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Liver Toxicity

Part of A Practical Guide to HIV Drug Side Effects

2006

Liver impairment in HIV disease is common and has many possible causes, only one of which are the medications you're taking. Many infections can result in liver damage, including:

  • co-infection with hepatitis viruses
  • opportunistic infections such as MAC (Mycobacterium avium complex), TB (tuberculosis), CMV (cytomegalovirus) or cryptosporidiosis

Other factors that may damage your liver to the point that it is operating at less-than-optimal function, even before infection with HIV, include:

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  • repeated use of antibiotics
  • excessive alcohol or recreational drug use
  • a nutrient-poor, chemically loaded diet

On top of that are the many HIV drugs which can also cause liver toxicity. The combination of all of these explains why a certain level of liver toxicity and dysfunction is a frequent occurrence in PHAs.

The liver uses enzymes to help it get rid of the waste produced in your body both by normal body processes and by the breakdown of drugs, alcohol and other toxins. When the liver is overly stressed by this waste or damaged by various infections, liver enzyme tests done on blood samples may show significantly elevated values. These liver enzyme tests include the following:

  • AST, also called SGOT (aspartate amino transferase)
  • ALT, also called SGPT (alanine amino transferase)
  • GGPT
  • AP (alkaline phosphatase)
  • LDH (lactic dehydrogenase)

All PHAs on HAART should have their liver enzymes monitored on a regular basis since liver damage is rarely something that is felt until it is quite advanced. It is especially important that people who already have some liver damage -- because of hepatitis, for example -- get regular blood tests for liver enzymes.

Bilirubin (a waste product) is also used as an indicator of liver disease. Note that some of these tests can be elevated by problems other than liver disease, so they must be interpreted carefully. However, even without elevations in these tests, there can be a level of less obvious liver dysfunction that should be addressed. Unfortunately, many people remain unaware of liver disease until it reaches a point that causes:

  • pain
  • swelling (hepatomegaly, or enlarged liver)
  • fever
  • jaundice (when the liver dysfunction results in an inability to break down bilirubin, which then causes yellowing of the skin and/or eyes)


Tips for Handling Liver Toxicity

Since a functional liver is critical for life, detoxifying and repairing it can be one of the most important things you do for your long-term health, especially if you want your liver to be able to handle HAART over the long-term. The most obvious first step in a liver repair program is to eliminate as many sources of toxicity as possible. You may not be able to eliminate your HAART meds, but the following steps can help a lot:

  • Try to cut out recreational drugs and decrease or, preferably, eliminate alcohol.
  • Make sure that you are vaccinated against hepatitis A and B.
  • Avoid situations that place you at risk for hepatitis C -- such as sharing needles (for drugs and tattoos) and nasal instruments used for cocaine and ketamine (sniffers, straws and bills).
  • Many doctors tend to prescribe antibiotics at the drop of a hat and this is not a good idea if you want to avoid damaging your liver. You should, of course, take them if you have a real need, but they shouldn't be used whimsically or for an infection like a cold or flu that's obviously viral, for which an antibiotic will do nothing.
  • Cut out chemically loaded junk foods and drinks, including caffeine (coffee and cola).
  • Decrease the fat content of your diet.
  • Check with your doctor and pharmacist to make sure that none of the supplements you are taking (particularly herbs) cause additional liver problems.

If you are taking meds that can cause liver toxicity, a careful review with your doctor should be done in order to determine if there are other meds that can be substituted for problematic ones.

A review of possible drug interactions should also be done. It is always possible that drugs that would normally cause no problems when taken alone might interact in a way that would cause significant toxicity. A "brown bag" checkup with your pharmacist to look at every single thing you're taking, whether it's by prescription or over-the-counter, is appropriate to check for all possible interactions.

An excellent website where you can check for drug/drug, drug/food and drug/herb interactions is www.aidsmeds.com.

Last, but certainly not least, any indication of liver damage should immediately prompt an assessment of the possibility of any infections or cancers that can damage the liver, including:

  • viral hepatitis
  • MAC
  • TB
  • CMV
  • cryptosporidiosis
  • lymphoma

When hepatitis B or C are present, treatment may be considered.

In addition to removing, as much as possible, anything that might be stressing the liver, it is very important to add the therapeutic agents that can help the liver to detoxify, repair and protect itself. There are a number of potentially useful agents, listed below:

Nutrients to Maintain Glutathione

Glutathione (GSH) is the most important intracellular antioxidant and is crucially important for protecting the liver against toxicity when it goes about its task of breaking down drugs and other toxins. Taking the following nutrients may help to maintain or increase levels of glutathione:

  • vitamin C (2-6 grams per day, in divided doses)
  • N-acetyl-cysteine, or NAC (500 mg, 3 times per day; always take with food because taking it on an empty stomach can cause gastrointestinal tract irritation)
  • L-glutamine (5 grams per day, increased up to 30-40 grams in those who also have diarrhea or wasting). Note that anyone with seriously compromised liver or kidney function should not take glutamine without a doctor's approval since it is an amino acid that must be processed by those organs.
  • alpha-lipoic acid, or thioctic acid (300-500 mg, twice daily; take on an empty stomach with fluids). Alpha-lipoic acid is a naturally occurring fatty acid that acts as a cellular coenzyme. It is very important to the liver cell metabolic pathways and can be rapidly depleted when the liver is under stress. It appears to help boost repair when there has been either virally induced or drug-induced liver damage. Note that alpha-lipoic acid disappears from the bloodstream very rapidly, so products made in an extended-release form will last longer and work better.

For anyone with liver dysfunction or disease, the above nutrients may be very important as part of a total treatment approach.

For people with fatty livers, another important nutrient is the amino acid carnitine. Researchers say that it may help prevent mitochondrial toxicity, thus helping the body to handle fat better. Early studies of its use for non-HAART-related elevated triglycerides in PHAs did, indeed, show successful lowering of the blood fat levels. Research in animals has shown its successful use in reversal of fatty livers. The usual dosage is two capsules (500 mg each) twice daily. The alternative is Carnitor, the basic form of carnitine, available by prescription only. It is usually prescribed in doses of 3,000 mg daily (three 330-mg capsules, 3 times daily). Too-high doses can cause diarrhea, so watch for this. Doses of plain carnitine need to be higher because the acetyl-L-carnitine releases four times as much free carnitine into the bloodstream, using equivalent doses.

Silymarin and Other Herbs

An herb called milk thistle (Silybum marianum) contains the compounds silybin, silycristin, silydianin and isosilybin, which, as a group, are commonly referred to as silymarin. Silymarin has powerful effects as both an antioxidant and protector of the liver. It protects healthy liver cells from toxic chemicals by promoting healthy cell membranes, and stimulates protein synthesis, which promotes new liver cell growth, thus repairing the liver where it is damaged. Specifically, it promotes repair and regeneration of liver cells through the anti-inflammatory silymarin flavonoids found in the plant. There are many herbal formulas available that contain silymarin in useful quantities. The suggested dosage for most of these is two capsules, three times per day, to be continued until liver enzymes return to normal; long-term use may help to continually protect and regenerate the liver. However, for those on HAART, it is important to know that silymarin may interact with some medications.

WARNING: Based on results of test-tube studies, milk thistle and compounds found in milk thistle, such as silymarin, may have the potential to affect levels of protease inhibitors and non-nucleoside analogues in the blood. Milk thistle and its extracts may also affect levels of other drugs that are processed by the liver. This action of milk thistle has the potential to cause side effects or weaken the activity of HIV drugs, causing them to not work effectively. One later study of milk thistle in people showed that most had only minor reductions in indinavir (Crixivan) levels. However, some caution is still required. For more info on the potential effects of milk thistle and sylimarin on medications, see the CATIE Supplement Sheet on milk thistle available at www.catie.ca/supple-e.nsf.

Glycyrrhizin

A licorice root extract known as glycyrrhizin has been shown in studies in Japan to reduce liver inflammation. It has been used for more than 40 years in Japan as a treatment for chronic liver disease and stomach ulcers. It should definitely not be taken if you have high blood pressure, low blood potassium or a weak heart or kidney problems. It can cause water retention and blood pressure increases that could be very serious. www.daair.org

For more info on liver health, see "13 Ways to Love Your Liver " in the spring/summer 2002 issue of CATIE's Positive Side magazine and "Me and My Liver" in the Spring/Summer 2005 issue, available at www.positiveside.ca or by calling 1.800.263.1638 [if you're in Canada].




  
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This article was provided by Canadian AIDS Treatment Information Exchange. Visit CATIE's Web site to find out more about their activities, publications and services.
 
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