The liver is responsible for detoxifying most drugs and toxins and eliminating them from the body. In the process, some of these toxins can damage the liver—a condition called hepatotoxicity. Common culprits include alcohol, illicit drugs, medications, herbs, and dietary supplements.
Drug– or alcohol–related hepatotoxicity is the most common cause of liver failure. Alcohol–related liver disease alone accounts for more than 12,000 deaths yearly in the United States, and alcohol abuse is the most common cause of cirrhosis.
Alcohol is the most frequently abused drug worldwide. Abuse results in a broad spectrum of liver disease, which can result in cirrhosis and end–stage liver failure requiring transplantation. The damage may be silent for years. Many alcoholics become symptomatic only when severe, life–threatening liver disease is already present.
Virtually any drug can cause some degree of liver damage, although certain drugs are more toxic than others. Common hepatotoxic substances include acetaminophen (Tylenol), aspirin, various antibiotics (e.g., tetracycline and isoniazid), and cholesterol–lowering drugs (“statins”). In high doses, vitamin A, arsenic, iron, and copper can be hepatotoxic. Further, hepatotoxicity may be the most common adverse effect of herbal supplements. Herbs with known potential for toxicity include kava, pennyroyal oil, ma–huang (ephedra), valerian, mistletoe, comfrey, chaparral, sassafras, borage, and germander.
The severity of liver disease varies greatly from person to person. Some people remain asymptomatic despite significant liver damage, while others have symptoms of a severe, acute illness. Nausea, vomiting, malaise, and profuse sweating are common symptoms. A syndrome similar to viral hepatitis may occur, including fever, headache, jaundice (a yellow discoloration of the skin), and right–sided abdominal pain.
Because of the liver’s regenerative ability, withdrawal of or abstinence from offending substances can result in significant reversal of liver damage, even in cases of advanced disease.
Risk Factors
- Gender: Females who drink alcohol have an increased risk of liver disease compared with men, and liver disease in women tends to progress more rapidly than in men.
- Genetics: There appear to be genetic predispositions to alcohol abuse and alcoholic liver disease. However, specific genes have yet to be identified.
- Viral hepatitis: Infection with hepatitis B virus or hepatitis C virus is strongly associated with risk of advanced liver disease in alcoholic individuals.
- Obesity
- Malnutrition. Inadequate nutritional intake in chronic alcohol abusers may worsen the severity of liver disease.
- Asian race: Many Asians have a relative deficiency of an enzyme that results in flushing upon alcohol intake, which may create an aversion to alcohol use.
- Acetaminophen: The combination of alcohol and acetaminophen (Tylenol) should be strictly avoided because they can both be toxic to the liver.
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Alcoholic and Toxic Liver Disease: Diagnosis and Treatment
Diagnosis - The diagnosis of drug– and toxin–induced liver injury is often difficult. A detailed history and physical examination are essential, and the physician should investigate the possibility of accidental, environmental, and intentional exposures.
In suspected cases of alcoholism, a careful history and the “CAGE criteria” may be used to establish the diagnosis of alcoholism. A positive response to at least two questions is seen in the majority of people with alcoholism. - Have you felt the need to Cut down drinking?
- Have you ever felt Annoyed by criticism of drinking?
- Have you had Guilty feelings about drinking?
- Do you ever take a morning Eye opener?
- Blood testing is often the most important aspect of diagnosis. Blood tests are used to evaluate liver function and nutritional status, assess coexisting disease, and screen for toxins and drugs.
- In some cases, a biopsy may be necessary to identify liver damage and evaluate for various liver diseases, including cancer and cirrhosis.
- Ultrasound, abdominal x–ray, CT scan, or MRI may be indicated to further evaluate the liver and rule out other abdominal disorders.
Treatment - Suspected drugs or toxins should be immediately stopped. Recovery often occurs after withdrawal of the offending substance.
- Abstinence from alcohol is essential, even when alcohol was not the cause of damage. It can aggravate the damage caused by other substances. Individuals with alcohol problems should seek counseling on alcohol cessation, including referral to Alcoholics Anonymous, psychotherapy, or similar programs.
- Weight reduction is a requirement for overweight persons.
- Acetaminophen overdose is a medical emergency treated with activated charcoal and n–acetylcysteine.
- Other than treatment for acute acetaminophen toxicity, specific therapies are generally not available. In cases of allergic reactions to medications (e.g., penicillin) or alcoholic hepatitis, corticosteroids may be useful.
- Supportive treatments in cases of liver failure include nutritional changes (see Nutritional Considerations), vitamin K supplementation to improve coagulation, and correction of micronutrient deficiencies (e.g., folate supplementation).
- Liver transplantation may be required in patients with severe acute liver failure or chronic liver disease.
Alcoholic and Toxic Liver Disease: Nutritional Considerations - Vitamins and supplements with potential or suspected hepatotoxicity should be avoided.
In particular, high doses of preformed vitamin A can cause hepatitis or cirrhosis with doses of more than 100,000 IU per day. However, rare cases have occurred with dosages of 25,000 IU per day, and alcohol use increases the toxicity of vitamin A. Note that, although beta–carotene produces vitamin A in the body, it is not associated with this type of toxicity. Niacin also has hepatotoxic potential, although this may be limited to sustained–release formulas. - Several herbal supplements can be hepatotoxic. Kava, a botanical used for anxiety, was withdrawn from the market after suggestions of hepatotoxicity. Certain herbal products that are freely available to consumers (e.g., pennyroyal, skullcap, and chaparral) and Chinese herbal formulas that are not commercially distributed are associated with hepatotoxic effects.
The U.S. Food and Drug Administration has issued warnings regarding the hepatotoxicity of certain formulas touted for weight loss, such as LipoKinetix, although the active hepatotoxins in this product have not yet been identified. A surprising number of patients with acute hepatitis or acute liver failure have no identifiable cause of illness other than the use of herbal weight–loss products. Ephedra, which has been used for weight loss by millions of people, is associated with severe liver disease and has since been removed from the U.S. market. - A botanical extract, called milk thistle, has shown promise to protect the liver, but has yet to be proven effective in clinical trials. Silymarin, the active compound in milk thistle, has antioxidant, anti–inflammatory, and liver–regenerative effects. However, the scientific evidence is not yet clear on whether milk thistle should be used as a nutritional supplement.
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