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Causes

By Mayo Clinic staff

Your liver performs hundreds of vital functions, including processing nutrients, regulating blood clotting and producing bile, a fluid that helps digest fats. It also removes most drugs and chemicals from your bloodstream, breaking them down so that they can be quickly eliminated from your body. But the conversion of these toxins creates byproducts that can be highly damaging to the liver. Although the liver has a great capacity for regeneration, constant exposure to toxic substances can cause serious — and sometimes irreversible — harm.

Toxins that damage the liver are divided into two broad groups:

  • Toxins that always cause liver damage (direct toxins). Some toxins always damage the liver. Dry cleaning solvents and the aptly named deathcap (amanita) mushroom belong in this group. They contain poisons that overwhelm the liver's ability to process them, and the resulting toxic byproducts destroy liver cells. If enough cells are destroyed, your liver can no longer function (liver failure).
  • Toxins that may cause liver damage (idiosyncratic toxins). Other toxins cause liver damage in only a small percentage of people who are exposed. Why certain substances lead to toxic hepatitis in some people but not in others isn't clear.

Nonprescription pain relievers
You don't have to look farther than your medicine cabinet to find the majority of liver toxins. Nonprescription pain relievers such as aspirin, ibuprofen (Advil, Motrin, others), naproxen (Aleve), and acetaminophen (Tylenol, others) can all damage your liver, especially if taken frequently or combined with alcohol.

Prescription drugs
In theory, all prescription drugs can injure the liver. Many don't cause serious harm, but hundreds may, including:

  • Halothane. Inhaled anesthetics such as halothane can cause severe liver damage, especially after repeated exposure. Women are twice as likely to experience halothane hepatoxicity as men are. People who are overweight also are at high risk.
  • Isoniazid. This common tuberculosis drug can cause hepatitis after only a month or two of treatment, especially in people age 50 and older.
  • Valproic acid and phenytoin. These anti-seizure medications have been known to cause toxic hepatitis and liver failure.
  • Methotrexate. This cancer drug, which is also used to treat psoriasis and rheumatoid arthritis, can damage the liver. Taking folic acid along with methotrexate may offset some of the drug's toxic effects.
  • Azathioprine (Imuran) and mercaptopurine. Azathiorpine is an anti-rejection drug used following kidney transplant and may also be used to treat rheumatoid arthritis. Mercaptopurine is used to treat certain types of cancer. Both can cause liver damage. This usually occurs soon after starting on the drugs, but the damage may be delayed.
  • Statins. The entire family of cholesterol-lowering drugs, which includes atorvastatin (Lipitor), lovastatin (Mevacor), pravastatin (Pravachol), simvastatin (Zocor), fluvastatin (Lescol) and rosuvastatin (Crestor), can damage your liver.
  • Some high blood pressure medications. High blood pressure medications that can damage the liver include calcium channel blockers and angiotensin-converting enzyme (ACE) inhibitors.
  • Ketoconazole. This common antifungal medication can cause toxic hepatitis and shouldn't be taken by anyone with liver problems.
  • Antibiotics. A wide range of antibiotics can injure the liver.
  • Anabolic steroids. These drugs cause liver inflammation by interfering with the flow of bile.

Herbs
Some herbs, such as milk thistle, may help heal the liver, but others can cause liver damage. Herbs can also interact with prescription drugs, leading to more serious side effects than either alone would cause.

Some of the herbs considered dangerous to the liver include:

  • Cascara
  • Chaparral
  • Comfrey
  • Kava
  • Ma-huang

Industrial chemicals
You usually must take herbs or medications for a period of time before liver damage occurs. But certain chemicals are different. Some are so toxic that a single unprotected exposure can cause liver failure. The United States government has identified 20 industrial chemicals that can cause acute liver injury or death, and more than 150 others that may lead to toxic hepatitis following longer exposure. Among the most common are the dry cleaning solvent carbon tetrachloride, the industrial chemical trichloroethylene and the herbicide paraquat.

Risk factors Symptoms
References
  1. Dienstag JL. Toxic and drug-induced hepatitis. In: Fauci AS, et al. Harrison's Principles of Internal Medicine. 17th ed. New York, N.Y.: McGraw-Hill; 2008. http://www.accessmedicine.com/resourceTOC.aspx?resourceID=4. Accessed Nov. 14, 2008.
  2. Lewis JH. Liver disease caused by anesthetics, toxins, and herbal preparations. In: Feldman M, et al. Sleisenger & Fordtran's Gastroinstestinal and Liver Disease: Pathophysiology, Diagnosis, Management. 8th ed. Philadelphia, Pa.: Saunders Elsevier; 2006. http://www.mdconsult.com/das/book/body/111481204-2/0/1389/0.html. Accessed Nov. 11, 2008.
  3. Friedman LS. Liver, biliary tract, & pancreas disorders. In: McPhee SJ, et al. Current Medical Diagnosis and Treatment 2009. 48th ed. New York, N.Y.: McGraw-Hill; 2009. http://www.accessmedicine.com/resourceTOC.aspx?resourceID=1. Accessed Nov. 11, 2008.
  4. Brown JA. Haz-Map: Information on hazardous chemicals and occupational disease. National Institutes of Health. http://hazmap.nlm.nih.gov. Accessed Nov. 12, 2008.
  5. Fountain FF. Isoniazid hepatotoxicity associated with treatment of latent tuberculosis infection: A 7-year evaluation from a public health tuberculosis clinic. Chest. 2005;128:116.
  6. Fontana RJ. Acute liver failure including acetaminophen overdose. Medical Clinics of North America. 2008;92:761.
  7. Fontana RJ. Acute liver failure due to drugs. Seminars in Liver Disease. 2008;28:175.
  8. Watkins PB. Aminotransferase elevations in healthy adults receiving 4 grams of acetaminophen daily. Journal of the American Medical Association. 2006;296:87.
  9. NCI drug dictionary. National Cancer Institute. http://www.cancer.gov/drugdictionary. Accessed Nov. 14, 2008.
  10. Picco MF (expert opinion). Mayo Clinic, Jacksonville, Fla. Oct. 28, 2008.

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Dec. 17, 2008

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