Common Liver Toxins to Avoid: From Medications to Environmental Pollutants

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• Environmental Liver Toxins
• Aflatoxins and Liver Cancer Risk
• Acetaminophen Liver Toxicity
• Statin Medication Liver Damage
• Antibiotic-Induced Liver Injury
• Full Transcript

Environmental Liver Toxins

Common environmental liver toxins include petrochemicals, hydrocarbons, and air pollution from fuel exhaust. Dr. Simon Robson, MD, explains that the liver possesses a sophisticated detoxification system, primarily the cytochrome p450 enzymes. These enzymes evolved to process natural xenobiotics and poisons found in many plants and vegetables. While modern food processing has reduced these risks, exposure in certain workplaces or through pollution remains a potential source of liver injury.

Aflatoxins and Liver Cancer Risk

Aflatoxins are potent liver toxins produced by mold, commonly found on stored nuts and grains in subtropical climates. Dr. Simon Robson, MD, clarifies that while aflatoxins themselves may not cause significant direct liver damage, they dramatically promote liver cancer development in individuals with pre-existing liver injury, such as from hepatitis B. This is a significant concern in parts of the developing world, like Southern Africa, where aflatoxin exposure can lead to earlier-onset liver cancers, sometimes even without cirrhosis.

In the United States, aflatoxin levels are closely monitored. The highest levels are typically found in peanut butter, particularly homemade varieties. Dr. Robson assures that well-processed foods with expiration dates help limit exposure, making it a much smaller concern in the Western world compared to other liver toxins.

Acetaminophen Liver Toxicity

Acetaminophen, also known as paracetamol or Tylenol, is a leading cause of acute liver failure. Dr. Simon Robson, MD, emphasizes that the risk is not from standard doses in healthy individuals. The danger arises in patients with diminished liver functional reserves. Chronic alcoholics are exceptionally vulnerable because alcohol induces the liver enzymes that metabolize acetaminophen into toxic intermediates.

For a chronic alcoholic, especially one who is malnourished, there is no safe level of Tylenol exposure. Dr. Simon Robson, MD, states that this combination can lead to severe poisoning because the injured liver cannot adequately detoxify the medication. Ibuprofen and aspirin can also be toxic to the liver under certain conditions, making caution necessary with all over-the-counter pain relievers.

Statin Medication Liver Damage

Statins, widely prescribed to lower cholesterol, can cause liver toxicity marked by elevated liver enzymes. Dr. Simon Robson, MD, notes that while statin liver toxicity is a common reason for outpatient clinic visits, it rarely progresses to serious disease. The rate of liver transplantation due to statin toxicity is very low, estimated at only one or two patients per million per year.

This form of liver damage appears to be dose-dependent and is often seen after a massive increment in statin dosage, perhaps following a myocardial infarction. A key diagnostic challenge is differentiating statin-induced liver injury from underlying fatty liver disease, which often requires a liver biopsy. Fortunately, statin liver toxicity is usually reversible upon discontinuation of the drug or switching to a lower dose or alternative statin.

Antibiotic-Induced Liver Injury

Several commonly prescribed antibiotics are known to cause liver toxicity. Dr. Simon Robson, MD, identifies amoxicillin combined with clavulanic acid as one of the most common causes of antibiotic-induced liver injury. Other antibiotics with known hepatotoxic potential include erythromycin, isoniazid (used for tuberculosis exposure), and clarithromycin.

This type of liver injury is often idiosyncratic, meaning it is unpredictable and not directly dose-related. It may result from aberrant drug metabolism in a specific patient or an immunoallergic reaction to the medication. Dr. Anton Titov, MD, points out that regimens like clarithromycin and amoxicillin, used for H. pylori eradication, carry this risk alongside gastrointestinal side effects from accompanying proton pump inhibitors.

Full Transcript

Dr. Anton Titov, MD: Liver toxins to avoid are toxins coming from environmental pollution, petrochemicals, hydrocarbons, plant toxins, and medications. A leading expert in liver disease discusses how toxins affect liver metabolism. How does toxic insult to the liver lead to cancer in patients with diminished liver reserves? How to prevent liver toxicity from medications, especially acetaminophen/paracetamol (Tylenol), statins, and commonly used antibiotics? Liver toxins to avoid include air pollution, aflatoxins, and paracetamol (Tylenol).

Dr. Anton Titov, MD: What are common liver toxins to avoid?

Dr. Simon Robson, MD: Aflatoxins in peanut butter, especially homemade peanut butter. Fuel exhaust is very toxic to the liver. Monosodium glutamate (MSG) and artificial sweeteners (aspartame) are toxic to the liver.

There is no real liver detox regimen. There are many liver toxins to avoid. Pollution, aflatoxins, and paracetamol (Tylenol) are the most common ones. The key to a healthy liver is a moderate and healthy lifestyle and avoidance of toxins.

A medical second opinion helps to make sure a liver disease diagnosis is correct and complete. A medical second opinion also helps to choose the best treatment for liver failure caused by toxins in food and the environment.

Dr. Anton Titov, MD: Petrochemicals and hydrocarbons cause liver toxicity. Medications are a very important source of liver toxicity.

Dr. Simon Robson, MD: Acetaminophen, paracetamol, and Tylenol are toxic to the liver. Liver toxins to avoid also include acetaminophen and ibuprofen, especially if liver functional reserves are low due to alcoholism or fatty liver degeneration. Acetaminophen is a leading cause of acute liver failure. Ibuprofen and aspirin can also be toxic to the liver.

Dr. Simon Robson, MD: Statins can cause increased liver enzymes and acute liver toxicity. High doses of statins can lead to chronic liver toxicity. Amoxicillin with clavulanic acid can cause acute liver toxicity. Erythromycin liver toxicity also happens. Avoid liver toxins.

Dr. Anton Titov, MD: You mention the toxins that affect the liver—mushroom toxins, alcohol. What are some other common toxins that can damage the liver? There are also toxins called aflatoxins.

Dr. Simon Robson, MD: Aflatoxins tend not to be damaging to the liver, but in the setting of liver injury from other causes, they tend to promote the development of liver cancers. Aflatoxins are a problem in the developing world. Contamination of peanuts in peanut butter is probably the highest level of aflatoxins you will find in the United States, but obviously it is very closely monitored.

In parts of Southern Africa, like Mozambique, it is a subtropical climate. A lot of peanut meal and seeds and nuts are stored. They can get moldy. In those situations, aflatoxin exposure plus hepatitis B can lead to the onset of liver cancers at a much earlier age. Liver cancer starts earlier than one would completely anticipate.

Dr. Simon Robson, MD: Certainly, those liver cancers can develop in individuals who may not even have cirrhosis. They may not have much in the way of liver scarring. Aflatoxins are a problem, but most of the food that we eat is safe.

We mentioned the hygiene hypothesis; this plays a role in many autoimmune gastrointestinal diseases. One of the other benefits of having well-processed food, fresh foods with expiration limits and so forth, is that the levels of aflatoxins are somewhat limited. But clearly, it is a problem in parts of the developing world.

Dr. Anton Titov, MD: In the Western world, what are other common toxins that affect the liver?

Dr. Simon Robson, MD: Most of the time, the food that we select has been selected because it is not toxic to the liver, right? We have a whole series of enzymes in our liver called cytochrome P450. These liver enzymes are involved in drug metabolism.

These enzymes didn't arise for the purpose of detoxification of our pharmaceutical medications. Liver detoxification enzymes are there to remove potential xenobiotics, poisons that are present in cabbage, cauliflower, many root vegetables, and so forth. These are potential toxins.

Dr. Simon Robson, MD: But our liver takes them and inactivates them, then excretes them. As I said, the food has been selected over many years to have much lower levels of these toxins. But certainly, some agricultural products do have low levels of xenobiotics.

Pollution, petrochemicals, hydrocarbons—all these things can cause potential liver injury. Chemicals in workplaces, in patients working in chemical industries, also can damage the liver. But we don't see those toxins very often, I must say.

Dr. Anton Titov, MD: Most of the chemicals that we ingest are usually intentional. The most common toxins that affect the liver are pharmaceuticals. They can cause immediate toxicity.

Back with Tylenol: we take a certain dose of Tylenol, and it is going to be detoxified adequately. This adequate dose can't cause liver injury. But there are also subsets of patients, for example, with alcoholism. Alcoholics already have some degree of liver injury.

They could be totally hungover after binge drinking. They are very susceptible to acetaminophen, Tylenol, paracetamol poisoning because their liver has no resistance to paracetamol. The enzymes to metabolize the Tylenol are switched on dramatically. These hyperactive enzymes can generate toxic intermediates.

There is no safe level of Tylenol exposure for somebody who is a chronic alcoholic. It is particularly true if they are also chronically malnourished.

Other medications can cause idiosyncratic disease unpredictably. Statins that lower cholesterol can cause high levels of liver enzyme elevation. But typically, statins do not cause serious liver disease. The rates of liver transplantation after statin toxicity are very low.

Among patients who take statins, only one or two per million per year need liver transplantation because of statin liver toxicity. But lots of medications can potentially damage the liver, and we look out for those side effects.

Dr. Anton Titov, MD: Statins are very widely used medications, and they are being used more and more.

Dr. Simon Robson, MD: Yeah, so they not only damage muscles but can damage the liver. Among the drug toxicity cases that we see in an outpatient clinic, probably over half of liver toxicity (50%) are related to statin usage.

It is very difficult sometimes to work out whether liver toxicity is due to the statin or if liver toxicity happens because of the fatty liver disease that is associated with hyperlipidemia. In many instances, we may rely on a liver biopsy to actually determine if there is, in fact, drug toxicity or if it is just fatty liver disease.

Dr. Anton Titov, MD: Is there a way to predict statin toxicity on the liver? At least, is statin liver toxicity dose-dependent?

Dr. Simon Robson, MD: There is some evidence that statin liver toxicity is dose-dependent. We do not give statins to patients with more advanced liver disease, but patients with liver disease tolerate statins reasonably well.

Problems we see are in patients with massive increments in statin dosage. These statin liver toxicity cases happen maybe after the patient had a myocardial infarction. Because the effects of statins are not just in lowering lipids.

Dr. Anton Titov, MD: Statins also prevent inflammation and thrombosis at the actual vascular level. Statins have direct effects on the endothelium.

Dr. Simon Robson, MD: These are anti-inflammatory effects as well as lipid-lowering effects of statins. Some of our cardiology colleagues do increase the doses of statins quite high. Then we can see liver toxicity.

What we do know is that patients who have had liver toxicity with statins can be treated with statins again. We typically use a lower dose of statins or maybe an alternative form of statin. We then monitor those patients closely.

Dr. Anton Titov, MD: When the statin has been discontinued or the patient is switched to a different statin, is this toxicity not permanent? Does statin liver toxicity disappear?

Dr. Simon Robson, MD: Statin liver toxicity does seem to be reversed; it reverses. But the problem is that a patient may develop a very severe toxicity from statins. This can result in acute liver failure and require a transplant.

Most of the liver toxicity we see in North America is caused by acetaminophen (Tylenol). Antibiotics also cause liver toxicity typically. Sometimes INH [isoniazid], which is used here to treat patients who have been exposed to tuberculosis, can cause a lot of problems.

Dr. Anton Titov, MD: Isoniazid.

Dr. Simon Robson, MD: Yes, isoniazid. Then there are other antibiotics that can cause problems: ampicillin, clavulanic acid, its combinations.

Dr. Anton Titov, MD: Ampicillin with clavulanic acid is one of the most commonly prescribed antibiotics.

Dr. Simon Robson, MD: Yes, and one of the most common forms of liver injury from antibiotics. Curious, right? Erythromycin and many other medications can cause toxic liver injury.

Sometimes it is predictable; sometimes it is not predictable. It may be from aberrant metabolism. Maybe metabolism in that patient is different. Or maybe the immunology of a response to the altered drug is different. We call it "immunoallergic," so they have both immunological features as well as allergic features.

Dr. Anton Titov, MD: Clarithromycin and amoxicillin are one of the most commonly prescribed regimens against Helicobacter pylori.

Dr. Simon Robson, MD: Yeah, so there can be liver toxicity from that, as well as GI intolerance with the PPIs. PPIs are medications of the "proton pump inhibitors" class, such as Nexium and similar medications.

Liver toxins to avoid: air pollution, aflatoxins, and paracetamol (Tylenol).

Dr. Anton Titov, MD: Video interview with a leading liver disease expert. Mushrooms, amoxicillin, erythromycin, statins.