What is Hepatotoxicity?

Hepatotoxicity is a state of toxic damage to the liver. Drug-induced toxicity is the leading cause of acute liver failure in the United States. Antidotes are available for only a few hepatotoxins with one being N-acetylcysteine for acetaminophen overdose, which is a common drug most often associated with hepatotoxicity. Drug hepatotoxicity is rare and may not occur during clinical trials due to limited participants, compared to the number of consumers once the drug is on the market. Signs and symptoms can vary from fatigue, nausea, upper quadrant abdominal pain, loss of appetite, to jaundice. Adults are more susceptible to hepatotoxicity than children, and women are more susceptible than men. 


Some products can increase the risk for hepatotoxicity. For example, grapefruit juice induces hepatic enzymes and enzymes inducers enhance hepatotoxicity. Chronic alcohol abuse also increases risk because it lowers the level of liver proteins, which help metabolize drugs. Liver function tests provide more information for making a hepatotoxicity diagnosis. When evaluating test results or looking for signs and symptoms, any medications the patient is taking must be taken into account, including prescription drugs, over-the-counters, and herbals.

References

The New England Journal of Medicine, (February 1, 2006)
http://content.nejm.org/cgi/content/extract/354/7/731

Pubmed.gov
http://www.ncbi.nlm.nih.gov/pubmed/17451560?ordinalpos=2&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_DefaultReportPanel.Pubmed_RVDocSum

Risk Factors for Hepatotoxicity

Hepatotoxicity is a general term for liver damage. “Drug-induced liver injury is a potential complication of nearly every medication that is prescribed” (Meds and your Liver). When thinking of hepatotoxicity, Tylenol (acetaminophen) overdose usually comes to mind. Signs and symptoms of hepatotoxicity include nausea, vomiting, abdominal pain, loss of appetite, diarrhea, weakness, and jaundice.

It is not clear how hepatotoxicity can be prevented because it is poorly understood. One of the most important things you can do is to get checked for liver disease before starting any medications. Since most drugs are metabolized in the liver, proper function of the liver is essential. The first sign of damage to the liver is an increase in liver enzyme levels in the blood. When the liver is damaged, its enzymes are released into the bloodstream, where the levels can be measured by blood tests. This can be tested by liver function tests (FDA).

Common risk factors for hepatotoxicity include infection with hepatitis B, alcohol use, pregnancy, combination of drugs, and high levels of liver enzymes (Hepatotoxicity). These risk factors only correlate with hepatotoxicity and are not necessarily the cause of this disease. Taking Advil (ibuprofen) or any OTC medications should be taken within dosage and not mixed with other drugs or alcohol to avoid liver damage.



References

FDA www.fda.gov/ohrms/dockets/ac/02/slides

Hepatotoxicity http://aidsinfo.nih.gov/contentfiles/Hepatotoxicity_FS_en.pdf

Medications and your Liver http://www.beliefnet.com/healthandhealing/getcontent.aspx?cid=%0D%0A%09%09%09%09%09%0927863

Hepatotoxicity Hot Topic

Medications, whether prescription or over-the-counter, are used for just about everything in today’s society. People take medication for minor aches and pains, such as a headache or a stomach ache, and for more traumatic events where a prescription for a higher dose of pain relief is needed. What people often don’t know is that your liver is the organ responsible for processing these drugs. When you take more than the recommended dose, you can severely injure your liver. This is commonly referred to as drug-induced liver injury, or DILI.

Over-the-counter drugs can contain dangerous substances that, when abused, can lead to liver failure and even death. Prescription medications also may contain dangerous substances, and at a much higher dose, which is why a doctor’s order is required when receiving those drugs. If over-the-counter meds can cause this, why are some consumers not aware about the dangers of hepatotoxicity? 

A common pain reliever is acetaminophen, found in many over-the-counter medications as well as in a large handful of doctor-prescribed medications. Acetaminophen, although extremely helpful when used properly, can be toxic, and can even lead to an overdose, causing death. Too much of this drug and the liver can no longer process it, leaving free drugs in your body, which can cause devastating effects. Tylenol, one of the most common and widely used medication, contains acetaminophen.

Doctors often do not have the time to explain the consequences of over doses with Tylenol. Most people do not read labels when buying medications such as Tylenol and have no idea how much of the drug is actually present, which commonly leads to an overdose and acetaminophen toxicity. The Harris Interactive consumer poll from 2002 revealed statistics that prove this point: 

• 44% of consumers take more of a drug than the instructions state
• 63% took the next dose before they should have 
• 69% took a larger dose per day than instructed

These are the kind of decisions that lead to deaths cause by acetaminophen toxicity. Overdosing on acetaminophen, which is only eight tiny pills of extra strength Tylenol, is the leading cause of over-the-counter drug poisoning in the United States.

If acetaminophen is so dangerous, why have consumers not been properly warned until now? Medication is used for everything. The more medicine being consumed, the higher the risk for drug-induced toxicity. Acetaminophen is not by any means the only drug that can lead to liver damage, but it is one of the most widely used drugs that can do so. There is a broad category of drugs that can potentially cause liver problems, ranging from simple pain relievers to drugs used for high cholesterol. Certain risk factors believed to cause a higher risk of drug-induced liver disease in adults include obesity, pregnancy, chronic alcohol consumption, and many more.

References:

http://www.lef.org/protocols/appendix/otc_toxicity_01.htm  

http://www.liverdisease.com/medications_hepatitis.html  

http://www.merck.com/mmpe/sec03/ch024/ch024c.html

Hepatotoxicity in the News

FDA Warns of Hepatotoxicity Risk with Xenical and Alli (orlistat)

The FDA has warned healthcare professionals and consumers about reports regarding reports of liver-related events in patients who take orlistat. Orlistat is sold in the United States under the trade names of Xenical and Alli. So far there has been 32 reports of serious liver injuries which consist of liver failure. The FDA has advised healthcare professionals to be cautious when writing prescriptions for orlistat. Xenical is only given as prescribed medication to treat obesity and to assist in diets involving weight loss.

For further information refer to: http://www.empr.com/FDA-warns-of-hepatotoxicity-risk-with-Xenical-and-Alli-orlistat/article/147229/

FDA Warns Consumers to Stop Using Hydroxycut Products
Dietary Supplements Linked to One Death; Pose Risk of Liver Injury

In May 2009 the FDA warned consumers to stop consuming Hydroxycut products, which are developed by Iovate Health Sciences Inc. The FDA has discovered that Hydroxycut has a negative effect on the liver and may cause serious health problems. These problems range from jaundice to elevated liver enzymes. Some other symptoms include nausea, fatigue, weakness, and abdominal pain. Iovate has agreed to recall Hydroxycut products from the market. Hydroxycut is used as a dietary supplement used for quickly burning fat and losing weight.

For further information refer to: http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm149575.htm

Tylenol (Acetaminophen) May Cause Liver Damage

Tylenol is one of the most popular over-the-counter pain killers in the United States. However, the FDA has discovered some cases where the intake of Tylenol may cause liver damage. Even though the occurrence is rare, the FDA advises consumers to be cautious when using this medication. Taking the recommended dosages will not necessarily cause severe liver damage, but there is a chance of increasing liver enzymes in the blood which may cause injury to the liver.

For further information refer to: http://www.medicinenet.com/tylenol_liver_damage/article.htm

Dangerous Drugs

The risk of hepatotoxicity is serious, but are the drugs to blame? It's easy to find opinions on the internet that cover the range of extremes. One website that sells herbal vitamins also urges customers to refrain from buying Tylenol or Nyquil because "THEY KILL!" (Broer, 2009). While it's true that these drugs can kill under certain circumstances, they are not dangerous if taken as recommended. Even herbal vitamins can be deadly if taken in excess.

Even if a drug itself is not dangerous, the packaging or directions may lead consumers to take more than the recommended dose. In July, the FDA announced a voluntary recall of concentrated acetaminophen drops because the packaging was similar to less-concentrated drops of the same brand, leading to "inadvertent overdosing" (FDA, 2009). In addition to recalling unsafe products, the FDA also takes a proactive approach to preventing hepatotoxicity. Earlier this year, the organization issued a rule that packaging for OTC pain relievers must conspicuously display warnings and active ingredients such as acetaminophen (FDA, 2009).

Although there are organizations in place to regulate drug safety, consumers should still be responsible when taking any medication. On the other side of the spectrum, there are those with an extremely lax attitude toward OTC drugs, which is an equally dangerous view. In a New York Times article from July, the author down-played the risk of acetaminophen hepatotoxicity by citing "only about 2,000 deaths" compared to the higher number of deaths linked to other pain relievers like aspirin, and a quote from a toxicologist implied that people should worry about ibuprofen, not acetaminophen (Parker-Pope, 2009).

It's best if consumers take a moderate approach to any medication, whether it be prescription, OTC, or herbal. They shouldn't avoid all drugs, but they also shouldn't be too careless.

References

Broer, T, (7-9-2009), http://www.healthmasters.com/blog/do-not-use-tylenol-or-nyquil-they-kill

Parker-Pope, T, (7-6-2009), http://www.nytimes.com/2009/07/07/health/ 07well.html

FDA, (7-13-2009), http://www.fda.gov/Safety/Recalls/ucm171780.htm

FDA, (4-28-2009), http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm149573.htm

Nursing Implications

Although we've focused on acetaminophen because of its popularity, many drugs can lead to hepatotoxicity. Nurses should be knowledgeable about potential interactions and always be aware that the more drugs a patient takes, especially those that act in the liver, the greater the risk for hepatotoxicity. One of the best ways, and sometimes only way, to prevent hepatotoxicity is patient teaching.

• Parents should consider over-the-counters to be just as dangerous as prescription drugs, and all medicine should be kept out of children's reach. Parents may also want to be careful if they have depressed older children, as sometimes teenagers will take too many Tylenols without knowing this can actually hurt them (Lilley, 2007).

• Nurses should also teach their patients to be aware of what medications they're taking, including active ingredients and dosages. The maximum daily dose of acetaminophen is 4000 mg (for adults with healthy livers), and it could be present in several different medications the patient takes. If patients complain that the recommended dose doesn't work, then they should talk to their nurse practitioner or doctor about the problem.

• Although nurses should encourage patients to drink moderately, chronic drinkers should receive non-judgmental information about alcohol use and medication. Nurses may need to recommend a different medication that would be safer for them to take. Many serious cases of acetaminophen overdose have occurred in alcoholics (Lilley, 2007).

• When assessing patients, ask patients about:

-their alcohol use

-all medications they take, including prescriptions, OTCs, and

herbals

-any history of liver problems

Reference

Lilley, Harrington, & Snyder, 2007, Pharmacology and the Nursing Process