Drugs, Diet, and the Liver

liver411

By: Howard J. Worman, MD


       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 onalcoholic liver disease may be able to consume reasonable, limited quantities of alcohol.