Risks To Your Liver (hepatotoxicity)

Introduction

The liver is one of the largest and most important organs in the human body. It is located behind the lower right section of your ribs and carries out numerous functions that your body requires to remain healthy. These are just a few of the liver's many functions:

• Storing important nutrients from the food that you eat
• Building necessary chemicals that your body needs to stay healthy
• Breaking down harmful substances, like alcohol and other toxic chemicals
• Removing waste products from your blood

For HIV-positive people, the liver is of major importance, as it is responsible for making new proteins needed by the immune system, helps the body to resist infection, and processes many of the drugs used to treat HIV and AIDS-related infections. Unfortunately, these same medications can also damage the liver, which can prevent the liver from performing all of its necessary tasks and can eventually cause damage to the liver.

"Hepatotoxicity" is the official term for liver damage caused by medications and other chemicals. This lesson has been prepared by the staff to help readers better understand hepatotoxcity, including the ways in which medications can cause liver damage, the factors that can increase the risk of hepatotoxcity, and some of the ways in which you can monitor and protect the health of your liver. If you have questions or concerns about hepatotoxicity, particularly as it relates to the anti-HIV drugs you are taking, do not be afraid to discuss them with your doctor.

How do anti-HIV drugs causes hepatotoxicity?

Even though anti-HIV drugs are intended to do your health good, the liver recognizes these medications as toxic compounds. After all, they are not naturally produced by the body and do contain some chemicals that could potentially cause damage to your body. Working with the kidneys and other organs, the liver processes these drugs to render them safer. In the process, the liver can become "overworked," which can lead to liver damage.

There are actually two ways that anti-HIV meds can lead to liver damage:

Direct damage to liver cells:
Liver cells, called hepatocytes, play a vital role in the functioning of the liver. If these cells begin working too hard to remove chemicals from the blood, or if they are harmed by other infections, abnormal chemical reactions can occur that can damage these cells. There are actually three ways in which this can happen:

• Taking a very high dose of a drug. If you were to swallow a high dose of an anti-HIV drug or another medication, this can cause immediate and sometimes severe damage to liver cells. Almost any drug, if an overdose is taken, can cause this type of liver damage.
• Taking standard doses of medication for a long period of time. If you take medications on a regular basis for a long period of time, there is also a risk of damage to these liver cells. This usually occurs after several months or years of taking certain medications. Protease inhibitors have the ability to cause damage to liver cells if they are used for long periods of time.
• An allergic reaction. When we hear the term "allergic reaction," we often think of itchy skin or runny eyes. However, allergic reactions can also take place in the liver. If you are allergic to a particular drug, your immune system can cause your liver to become inflamed as a result or interactions between very liver proteins and the drug. If the drug is not stopped, the inflammation can worsen and can cause serious damage to the liver. Two anti-HIV drugs known to cause such allergic reactions in HIV-positive people are Ziagen and Viramune. Allergic reactions such as these usually occur within a few weeks or months after the drug is started and either may or may not be accompanied by other allergy-repeated symptoms.

How do I find out if my anti-HIV drugs are causing liver damage?

The best indicator o fhepatotoxicity is an increase in certain liver enzymes that circulate in the bloodstream. The most important enzymes are AST (aspartate aminotransferase), ALT (alanine aminotransferase), alkaline phosphotase, and bilirubin. These four enzymes are normally checked as a part of a "chem screen," a panel of tests that your doctor probably orders every time you have blood drawn to check your T-cells and viral load.

If you or your doctor has any reason to suspect that a drug you are taking has been causing liver injury, then a blood test should be performed, it is always best to detect hepatotoxicity in its early stages so that steps can be taken to prevent it from getting worse and to allow the liver to heat.

Most of the time, hepatotoxicity takes several months or years to develop and usually begins with mild increases in either AST or ALT that progresses to more serious increases. Generally speaking, if your AST or ALT levels are elevated but are no higher than five times the normal range, you have mild to moderate hepatotoxicity. If your AST is higher than 215 IU/L or your ALT is above 300 IU/L, you have severe hepatotoxicity, which can learn to permanent liver damage and serious problems.

Fortunately, as stated above, the vast majority of doctors order chem screens on a regular basis and are usually able to catch mild-to-moderate hepatotoxicity before it progresses to severe hepatotoxicity. However, some drugs, such as Ziagen and Viramune, can result in an allergic reaction in the liver that can cause liver enzymes to increase sharply soon after the medication is started. In turn, it is very important that your doctor check your liver enzymes every two weeks for the first three months if your begin taking either of these medications.

Increased liver enzymes can rarely be felt. In other words, you may not have any physical symptoms, even if your liver enzymes are elevated. Thus, it is very important that you and your doctor monitor your liver enzymes on a regular basis using blood tests. However, symptoms can occur in people with severe hepatotoxicity and these symptoms are very similar to those associated with viral hepatitis. Symptoms of hepatitis include :

• Anorexia
• Malaise
• Nausea
• Vomiting
• Light-colored stools
• Unusual tiredness/weakness
• Stomach or abdominal pain
• Jaundice
• Loss of taste for cigarettes

If you are experiencing any of these symptoms, it is very important that you speak with your doctor or another health-care provider.

Does hepatotoxicity occur in everyone taking anti-HIV drugs?

No, it does not. There have been a number of studies looking at the percentage of patients who develop hepatotoxicity, according to the different anti-HIV medications they are taking. One particular study, conducted by researches at the National Institute of Health, looked at rates a hepatotoxicity among 10,611 HIV-positive people participating in 21 government-funded clinical trials conducted between 1991 and 2000. Overall, 6.2% of the clinical trial participants experienced severe hepatotoxicity. Among the participants who took a non -nucleoside reverse transcriptase inhibitor in combination with two nucleoside analogues, severe hepatotoxicity occurred in 8.2%. Among the participants who took a protease inhibitor in combination with two nucleoside analogues, severe hepatotoxicity occurred in 5%.

Unfortunately, clinical trials do not always reflect what is going to happen in the real world. Many clinical trials only follow participants for a year - and we know that HIV positive people will need to take these medications for many years, which can increase the risk of hepatotoxicity. What's more, most clinical trials enroll patients who don't have other conditions that can further increase the risk of hepatotoxicity. For example, it is believed that women and people over the age of 50 are at a higher risk of developing hepatotoxicity. Obesity and heavy alcohol use can also increase the chances of hepatotoxicity occurring. There is also a very real concern that HIV-positive people who are coinfected with hepatitis B or hepatitis C are more likely to experience hepatotoxicity than those who are city infected with HIV.

I have HIV and hepatitis C. Does this mean that I can't use anti-HIV medications?

No. Just because you have chronic hepatitis C or hepatitis B - two viral infections that can cause the liver to become inflamed and damaged - does not mean that you cannot take anti-HIV medications. However, it is important to understand that there may be a higher risk of liver damage occurring if you have either of these infections and are taking and HIV medications.

While there have been a number of studies looking at rates of hepatotoxicity among people coinfected with both HIV and hepatitis C or hepatitis B who are taking anti-HIV medications, the results often conflict with one another. For example, one study conducted by the San Francisco Community Health Network demonstrated that Viramune was the only anti-HIV medication to significantly increase the risk of hepatotoxicity in people connected with HIV and either hep C or hep B. But have also been study results suggesting that Viramune is no more or less likely to cause hepatotoxicity in coinfected patients than other anti-HIV medications, although it's still important to watch out for liver enzyme increases during the first three months of Viramune treatment.

As for the protease inhibitors, there have been a few studies demonstrating that Norvir is the most likely to cause hepatotoxicity in HIV positive people coinfected with hep C or hep B. However, Norvir is rarely used at the approved dose - much lower doses of Novir are usually used, as it is now most frequently prescribe to boost other protease inhibitor levels in the bloodstream. This, in turn, likely decreases the risk of hepatotoxicity in people who are only infected with HIV or coinfected with HIV and either hep C or hep B.
If one thing is clear, it is that people who are coinfected with HIV and either hep C or hep B should work closely with their doctors to come up with safe and effective treatment plans. For example, many experts now believe that, if you have HIV and hep C. you should consider starting hep C treatment while your T-cell counts are high, before treatment is needed for HIV. Successfully treating or controlling HCV is perhaps, the best way to reduce the risk of hepatotoxicity once anti-HIV medications are started.

It is also important to monitor your liver carefully while taking anti-HIV medications. You'll want to find out the levels of your liver enzymes before you begin taking anti-HIV medications. Even if they are higher than normal because of either hep C or hep B, you can then monitor your levels closely while on treatment.

Are there any ways to effectively reverse or prevent hepatotoxicity?

If you have been told you that your anti-HIV medications are causing liver toxicity, you and your doctor will likely want to figure out which drug - or which combination of drugs - are causing your liver enzymes to increase. Working together, you and your doctor can then determine if it's necessary to stop the offending drugs, with a possible switch to new medications that ar eless likely to cause liver toxicity.

Fortunately, taking proper care of your liver is not limited to avoiding or switching certain anti-HIV medications. The next few sections of this lesson review some of the most important things that you can do protect your liver while you are taking anti-HIV medications.

What's the deal with alcohol?

There's no shortage of information concluding that heavy alcohol use - generally defined as more than five drinks a day - can cause liver damage. It's also known that heavy alcohol use can worsen liver diseases in people with hep C and hep B. Although it's still not known if light or moderate drinking - no more than one to two drinks a day - is harmful to the liver, especially in people taking medications on a regular basis. If you drink alcohol, it is very important that you discuss this with your doctor. It's also important to note that the American Liver Association recommends no more than one drink a day. Some medicators, such as Flagy, should not be combined with alcohol, and most experts advise staying away from alcohol completely if you have hepatitis.

What about my diet? Can I eat better to improve the health of my liver?

Yes, absolutely. The liver is not only responsible for processing medications-it must also process and detoxify the liquids and foods we drink and eat on a daily basis. In fact, between 85%and 90% of the blood that leaves the stomach and intestines contains nutrients from the liquids and foods we consume for further processing by the liver. As a result, a well-balanced diet is a terrific way to help take some of the stress off the liver and to help it remain healthy. Here are some tips to consider:

• Eat plentiful amounts of fruits and vegetables, especially dark green leafy vegetables and orange and red colored fruits and vegetables.
• Cut down on fats that may put a lot of stress on the liver, such as dairy products, processed vegetables oils, deep fried foods that are not fresh and contain and contain rancid fats, preserved meats and fatty meats.
• Concentrate on eating "good fats" which contain essential fatty acids. These are found in cold pressed vegetable and seed oils, avocados, fish, flaxseed, raw nuts and seeds and legumes. Not only are good fats believed to be easier for the liver to process, they can help build healthy cell membranes around the liver cells.
• Do your best to avoid artificial chemicals and toxins such as insecticides, pesticides, artificial sweeteners, and preservatives. You should also be careful regarding the coffee you drink. Many nutritionists recommend no more than two cups a day and should be brewed from ground natural coffee, not instant coffee powders.
• Consume a diverse range of proteins from grains, raw nuts, seeds, legumes, eggs, seafood, and if desired, free range chicken and lean fresh red meats. If you are a vegetarian, you may want to consider supplements such as vitamin B 12, taurine, and carnitine to avoid poor metabolism and fatigue.
• Drink large amounts of fluids, especially water. Drinking at least eight glasses of water a day is a must, especially if you're taking anti-HIV medications.
• Be wary of raw fish or shellfish. Sushi can harbor bacteria that may harm the liver and shellfish can contain the hepatitis A virus, which can cause serious liver problems in people who have not received the hepatitis A vaccine. Also take care to avoid wild mushrooms. Many types of wid mushrooms contain toxins that can cause serious damage to the liver.
• Be cautious of iron. Iron, a mineral found in mean and fortified cereals, can be toxic to the liver, especially in people who have hepatotoxicity or infection that can cause hepatitis. Foods and cooking equipment - such as iron skillets - high in iron should be used sparingly.

There are a number of vitamins and minerals that have been shown to be healthful to the liver and many nutrition experts recommend that people at risk for liver toxicity seek out these foods at the grocery market. These include:

• Vitamin K. Green leafy vegetables and alfalfa sprouts are a great source of this vitamin.
• Arginine. The liver can sometimes have a difficult time processing protein. This can cause ammonia levels to increase in the bloodstream. Arginine, which is found in beans, peas, lentils, and seeds, can help detoxify ammonia.
• Antioxidants. Antioxidants work by neutralizing highly reactive, destructive compounds called free radicals, which are produced in abundance by highly active organs. Foods high in antioxidants include vegetables and fruits like carrots, celery, beets, dandelion, apples, pears, and citrus. Selenium, a powerful antioxidant, can be found in brazil nuts, brewers yeast, kelp, brown rice, liver, molasses, seafood, wheatgerm, whole-grains, gralic and onions.
• Methionine. A detoxifying agent found in beans, peas, lentils, eggs, fish, garlic onions, seeds, and meat.

What about nutritional supplements and herbs? My health-food store stocks many products that claim to be good for the liver.

Some complementary therapies that have been suggested to help prevent or control liver damage include thioctic acid, SSKT, coenzyme Q-10, glycerrhizin, milk thistle, NAC. Astragalus, chickory, dandelion, centaury. American mandrake, and celandine.

Unfortunately, there is not much research data to conclude that these complementary therapies are both safe and effective for either the prevention or treatment of hepatotoxicity or liver damage caused by infections. Some studies have suggested that milk thistle, a popular liver-health supplement, is safe for people to use. We also know that NAC is used throughout Europe and the United States to help reduce liver damage caused by acetanminophen.

It is important to remember that simply because these complementary therapies can be purchased without a prescription, this does not mean that they are always safe to take. Some complementary therapies have their own side effects. It's also clear that many complementary therapies can interact with certain anti-HIV medications. This can further increase the risk of side effects or, quite possibly, reduce the effectiveness of the anti-HIV medications begin used. Be sure to check with your health care provider before starting nay complementary therapy.