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. It’s important to understand the ways in which medications can cause liver damage, the factors that can increase the risk of hepatotoxicity, 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 antiretroviral (ARV) drugs you are taking, do not be afraid to discuss them with your doctor.
How do HIV drugs cause liver damage?
Even though 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 two ways that HIV meds can lead to liver damage:
1. 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 (e.g., hepatitis C virus), abnormal chemical reactions can occur that can damage these cells. There are several ways in which this can happen:
- Taking a very high dose of a drug. If you were to swallow a high dose of an ARV drug or another medication (i.e., taking many pills when you are supposed to take one or two), 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. If you are allergic to a particular drug, your immune system can cause your liver to become inflamed as a result of interactions between key liver proteins and the drug. If the drug is not stopped, the inflammation can worsen and can cause serious damage to the liver. Two HIV drugs known to cause such allergic reactions (sometimes referred to as "hypersensitivity") in HIV-positive people are Ziagen (abacavir) and Viramune (nevirapine). 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-related symptoms (e.g., fever or a rash).
- Non-allergic liver damage. Some drugs can cause liver damage without an allergic reaction or use at high doses. Two particular HIV drugs that can cause serious liver damage, though in relatively small numbers of people, are Aptivus (tipranavir) and Prezista (darunavir).
2. Lactic Acidosis:
Nucleoside reverse transcriptase inhibitors (NRTIs) are not processed by they liver; they are removed from the bloodstream and from the body by the kidneys. Thus, many experts once speculated that these drugs would not likely cause damage to the liver. But, we now know that these drugs can damage "cellular mitochondria," the "powerhouses" inside cells that convert nutrients into energy. This can cause levels of lactate, a cellular waste product, to become elevated. If these levels become too high, a condition called lactic acidosis can occur, which can result in liver problems, including a buildup of fat in and around the liver and liver inflammation.
How do I find out if my HIV meds are causing liver damage?
The best indicator of hepatotoxicity 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 CD4 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 heal.
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 (e.g., AST above 43 IU/L but below 215 IU/L or ALT above 60 IU/L but below 300 IU/L), 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 lean to permanent liver damage and serious problems.
Fortunately, the vast majority of doctors order chem screens on a regular basis (every three to six months) and are usually able to catch mild-to-moderate hepatotoxicity (which is often reversible) before it progresses to severe hepatotoxicity. However, some drugs, such as Ziagen (abacavir) and Viramune (nevirapine), 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 you 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 (e.g., hepatitis B or hepatitis C). Symptoms of hepatitis include:
- anorexia (loss of appetite)
- malaise (feeling unwell)
- light-colored stools
- unusual tiredness/weakness
- stomach or abdominal pain
- jaundice (yellowing of the skin or whites of the eyes)
- 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.
What other factors increase the risk of hepatotoxicity?
- Being over 50 years of age
- Coinfected with hepatitis B and/or hepatitis C
- Taking other medication that can cause liver damage
- Alcohol or drug abuse
- Past history of liver damage
Can I take HIV meds if I have hepatitis B or C?
If you have chronic hepatitis C or hepatitis B—two viral infections that can cause the liver to become inflamed and damaged—you can take 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 HIV meds.
People living with HIV and hepatitis should watch out for liver enzyme increases during the first three months of Viramune (nevirapine) treatment as one study demonstrated increase risk of hepatotoxicity in those coinfected.
Extra caution is also suggested when people with HBV or HCV use either Aptivus or Prezista, especially if they have even moderate liver damage already.
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. To learn more about hepatitis C and its treatments, click here.
It is also important to monitor your liver carefully while taking ARV 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 hepatitis B or C, you can then monitor your levels closely while on treatment.
Are there ways to reverse or prevent hepatotoxicity?
If you have been told you that your ARV 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 drug(s), with a possible switch to new medications that are less likely to cause liver toxicity.
What else can I do to protect my liver?
Limit alcohol intake. 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 disease in people with hepatitis B and C. 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. Most physicians, however, recommend that people with more severe liver damage avoid alcohol. 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 medications, such as Flagyl (used to treat some parasitic infections), should not be combined with alcohol, and most experts advise staying away from alcohol completely if you have hepatitis.
Maintain a well-balance diet. 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 percent 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 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 vegetable oils (hydrogenated fats), deep-fried foods, foods that are not fresh 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 (must be fresh) 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.
- Avoid artificial chemicals and toxins such as insecticides, pesticides, artificial sweeteners (especially aspartame), and preservatives.
- 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 B12, 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 HIV medications.
- Be wary of raw fish (sushi) 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 wild mushrooms contain toxins that can cause serious damage to the liver.
- Be cautious of iron. Iron, a mineral found in meat and fortified cereals, can be toxic to the liver, especially in people who have hepatotoxicity or infections 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.
- 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 work by neutralizing highly reactive, destructive compounds called free radicals, which are produced in abundance by highly active organs (such as the liver, especially when it is processing drugs on a daily basis). 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, garlic and onions.
- A detoxifying agent found in beans, peas, lentils, eggs, fish, garlic, onions, seeds, and meat.
What about nutritional supplements and herbs?
Some complementary and alternative therapies (CAMS) have been suggested to help prevent or control liver damage. The complementary therapy that has been researched and used most frequently in liver disease is milk thistle (Sylibum marianum), but studies have yet to determine conclusively that it can prevent, halt or reverse liver damage in people with hepatitis. The National Center for Complementary and Alternative Medicine (NCCAM) at the National Institutes of Health (NIH) concludes that there is not sufficient evidence to recommend milk thistle for hepatitis C or other causes of liver damage. The HCV Advocate, an non-profit organization for people living with HCV, recommends that milk thistle is probably safe and that no one should be discouraged from using it, provided that they inform their provider that they are taking it, that they are aware of any possible drug interactions, and that they do not use it as a substitute for hepatitis C treatment.
N-acetyl-cysteine (NAC) is another CAM that is often used to treat liver toxicity from overdoses of acetaminophen (Tylenol). There are not, however, conclusive studies of NAC in treating other types of liver damage.
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. Some may interact with your HIV meds. Also, consumer protection groups who have done spot checks of various herbs and supplements have frequently found that herbs and supplements have either much less or much more of the active ingredients than stated on the bottles. Be sure to check with your health care provider before starting any complementary therapy.
Some herbs that have been associated with liver damage, and that the HCV Advocate recommends avoiding, include: Blue-green algae, borage (Borago officianalis), bupleurum, chaparral (Larrea tridentata), comfrey (Symphytum officinale and S. uplandicum), Dong Quai (Angelica polymorpha), germander (Eucrium chamaedrys), Jin Bu Huan (lycopodium serratum), kava, mistletoe (Phoradendron leucarpum and viscum album), pennyroyal (Mentha pulegium), sassafras (Sassafras albidum), shark cartilage, skullcap (Scutellaria lateriflora), and valerian. This list does not include every herb with known or suspected liver toxicities.
Last Revised: January 18, 2016