To Your Liver (hepatotoxicity)
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:
important nutrients from the food that you eat
necessary chemicals that your body needs to stay healthy
down harmful substances, like alcohol and other toxic
waste products from your blood
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.
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.
do anti-HIV drugs causes hepatotoxicity?
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
are actually two ways that anti-HIV meds can lead to
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:
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.
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.
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.
do I find out if my anti-HIV drugs are causing liver
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.
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.
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.
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.
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 :
or abdominal pain
of taste for cigarettes
you are experiencing any of these symptoms, it is very
important that you speak with your doctor or another
hepatotoxicity occur in everyone taking anti-HIV drugs?
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
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.
have HIV and hepatitis C. Does this mean that I can't
use anti-HIV medications?
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.
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.
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
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.
there any ways to effectively reverse or prevent hepatotoxicity?
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.
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.
the deal with alcohol?
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.
about my diet? Can I eat better to improve the health
of my liver?
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:
plentiful amounts of fruits and vegetables, especially
dark green leafy vegetables and orange and red colored
fruits and vegetables.
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.
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.
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.
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.
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.
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.
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
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:
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.
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.
A detoxifying agent found in beans, peas, lentils,
eggs, fish, garlic onions, seeds, and meat.
about nutritional supplements and herbs? My health-food
store stocks many products that claim to be good for
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.
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.
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.