and Drug Administration.

      Many so-called herbs are actually toxic to the liver. The wild
mushrooms known as death caps (Amatina phalloides) can cause fulminant
hepatic failure (catastrophic liver failure) or even death. Jamaican bush
teas, often used locally for medicinal purposes, contain pyrrolizidine
alkaloids that cause veno-occlusive disease of the liver. This disease is
characterized by obstruction of the small veins that drain the liver. A
similar condition is caused by some forms of high-dose cancer chemotherapy.


      Diet

      There is really no such thing as a "healthy-liver diet." There are no
foods, assuming you don't consume toxins or contaminated foods, that
directly cause liver disease. One obvious exception is ethyl alcohol, if you
consider it a food. Perhaps the only notable cause of liver damage caused by
eating foods is contamination by aflatoxins. Although virtually nonexistent
in the developed world, aflatoxins are a common cause of chronic liver
disease in some areas, especially tropical regions. They are produced by a
mold that contaminates a variety of nuts (commonly peanuts), beans, and
grains. Chronic aflatoxin ingestion can cause cirrhosis and primary liver
cancer.

      If there is a healthy liver diet, it would be a general good-health
diet. Such a diet is low in fat and of reasonable caloric intake. Regular
exercise is also important and alcohol should only be used in moderation.
One liver disease that can indirectly result from diet is fatty liver of
obesity, which is abnormal fatty infiltration of the liver in overweight
individuals. If severe, fatty liver can lead to a condition known as
nonalcoholic steatohepatitis or NASH, which can progress to cirrhosis. Fatty
liver or NASH can also be seen in patients with diabetes and rarely in
non-obese individuals (for unclear reasons). Fatty liver can also be caused
by excessive alcohol intake and, when examining a liver biopsy under the
microscope, NASH looks identical to alcoholic hepatitis.

      In other words, being overweight or having diabetes can lead to liver
disease that in many ways resembles the effects of excessive alcohol
consumption.

      Chronic-liver-disease diet
      What about diet for the patient with chronic liver disease? Alcohol is
a contentious subject in this regard. For example, how much alcohol can a
person who has liver disease caused by hepatitis C drink? There is no
generally agreed upon answer to this question, although most doctors
probably would recommend that two drinks a day would be the absolute
maximum. Some doctors are adamant that people with liver disease should not
drink any alcohol at all.

       Besides eliminating alcohol consumption and maintaining an ideal body
weight by eating right and exercising, there are no special foods that
should be avoided or consumed. A generally healthy diet as recommended to
all individuals is appropriate for most patients with liver diseases.

      However, an exception to this rule is the patient with cirrhosis.
Patients with cirrhosis tend to retain salt and water which, in advanced
cases, can cause edema (swelling) and ascites (severe accumulation of fluid
in the abdomen). Patients with cirrhosis should therefore be on a low-salt
diet and those with advanced cirrhosis should consume virtually no salt. In
subjects with advanced cirrhosis and confusion caused by hepatic
encephalopathy, it may also be necessary to restrict protein intake.
Patients with cirrhosis should consult a doctor or registered dietitian
regarding an appropriate low-salt or low-protein diet.


      Conclusion

      Many over-the-counter and prescription drugs can cause liver problems
ranging from minor to very serious. Doctors and patients should always be
aware that medications may be contributing to abnormal liver blood test
results. Many herbal and alternative medications may also cause liver
disease, and patients who ingest these types of medications should realize
that there may be serious risks. Overweight patients are at risk for fatty
liver, which can often be avoided by maintaining an ideal body weight with a
healthy diet and exercise. Patients with chronic liver diseases should also
maintain a generally healthy diet; there are no special foods that should be
consumed or avoided other than those recommended for the general population.
An exception is cirrhosis, in which case salt may have to be restricted.
Individuals with liver disease caused by alcohol should never consume
alcohol. Those with nonalcoholic liver disease may be able to consume
reasonable, limited quantities of alcohol.