Steroids and liver damage

A number of unhealthy and damaging effects may result from the use of anabolic steroids that can lead to both emotional and physical problems. Studies have shown that abuse of steroids can increase aggressive behavior, cause mood swings, and impair judgment. Other reported effects include male-pattern baldness, acne, and liver damage. Using steroids can increase the risk of heart disease, stimulate the growth of certain cancers, and worsen other medical problems.

Steroids taken orally (by mouth) have been linked to liver disease. Steroids taken by injection (by needle) can increase the risk of infectious diseases such as hepatitis or AIDS. In one study, 25% of steroid users shared needles.

Equally troubling, anabolic steroids can prevent a person from reaching their natural height. Young, developing bodies are particularly sensitive to anabolic steroids, and some of the side effects may be permanent. In addition to stunting height among growing adolescents, these steroids can trigger the growth of breasts in males. This can happen because the chemical structure of certain anabolic steroids is converted to the female hormone estrogen by a chemical reaction in the body.

On the other hand, females may develop a deeper voice, an enlarged clitoris, and facial hair growth caused by the masculinizing effect of testosterone-like hormones. Women and girls also may experience the loss of scalp hair as well. These are potentially permanent side effects. Although long-term studies are scarce, experts believe that some harmful effects may not appear until many years after the abuse of these drugs.

Possible Health Effects of Steroid Use:

  • Increased risk of liver, kidney, and prostate cancer
  • High blood pressure, which increases the chance of heart attack and stroke
  • Abnormal cholesterol levels, which increase the chance of heart attack and blood vessel disease
  • Premature stopping of bone development and linear growth (height)
  • Damage to the liver, including the formation of blood filled liver cysts that can rupture, causing death
  • Acne
  • Increased risk of HIV and hepatitis because of risks from sharing needles
  • In males: Baldness, breast formation, shrunken testicles, and the temporary inability to father a child
  • In females: Decreased breast size, irregular menstrual cycles, and masculine appearance, particularly an enlarged clitoris, facial and body hair, and a deep voice

Psychological Symptoms:

  • Mood swings
  • Sleep disruption
  • Aggressive behavior
  • Extreme irritability
  • Delusions
  • Impaired judgment because of feelings that nothing can hurt you
  • Paranoid jealousy
  • Euphoria or an exaggerated feeling of well-being
  • Depression after stopping steroids
  • Lack of sexual drive after stopping steroid use

Steroid Use and Liver Cancer

Although well-documented reports linking steroids to liver cancer are rare, as more athletes use drugs to improve their performance or build their bodies, many types of dangerous side effects from the abuse of anabolic steroids are becoming known — and events are becoming more frequent.

Recently, there have been many instances in the news about famous athletes and performance-enhancing drugs, sometimes referred to as “doping.” In most cases, the drugs that are being used are anabolic steroids. These drugs are manufactured steroids that behave like the male hormone testosterone. In the United States, it is illegal to use anabolic steroids without a prescription.

“Anabolic steroids are male-related hormones that can be used to increase muscle mass. When these drugs are abused they can have many side effects, including liver damage,” notes George Y. Wu, MD, PhD, a professor of medicine, chief of the hepatology section, and Herman Lopata chair in hepatitis research at the University of Connecticut Medical Center in Farmington.

Liver Cancer: What Anabolic Steroids Can Treat

Anabolic steroids, under a doctor’s prescription, will treat certain conditions in which increasing bone strength and muscle mass are required for health reasons. These medications can be helpful in the following types of cases:

  • Delayed puberty
  • Testosterone deficiency
  • AIDS-related weakness

Liver Cancer: Anabolic Steroid-Related Liver Damage

Liver damage from anabolic steroids can cause a condition called cholestasis. With this condition, bile, a digestive fluid made in your liver, cannot get to where it needs to go and leaks out into your blood. Symptoms include:

  • Itching
  • Nausea
  • Loss of appetite
  • Dark urine
  • Jaundice — the yellow discoloration of your eyes and skin

Damage to the liver is evident when enzymes called aminotransferases leak out of damaged liver cells into your bloodstream.

Another important point about anabolic steroids: They can be addictive. These steroids can cause steroid craving that leads to the need for more frequent and higher drug doses. Liver damage has been shown to be related to the cumulative effects of higher and more frequent use.

Liver Cancer: Can Anabolic Steroids Cause It?

Dr. Wu says that reports exist showing a slightly increased risk of developing liver cancer with long-term use of high-dose anabolic steroids. However, he says, “the scientific evidence supporting a cause-and-effect relationship is weak.”

But these steroids are known to cause tumors that form in your liver. Called hepatic adenomas, these tumors are not cancerous. However, they are dangerous because they can rupture and cause serious bleeding in the liver. There have been several reported deaths caused by bleeding from ruptured hepatic adenomas. The link between hepatic adenomas and anabolic steroid use in athletes is increasing. Recently, a case of a hepatic adenoma turning into liver cancer was reported.

Liver Cancer: Anabolic Side Effects

While there is not a strong link between liver cancer and anabolic steroids, there is strong evidence for serious liver damage. Other side effects of anabolic steroids include:

  • High blood pressure
  • Increased levels of bad cholesterol
  • Mood swings
  • Aggressive behavior
  • Infertility in men
  • Menstrual abnormalities in women

If you are an athlete or a body-builder and you are tempted to use anabolic steroids, consider that besides the legal and social risks involved, these drugs can and do cause life-theatening medical complications.

7 ways anabolic steroids affect your health

Androgenic-anabolic steroids (AAS) have been used to enhance athletic performance since the 1940s, but some of the health risks of steroid abuse have only recently come to light. Anabolic steroids have widespread effects on the body and its internal systems, so it’s not surprising that aside from their potential effect on muscle growth, they can harm other cells and organs. That’s why regular health screening and blood testing is so important. Find out more with our Sports Hormone Check.

How do anabolic steroids work?

Anabolic steroids are synthetic derivatives of the hormone testosterone which amongst other things is responsible for muscle development – “the anabolic effect”, and the development of male sexual characteristics – “the androgenic effect”.

Anabolic steroids work in several different ways in the body:

  1. When we lift heavy weights we create tiny micro-tears in muscle fibres. Testosterone stimulates the creation of new and bigger muscle fibres in reaction to this. Anabolic steroids tend to cause an exaggerated version of this reaction due to the high doses people use.
  2. Anabolic steroids stimulate production of growth hormone (GH) which in turn stimulates the production of IGF-1. IGF-1 has growth-promoting effects on almost every cell in the body especially skeletal muscle, cartilage and bone.
  3. Intense exercise releases cortisol known as the stress hormone, which breaks down muscle tissue. Anabolic steroids inhibit this breakdown resulting in an overall anabolic effect.
  4. There is evidence that anabolic steroids may increase oxygen uptake and increase cardiac output.
  5. Anabolic steroids may also improve athletic performance by increasing aggressive behaviour.

Unintended physical consequences

A common misconception is that because anabolic steroids are a man-made derivative of a hormone occurring naturally in the body they should be safe to supplement with. The human body controls the blood and tissue levels of testosterone within a small range as too high or low a concentration can be harmful. However the typical doses taken as supplements by athletes are significantly higher than the amount that naturally circulates in our system. Use of anabolic steroids can therefore lead to multiple harmful physical side effects with shrunken testicles and male breast growth probably the most well known. An excess of androgens resulting from steroid use can also lead to male-pattern baldness, severe treatment resistant acne as well as altered libido.

Chronic steroid use causes the body to stop its own internal production of testosterone in an effort to maintain a constant level. This can lead to shrunken testicles that can no longer produce testosterone themselves. In addition, testosterone is converted to oestrogens which are important for modulating libido, erectile function and sperm generation. However an excess of testosterone can raise oestrogen to abnormal levels resulting in gynecomastia or the enlargement of male breasts. These effects can be permanent.

What lies beneath

In addition to the more noticeable effects associated with steroid use, there are other potential consequences that may not be so obvious but can pose a serious health risk. While blood testing can help pick up some of the abnormalities associated with excessive anabolic steroid use it is important to be aware that many of the harmful effects may not cause abnormalities in the blood until it is too late. It is also important to be aware that many of the treatments for the conditions described below are less likely to work with continued steroid use.

Here we describe 7 ways that anabolic steroids can damage your health without you even realising it:

1. Cardiovascular disease

There have been many studies on the impacts of anabolic steroids on the cardiovascular system in athletes and bodybuilders. Steroids have been shown to increase levels of LDL (bad cholesterol) and decrease levels of HDL (good cholesterol) – this increases the risk of atherosclerosis (hardening of the arteries) and heart disease such as angina, heart attacks and sudden cardiac death. Similarly steroid use is also associated with elevated C-reactive protein (CRP) levels – CRP is an marker of inflammation within the body and there is evidence that constant high levels may predispose people to cardiovascular disease. Find out more with our Sports Hormone Check.

Chronic steroid use can affect heart muscle causing a condition known as left ventricular hypertrophy which is an enlargement and thickening of the walls of the heart’s main pumping chamber. The enlarged heart muscle loses elasticity and eventually may fail to pump with as much force as needed. This is known as heart failure and is a common cause of disability and death in the elderly.

High blood pressure has been reported in some cases of anabolic steroid use which further increases the risk of cardiovascular disease.

2. Liver toxicity

Most metabolism of anabolic steroids occurs in the liver which is therefore prone to damage. Whilst athletes with pre-existing liver conditions are most at risk the damage can occur in anyone. The two markers of liver stress most commonly elevated in users of anabolic steroids are the enzymes ALT and AST. These enzymes are necessary for amino acid metabolism in the liver and will leak into the bloodstream as the liver becomes inflamed or damaged. ALP and GGT are also important markers of liver health during steroid use, and elevated levels can indicate liver toxicity. It is important to be aware that significant liver damage can be occurring even with normal liver function tests and that often the blood levels of these liver markers only start rising when the damage is severe enough. Find out more with our Sports Hormone Check.

3. Kidney injury

One of the kidneys many crucial functions is acting as a filter for the blood, removing excess waste products in the body. Bodybuilders frequently use dietary supplements including protein, creatine and vitamins to build strength and muscle bulk. High-protein intake is a concern as it increases the demand on the kidneys to filter off the excess products of protein metabolism. Often this is not a huge problem on its own, but when high-protein intake is combined with anabolic steroid use, this compounds the load on the kidneys and can lead to scarring and possibly kidney failure. Find out more with our Sports Hormone Check.

4. Infertility

Chronic anabolic steroid use causes a decrease in luteinising hormone (LH), and follicle-stimulating hormone (FSH) which are needed for sperm generation. This can cause a decrease in sperm count and mobility. Decreases in LH and FSH can be seen within 24 hours of beginning anabolic steroid use, and infertility may result within months. Usually infertility is reversible typically within 1 year of stopping steroid use, but it can take longer particularly in long-term users.

Men may also experience priapism, impotence, difficulty or pain with urination, and a possible increased risk for prostate cancer, which is why a regular prostate check is important. Find out more with our Sports Hormone Check.

5. Impaired glucose tolerance

Studies have shown that anabolic steroid use affects the body’s ability to handle sugar and can lead to type 2 diabetes. This can have a devastating health impact and further increase the risk of kidney damage, heart disease, strokes and blindness amongst other things. Testing of fasting blood sugar can help pick this up early before these complications start to arise. Find out more with our Sports Hormone Check.

6. Blood disorders

Anabolic steroid use increases stimulates the production of red blood cells and also increases the levels of haemoglobin (the protein in red blood cells that carries oxygen) and haematocrit (the percentage of red blood cells in the blood). This can result in a condition known as testosterone–induced polycythaemia or “sludging”. This causes the blood to become thicker which can in some people trigger life threatening blood clots to form in the bloodstream. Find out more with our Sports Hormone Check.

7. Thyroid dysfunction

Studies have shown negative effects of anabolic steroids on thyroid function. The thyroid is responsible for a huge number of important metabolic processes, and a thyroid hormone imbalance can cause a wide range of health issues (refer to our blog on thyroid function for more information). An annual thyroid check is important to keep track of thyroid function. Find out more with our Thyroid Check.

The importance of blood work

The use of anabolic steroids can lead to a number of negative health consequences most notably with cardiovascular and liver health. By the time physical symptoms of these develop, permanent harm may already have been done. The safest medical advice that any health professional would give you is to stop using these due to their risks. However, if you chose to continue taking these supplements it is important to be vigilant for any signs you may be harming your health. As discussed in this blog some of these effects can be identified in blood work before physical symptoms become apparent. These are the blood tests we recommend which are included in our Sports Hormone Check:

  • Cholesterol status – there are many factors which contribute to your cardiovascular health. Your cholesterol (both high density and low density lipoproteins) and triglyceride levels are one risk factor we can assess by blood testing.
  • Inflammation – the biomarkers c-reactive protein and creatine kinase provide insight into cardiovascular disease and muscle damage.
  • Liver function test – your liver processes drugs and filters toxic chemicals. Liver damage is often evident from the assessment of liver enzymes and other key markers of liver function.
  • Kidney function test – your kidneys filter waste from your body. Extreme athletes are more at risk of kidney failure due to high protein intake, excessive muscle breakdown from intense exercise as well as anabolic steroid use. Measuring key waste products as well as electrolytes, minerals and glucose provides good insight into kidney function.
  • Full blood count – measuring steroid-induced increases in red blood cell count, haematocrit, and haemoglobin concentrations are important in determining the risk of heart attack or stroke.
  • Hormone profile – supplementing with anabolic steroids can cause changes in hormone profile over time. Key hormones to measure include the androgens testosterone and free testosterone, as well as FSH, LH and oestradiol.

It is important to understand what your own ‘normal’ levels are for your blood biomarkers, and to track changes to these over time. Monitoring changes in your health data typically provides greater insight than a single isolated result, and will allow you to track any improvements or declines in performance.

If you want to reduce your health risks, then don’t take anabolic steroids. But if you are supplementing then visit our Sports Hormone Check to understand more about how blood testing and health screening can help manage your risk.

What are some important examples of drug-induced liver disease?

Acetaminophen (Tylenol)

An overdose of acetaminophen can damage the liver. The probability of damage as well as the severity of the damage depends on the dose of acetaminophen ingested; the higher the dose, the more likely it is that there will be damage and the more likely it is that the damage will be severe. (The reaction to acetaminophen is dose-dependent and predictable; it is not idiosyncratic – peculiar to the individual.) The liver injury from an overdose of acetaminophen is a serious matter since the damage can be severe and result in liver failure and death. In fact, acetaminophen overdose is the leading cause of acute (rapid onset) liver failure in the U.S. and the United Kingdom.

For the average healthy adult, the recommended maximum dose of acetaminophen during a 24-hour period is 4 grams (4000 mg) or eight extra-strength tablets. (Each extra-strength tablet contains 500 mg, while each regular strength tablet contains 325 mg.) Among children, the dose of acetaminophen is determined on the basis of each child’s weight and age, explicitly stated in the package insert. If these guidelines for adults and children are followed, acetaminophen is safe and carries essentially no risk of liver injury. A person who drinks more than two alcoholic beverages per day, however, should not take more than 2 grams (2000 mg) of acetaminophen over 24 hours, as discussed below, since alcohol makes the liver susceptible to damage from lower doses of acetaminophen.

A single dose of 7 to 10 grams (7000 – 10,000 mg) of acetaminophen (14 to 20 extra-strength tablets), twice the recommended dose, can cause liver injury in the average healthy adult. Among children, a single dose of 140 mg/kg (body weight) of acetaminophen can result in liver injury. Nevertheless, 3 to 4 grams ((3000 to 4000 mg) taken in a single dose or 4 to 6 grams (4000 to 6000 mg) over 24 hours have been reported to cause severe liver injury in some people, sometimes even resulting in death. It seems that certain individuals, for example, those who regularly drink alcohol, are more prone than others to developing acetaminophen-induced liver damage. Other factors that increase a person’s risk for damage from acetaminophen include the fasting state, malnutrition, and concomitant administration of some other drugs such as phenytoin (Dilantin), phenobarbital, carbamazepine or isoniazid .

Please read the Tylenol Liver Damage article for a detailed discussion of the symptoms, mechanisms of acetaminophen toxicity, treatment (early use of N-acetylcysteine), and prevention.

Statins

Statins are the most widely used medications to lower “bad” (LDL) cholesterol in order to prevent heart attacks and strokes. Most doctors believe that statins are safe for long-term use, and important liver injury is rare. Nevertheless, statins can injure the liver. The most common liver-related problem caused by statins is mild elevations in blood levels of liver enzymes (ALT and AST) without symptoms. These abnormalities usually improve or completely resolve upon stopping the statin or reducing the dose. There is no permanent liver damage.

Patients with obesity have an increased chance of developing diabetes, non-alcoholic fatty liver disease (NFALD), and elevated blood cholesterol levels. Patients with fatty liver often have no symptoms, and the abnormal tests are discovered when routine blood testing is done. Recent studies have found that statins can be used safely to treat high blood cholesterol in patients who already have fatty liver and mildly abnormal liver blood tests when the statin is started. In these patients, doctors may choose to use statins at lower doses and monitor liver enzyme levels regularly during treatment.

Nevertheless, idiosyncratic liver toxicity capable of causing severe liver damage (including liver failure leading to liver transplantation) has been reported with statins. The frequency of severe liver disease caused by satins is likely in the range of 1-2 per million users. As a precaution, the FDA labeling information advises that liver enzyme blood tests should be performed before and 12 weeks following the initiation of statin treatment or increase in dose, and periodically thereafter (for example, every six months).

Nicotinic acid (Niacin)

Niacin, like the statins, has been used to treat elevated blood cholesterol levels as well as elevated triglyceride levels. Also like the statins, niacin can damage the liver. It can cause mild transient elevations in blood levels of AST and ALT, jaundice, and, in rare instances, liver failure. Liver toxicity with niacin is dose-dependent; toxic doses usually exceed 2 grams per day. Patients with pre-existing liver diseases and those who drink alcohol regularly are at higher risk for developing niacin toxicity. The sustained-release preparations of niacin also are more likely to cause liver toxicity than the immediate-release preparations.

Amiodarone (Cordarone)

Amiodarone (Cordarone) is an important medication that is used to treat irregular heart rhythms such as atrial fibrillation and ventricular tachycardia. Amiodarone can cause liver damage ranging from mild and reversible liver blood enzyme abnormalities, to acute liver failure and irreversible cirrhosis. Mild liver blood test abnormalities are common and typically resolve weeks to months after stopping the drug. Serious liver damage occurs in less than 1% of patients.

Amiodarone differs from most other drugs because a substantial amount of amiodarone is stored in the liver. The stored drug is capable of causing fatty liver, hepatitis, and, more importantly, it can continue to damage the liver long after the drug is stopped. Serious liver damage can lead to acute liver failure, cirrhosis, and the need for liver transplantation.

Methotrexate (Rheumatrex, Trexall)

Methotrexate (Rheumatrex, Trexall) has been used for the long-term treatment of patients with severe psoriasis, rheumatoid arthritis, psoriatic arthritis, and some patients with Crohn’s disease. Methotrexate has been found to be a cause of liver cirrhosis in a dose-dependent fashion. Patients with pre-existing liver diseases, obese patients, and those who drink alcohol regularly are particularly at risk of developing methotrexate-induced cirrhosis. In recent years, doctors have substantially decreased methotrexate liver damage by using low doses of methotrexate (5-15 mg) given once a week and by carefully monitoring liver blood tests during therapy. Some doctors also perform liver biopsies on patients without liver symptoms after two years (or after a cumulative dose of 4 grams of methotrexate) to look for early liver cirrhosis.

Antibiotics

Isoniazid (Nydrazid, Laniazid). Isoniazid has been used for decades to treat latent tuberculosis (patients with positive skin tests for tuberculosis, without signs or symptoms of active tuberculosis). Most patients with isoniazid-induced liver disease only develop mild and reversible elevations in blood levels of AST and ALT without symptoms, but approximately 0.5% to 1% of the patients develop isoniazid-induced hepatitis. The risk of developing isoniazid hepatitis occurs more commonly in older patients than younger patients. The risk of serious liver disease is 0.5% in healthy young adults, and rises to more than 3% in patients older than 50. At least 10% of the patients who develop hepatitis go on to develop liver failure and require liver transplantation. The risk of isoniazid liver toxicity is increased with chronic regular alcohol intake, and with concomitant use of other medications such as Tylenol and rifampin (Rifadin, Rimactane).

Early symptoms of isoniazid hepatitis are fatigue, poor appetite, nausea, and vomiting. Jaundice may then follow. Most patients with isoniazid hepatitis recover fully and promptly after stopping the drug. Severe liver disease and liver failure mostly occur in patients who continue to take isoniazid after the onset of hepatitis. Therefore, the most important treatment for isoniazid liver toxicity is early recognition of hepatitis and discontinuation of the isoniazid before serious liver injury has occurred.

Nitrofurantoin. Nitrofurantoin is an anti-bacterial drug that is used to treat urinary tract infections caused by many gram-negative and some gram-positive bacteria. (Nitrofurantoin was approved by the FDA in 1953.) There are three forms of nitrofurantoin available: a microcrystalline form (Furadantin), a macrocrystalline form (Macrodantin), and a sustained release, macrocrystalline form used twice daily (Macrobid).

Nitrofurantoin can cause acute and chronic liver disease. Most commonly, nitrofurantoin causes mild and reversible elevations in blood levels of liver enzymes without symptoms. In rare instances, nitrofurantoin can cause hepatitis.

Symptoms of nitrofurantoin hepatitis include:

  • fatigue,
  • fever,
  • muscle and joint aches,
  • poor appetite,
  • nausea,
  • weight loss,
  • vomiting,
  • jaundice, and
  • sometimes itching.

Some patients with hepatitis also have a rash, enlarged lymph glands, and nitrofurantoin-induced pneumonia (with symptoms of cough and shortness of breath). Blood tests usually show elevated liver enzymes and bilirubin. Recovery from hepatitis and other skin, joint, and lung symptoms is usually rapid once the drug is stopped. Serious liver disease such as acute liver failure and chronic hepatitis with cirrhosis mostly occur in patients who continue the drug despite developing hepatitis.

Augmentin. Augmentin is a combination of amoxicillin and clavulanic acid. Amoxicillin is an antibiotic that is related to penicillin and ampicillin. It is effective against many bacteria such as H. influenzae, N. gonorrhea, E. coli, Pneumococci, Streptococci, and certain strains of Staphylococci, Addition of clavulanic acid to amoxicillin in Augmentin enhances the effectiveness of amoxicillin against many other bacteria that are ordinarily resistant to amoxicillin.

Augmentin has been reported to cause cholestasis with or without hepatitis. Augmentin-induced cholestasis is uncommon, but has been implicated in hundreds of cases of clinically apparent acute liver injury. Symptoms of cholestasis (jaundice, nausea, itching) usually occur 1-6 weeks after starting Augmentin, but the onset of liver disease can occur weeks after stopping the Augmentin. Most patients recover fully in weeks to months after stopping the medication, but rare cases of liver failure, cirrhosis, and liver transplantation have been reported.

Other antibiotics have been reported to cause liver disease. Some examples include minocycline (an antibiotic related to tetracycline), and Cotrimoxazole (a combination of sulfamethoxazole and trimethoprim).

Nonsteroidal antiinflammatory drugs (NSAIDs)

Nonsteroidal antiinflammatory drugs (NSAIDs) are commonly prescribed for the bone and joint-related inflammation such as arthritis, tendinitis and bursitis. Examples of NSAIDs include aspirin, indomethacin (Indocin), ibuprofen (Motrin), naproxen (Naprosyn), piroxicam (Feldene), and nabumetone (Relafen). Approximately 30 million Americans take NSAIDs regularly!

NSAIDs are safe when used properly and as prescribed by doctors; however, patients with cirrhosis and advanced liver disease should avoid NSAIDs since they can worsen liver function (and cause kidney failure as well).

Serious liver disease (such as hepatitis) from NSAIDs, occur rarely (in approximately 1-10 patients per 100,000 who use prescriptions). Diclofenac (Voltaren) is an example of an NSAID that has been reported to cause hepatitis slightly more frequently, in approximately 1-5 per 100,000 users of the drug. Hepatitis usually resolves completely after stopping the drug. Acute liver failure and chronic liver disease, such as cirrhosis, have been reported rarely.

Tacrine (Cognex)

Tacrine (Cognex) is an oral medication used for treating Alzheimer’s disease. (The FDA approved tacrine in 1993.) Tacrine has been reported to cause abnormal elevations in blood liver enzymes commonly. Patients may report nausea, but hepatitis and serious liver disease are rare. Abnormal tests usually become normal after tacrine is stopped.

Disulfiram (Antabuse)

Disulfiram (Antabuse) is a medication occasionally prescribed to treat alcoholism. It discourages drinking by causing nausea, vomiting, and other unpleasant physical reactions when alcohol is ingested. Disulfiram has been reported to cause acute hepatitis. In rare cases, disulfiram-induced hepatitis can lead to acute liver failure and liver transplantation.

Vitamins and Herbs

Excess intake of vitamin A, taken for years, can damage the liver. It is estimated that more than 30% of the U. S. population takes supplements of vitamin A, and some individuals are taking vitamin A at high doses that may be toxic to the liver (greater than 40,000 units/ day). Vitamin A-induced liver disease includes mild and reversible elevation in blood liver enzymes, hepatitis, chronic hepatitis with cirrhosis, and liver failure.

The symptoms of vitamin A toxicity may include bone and muscle aches, orange discoloration of skin, fatigue, and headache. In advanced cases, patients will develop enlarged livers and spleens, jaundice, and ascites (abnormal buildup of fluid in the abdomen). Patients who drink alcohol heavily and have other preexisting liver disease are at increased risk of liver damage from vitamin A. Gradual improvement in the liver disease usually occurs after stopping vitamin A, but progressive liver damage and failure may occur in severe vitamin A toxicity with cirrhosis.

Liver toxicity also has been reported with herbal teas. Examples include Ma Huang, Kava Kava , pyrrolizidine alkaloids in Comfrey, germander, and chaparral leaf. Amanita phylloides is a liver-toxic chemical found in poisonous mushrooms. Consumption of a single poisonous mushroom can lead to acute liver failure and death.

Drugs and Liver Disease

Table of Contents Authored By Marisa Crane, BS Reviewed By Lauren Brande, MA

The Function of the Liver

The liver plays an extremely important role in the body. It ensures the removal of toxins and has numerous other functions, including:

  • Fat metabolism: The liver cells — or hepatocytes — are able to process dietary and stored fats into energy. In addition, the liver acts as a key player in our exocrine systems by producing bile acids, which are secreted into our digestive tracts. There, they function to break down and facilitate the intestinal absorption of fats that we consume in our diet. Supplementing this activity, the liver also synthesizes cholesterol to aid in fat transport.
  • Carbohydrate metabolism: The liver helps to regulate blood sugar by utilizing stored glycogen when glucose levels are low and removing it from the blood when levels are high.
  • Protein metabolism: The liver breaks down proteins and converts amino acids into useable energy, or further processes them into needed macronutrients. Ammonia is a toxic byproduct of this process. As ammonia builds, the liver further modifies it into a chemical known as urea, which travels through the circulation to the kidneys, where it is safely released in urine.

Further functions of the liver include 1,2:

  • Producing circulating proteins that help blood clot normally.
  • Breaking down old blood cells.
  • Processing the hemoglobin protein found in red blood cells in order to salvage/recycle the iron that it contains.
  • Storing minerals (such as iron) and vitamins to release when necessary.
  • Removing bacteria and other foreign bodies from the bloodstream.
  • Eliminating excess bilirubin, a component released from red blood cells that are damaged or otherwise at the end of their lifecycle which can be harmful to the body and brain.

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How the Liver Metabolizes Drugs

When blood enters the liver via the portal vein, it carries nutrients as well as drugs and other toxic substances the individual may have consumed 1. The liver’s job is to detoxify these drugs and remove the byproducts resulting from the process of metabolism 1.

The majority of drugs are fat-soluble, meaning that they are difficult to pass in urine. The enzymes in the liver work to break down these substances and convert them into water-soluble forms, which can then pass in bile and/or urine.

A hepatocyte, or liver cell, contains several sub-cellular organelles that serve as the primary sites of drug metabolism. Additionally, there are dozens of hepatic enzymes that contribute to a complicated chain of events that eventually result in the breakdown of drugs (and other liver toxins).

Not everyone metabolizes drugs at the same rate. Different genetic and physiological characteristics can influence the speed at which an individual metabolizes a drug. A few influential factors are as follows:

  • Sex.
  • Age.
  • Inherited enzyme structure.
  • The flow of substances from the liver to the bile.
  • Microorganisms present in the gut.
  • Overall nutrition.

Certain medical conditions can slow drug metabolism. These include:

  • Kidney disease.
  • Shock (reduction in systemic blood flow).
  • Heart failure.
  • Liver disease.

Even different drugs themselves can alter the rate of metabolism; some drugs fall into the class of enzyme inducers, which boost metabolism, while others are classified as enzyme inhibitors, which reduce the speed in which a drug is broken down.

In many cases, the liver is able to metabolize drugs (and other toxins) without significant damage to the organ itself. However, when persistent detoxifying demands are made of the hepatic system – for example, when drugs are taken in excess, when the frequency of drug use is on the order of daily or hourly, or when multiple substances are consumed simultaneously – drugs can cause significant, cumulative damage to the liver.

Drug-Induced Liver Injury (DILI)

Drug-Induced Liver Injury (DILI) occurs when the consumption of a substance, such as a drug, nutritional supplement, medicinal herb, or plant, causes direct damage to the liver. In some cases, there might not be any symptoms, which can allow damage to go unnoticed. 3.

While some drugs, such as acetaminophen (also known as Tylenol), elicit predictable and dose-dependent effects on the liver, others may have unforeseeable results, oftentimes unrelated to dose 3. DILI typically occurs within three months of beginning the drug, but it can vary from a couple hours to a year after drug initiation 4.

Drug-Induced Hepatitis

One example of DILI is drug-induced hepatitis, which is characterized by inflammation of the liver 5. This condition can be caused by a number of different drugs. Below are just a few of the many medications that can cause drug-induced hepatitis 5:

  • Acetaminophen (often contained in fever reducers and painkillers like Percocet and Vicodin).
  • Nonsteroidal anti-inflammatory drugs:
    • Ibuprofen.
    • Naproxen.
    • Diclofenac.
  • Birth control pills.
  • Anabolic steroids.

These drugs, among others, can cause drug-induced hepatitis even in moderate doses. It’s important that you take your medication exactly as prescribed and avoid drinking alcohol while taking it 5.

If you have drug-induced hepatitis or any other drug-induced liver damage, your physician will likely tell you to stop taking the medication immediately 5. The symptoms usually dissipate once the individual stops taking the drug, although medical treatment may be necessary in cases of excessive acetaminophen consumption 5.

Factors that Raise Your Risk of DILI

A few risk factors that increase a person’s chance of experiencing drug-induced liver injury include 3, 6:

  • Drinking alcohol.
  • Being 18 years of age or older.
  • Genes that affect a user’s response to drugs.
  • Obesity.
  • Pregnancy.
  • Sex.
  • Other diseases, such as HIV or liver disease.
  • Illicit drug abuse.
  • Taking medication or drugs in excess.
  • Combining drugs and/or alcohol.

When your doctor prescribes you a medication that is known to cause liver damage, you will want to make sure to tell him or her what other medications you’re on in the case of possible drug interactions.

Alcohol and the Liver

When alcohol reaches the liver, it is broken down and excreted through the urine. This process produces many harmful by-products, such as free radicals and acetaldehyde, that may play a part in liver toxicity 8. If consumed in moderation, the liver typically has no problem with alcohol metabolism, but chronic and long-term alcohol abuse can lead to significant liver damage 8.

Two major conditions caused by excessive alcohol consumption are cirrhosis and alcoholic hepatitis.

Cirrhosis

Cirrhosis is characterized by scarring of the liver, which blocks the flow of bile and blood and inhibits proper functioning. The harm caused by cirrhosis of the liver is irreversible, but early detection can prevent further damage 9.

Some signs and symptoms of cirrhosis include 9:

Alcoholic Hepatitis

Alcoholic hepatitis, which is often seen in heavy drinkers, often co-occurs with cirrhosis 10 and is most often seen in people between the ages of 40 and 60-years-old 11. Alcoholic hepatitis is fatal in approximately 30-50% of those affected by the disease 11.

Some signs and symptoms of alcoholic hepatitis are 10:

  • Enlarged liver.
  • Fever.
  • Rapid heart rate.
  • Pain in right upper quadrant (abdominal region below right ribcage).
  • Jaundice.

Individuals with alcoholic hepatitis may have a variant of the disease called alcoholic steatohepatitis, which presents as pathological fat accumulation in the liver. It is caused by an increased production of fatty acids due to poor nutrition 12.

Severe forms of alcoholic hepatitis may lead to the following complications 10:

  • Portal hypertension (high blood pressure in the liver’s major vein).
  • Deficient clotting mechanisms leading to bleeding issues.
  • Kidney failure.
  • Hepatic encephalopathy (brain dysfunction due to liver damage and accumulation of toxins in the blood).

Individuals afflicted with alcoholic hepatitis are more vulnerable to infections, such as 10:

  • Tuberculosis.
  • Bacterial peritonitis.
  • Bacterial pneumonia.
  • Urinary tract infections

Although not actually caused by alcohol use, hepatitis C, which is an infection leading to liver inflammation 20, is very common among those who abuse alcohol 19. Chronic hepatitis C that goes untreated can lead to liver damage and liver cancer 20.

When combined with heavy alcohol intake, the amount of harm done to the liver is compounded 19. Those with hepatitis C that consume alcohol have an increased risk of developing liver disease and cirrhosis 19. For this reason, patients who are diagnosed with hepatitis C should abstain from drinking any alcohol.

Drugs that Can Damage the Liver

There are certain drugs and drug classes that have a higher likelihood of damaging the liver. These substances include 3, 5, 7:

Prescription Drugs

  • Antibiotics:
    • Erythromycin.
    • Amoxicillin-clavulanate.
    • Tetracyclines (doxycycline, minocycline, tetracycline).
  • Antipsychotic drugs:
    • Risperidone.
    • Chlorpromazine.
  • Statins (treats high cholesterol).

  • Antifungal drugs:
    • Terbinafine.
    • Ketaconazole.
  • Antihypertensives:
    • Lisinopril.
    • Captopril.
    • Methyldopa.
  • Halothane (anesthetic).
  • Birth control pills.
  • Antidepressants:
    • Setraline.
    • Fluoxetine.
    • Bupropion.
  • Anticonvulsants:
    • Phenobarbital.
    • Carbamazepine.
    • Phenytoin.

Other Drugs

  • Supplements and herbs (Can lack thorough testing and are not tightly regulated)
    • Comfrey tea.
    • Chaparral.
    • Skullcap.
    • Kava.
    • Excess vitamin A and iron.
    • Pyrrolizidine alkaloids.
    • Camellia sinensis (in black and green tea).
    • Pennyroyal oil (used in production of teas).
  • Over the counter pain-relievers:
    • Acetaminophen.
    • Nonsteroidal anti-inflammatory drugs:
      • Naproxen.
      • Ibuprofen.
  • Anabolic steroids.
  • Recreational and illicit drugs:
  • Heroin 13.
  • Inhalants 14.
  • Cocaine 15.
  • MDMA or Ecstasy 16.
  • Methamphetamine 17.

Symptoms of Liver Damage

If you or someone you love may be at risk of substance induced hepatic injury, it is vital that you be aware of the signs and symptoms of liver damage so that you can seek medical attention immediately.

Symptoms of liver damage include 5, 18:

  • Dark Urine.
  • Fever.
  • Pain in the abdomen.
  • Nausea.
  • Vomiting.
  • Headache.
  • Diarrhea.
  • White stools.
  • Rash.
  • Build-up of fluid in the abdominal cavity.
  • Jaundice (yellowing of eyes and skin).
  • Enlarged liver.
  • Fatigue.
  • Weight loss.
  • Loss of appetite.

Preventing Liver Damage

There are many different things you can do in order to prevent liver damage. Be mindful of the following tips 5, 7:

  • Don’t take more than the recommended dose of acetaminophen or other non-prescription medications.
  • Don’t take the maximum recommended dose for an extended period of time.
  • Follow your doctor’s prescribing instructions carefully.
  • Avoid drinking alcohol while taking medication.
  • Inform your physician of the drugs and supplements that you are currently taking.
  • If you suffer from liver disease, avoid taking drugs containing acetaminophen or phenytoin (Dilantin), and consult with your doctor about any other contraindicated pharmaceuticals.
  • If you abuse drugs or alcohol, seek addiction treatment to help you get clean.

Sources:

Last updated on November 23, 2018 2018-11-23T04:24:51+00:00 Finding the perfect treatment is only one phone call away!

Carl Grunfeld, MD, PhD —–

Anabolic steroid use causes decreased levels of HDL or “good” cholesterol, increased levels of LDL or “bad” cholesterol, and serious liver toxicity within 12 weeks, according to a study that measured the effects of anabolic steroids on men with HIV wasting disease.

The results have implications for athletes who take anabolic steroids to enhance performance, says principal investigator Carl Grunfeld, MD, PhD, chief of the metabolism and endocrine sections at the San Francisco VA Medical Center.

The study is published in the March 2006 issue of the Journal of Acquired Immune Deficiency Syndromes. It is available online in the “Publish Ahead of Print” section of the journal.

The researchers found that as expected, anabolic steroids lead to gains in both lean body mass and fat in men with HIV wasting.

“This is good news for people with devastating wasting illnesses, who suffer from the effects of loss of muscle mass and whose most immediate risk is that they will die of their disease,” observes Grunfeld. “But for people who aren’t this sick and who take anabolic steroids, there may be serious problems if these complications occur.”
Grunfeld, who is also a professor of medicine at the University of California, San Francisco, observes that “the biggest use of these steroids today is among body builders and athletes, who take these drugs to build muscle, but who could wind up with significantly damaged hearts and livers.”

The randomized, double-blind trial among 262 HIV-positive men was the largest study of its type on men with HIV-associated weight loss, according to the study authors.

For the first 12 weeks of the trial, the men were randomly assigned to receive daily doses of either 20, 40, or 80 milligrams of the anabolic steroid oxandrolone or a placebo. They were allowed to receive open-label oxandrolone for the second 12-week period.

Grunfeld says the adverse effects of the steroids were clear-cut within the first 12 weeks. “HDL plummets. LDL goes up. This predisposes people to an increased risk of heart attack. Furthermore, we found grade III and grade IV liver toxicity in some men, which means a very significant risk of serious liver damage.”
The men’s testosterone levels were also depressed. These effects were not seen in men taking placebo, according to Grunfeld.

The researchers observed that in men with the most wasting, the 20 milligram dose was more effective than higher doses in promoting weight gain. Subjects who weighed more and were healthier – and were therefore more like athletes who use the drugs, observes Grunfeld – required higher doses to gain weight. This is significant, he says, because it demonstrates in healthy people, “you need a higher dose to get a benefit – and the higher the dose, the more the toxicity.”

Based on observed changes in HDL and LDL, Grunfeld estimates that heart attack risk would be increased 58 percent among men taking 20 milligrams of oxandrolone per day, two-fold with a 40 milligram daily dose, and three-fold with 80 milligrams. “Add smoking or hypertension, and the risk becomes really serious,” he says.

The ability to promote gains in both muscle and fat makes these drugs unique among the medications used for HIV wasting disease, notes Grunfeld. He says that among patients with serious wasting illnesses, the benefits of immediate weight gain could still potentially outweigh the risks of longer-term heart and liver damage. For these patients, he says, it is important to have a store of fat as well as muscle mass, because “opportunistic infections burn up muscle if there’s no fat there. The more fat you have, the less muscle you burn.”

Nonetheless, he notes, “We would still stop the drug among anyone who has grade III or grade IV liver toxicity.”

Grunfeld, who has no further plans to study steroids, says he would like to see the current study validated in two future studies by other investigators. The first would look exclusively at the 20 milligram dose in patients with significant wasting, because “it may work and have less toxicity.” The second would investigate whether the same toxic effects occur in healthy individuals who take anabolic steroids.

Co-authors of the paper were Donald P. Kotler, MD, of St. Lukes Roosevelt Medical Center, New York; Adrian Dobs, MD, of Johns Hopkins School of Medicine, Baltimore; Marshal Glesby, MD, PhD, of the Community Research Initiative on AIDS, New York (at the time of the study); and Shalendar Bhasin, MD, of Charles Drew University of Medicine and Science, Los Angeles (at the time of the study).

The research was supported by a grant from Biotechnology General, Inc., now Savient Pharmaceuticals, Inc., makers of oxandrolone. In San Francisco, the grant was administered by the Northern California Institute for Research and Education.

UCSF is a leading university that consistently defines health care worldwide by conducting advanced biomedical research, educating graduate students in the life sciences, and providing complex patient care.

The mission of NCIRE is to improve the health and well-being of veterans and the general public by supporting a world-class biomedical research program conducted by the UCSF faculty at SFVAMC.

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