Liver disease
In the last in our three part series on the main threats to the health of
people with HIV, Tristan J Barber looks at liver disease
Your
liver is well worth looking after. Although you only have one, unlike other
organs, it has a unique ability to regenerate and can survive limited damage.
Liver disease has emerged as a key issue for people living with HIV. In the
early days of HIV, liver dysfunction in people with HIV was mainly linked
to opportunistic infections like cytomegalovirus; parasitic infections like
cryptosporidiosis and tumours like lymphoma and Kaposi’s sarcoma. There
was also drug-related hepatitis caused by septrin and other antibiotics.
All of these reflected severe immunodeficiency in people who, at that time,
had a very poor prognosis. Doctors had no other option but to treat the symptoms
and/or provide anti-infective or cancer therapies that had their own liver
side effects.
Changing liver problems
HAART (highly active antiretroviral therapy) changed all that. With fewer
deaths and opportunistic infections among people living with HIV there was
a corresponding change in the type of liver problems they experienced. The
liver is now one of the most important organs to consider when treating people
living with HIV.
Nowadays, liver disease a leading cause of illness and death in people living
with HIV. Several things can have an adverse effect on the liver:
• HIV drug side effects
• chronic hepatitis B and C infection
• excessive alcohol consumption can lead to liver diseases such as steatosis
or non-alcoholic steatohepatitis (NASH)
• recreational drugs also take their toll
By recognising and diagnosing liver problems early we can use HAART more safely
and effectively and increase people’s life expectancy. Nevertheless,
the complicated ways various diseases and drugs work can sometimes hinder
diagnosis and management of patients with liver abnormalities.
To find out if your liver is working properly doctors perform a liver function
test. A sample of blood is analysed for chemicals, such as enzymes and proteins,
that indicate if your liver is working well, being damaged and not performing
as well as it could be. This is quite common in people living with HIV, especially
those on HAART, and this makes it harder to work out the cause if your liver
function is elevated: is it the HIV drugs or is it a case of hepatitis?
How HIV drugs affect the liver
If you have just started a new HIV drug and your liver function tests show
higher than normal liver enzymes this usually suggests drug-related hepatitis.
This normally goes away once you stop taking the drug causing the problem.
Drug-related hepatitis can be a particular problem in some patients starting
therapy with nevirapine (Viramune). For this reason doctors are advised not
to start you on a regimen containing this drug if you are a woman with a CD4
count above 250 or a man with a CD4 count above 400. Apart from this, nevirapine
is well tolerated HIV drug and this sensible precaution helps doctors use
it even more safely in clinical practice.
Co-infection
Hepatitis B or C co-infection is common in people living with HIV (10 and
30 per cent, respectively) because the routes of transmission are similar.
Being co-infected with HIV and hepatitis does not seem to make your HIV progress
more rapidly, but having HIV does seem to increase the speed at which your
liver is damaged if you catch hepatitis, and without treatment the hepatitis
may develop into cirrhosis more quickly.
In positive people with hepatitis or liver damage it may be necessary to check
the levels of HIV drugs in your blood to prevent them putting extra stress
on you liver. This is called therapeutic drug level monitoring.
Experts are still debating whether it is better to treat HIV or hep C first
in people with both viruses. Wherever possible doctors avoid starting both
treatments at the same to reduce any toxic side effects people may experience.
To work out the precise cause of liver disease and extent of any damage to
the liver in co-infected people it may be necessary to perform a liver biopsy.
Some hospitals now use a machine called FibroScan instead. Like an ultrasound
scan it does not require you to have any needles stuck into your liver.
Fact box
Your liver is under your ribs on the right side of your body and is the largest
solid organ in the body, weighing in at around 1.5kg. It is heavier in men
than women and holds around 13 per cent (about a pint) of your total blood
supply at any given moment.
It is dark reddish brown and divided into two main parts called lobes (the
larger right and the smaller left), which are further subdivided into approximately
100,000 lobules. About 60 per cent of the liver is made up of liver cells
(hepatocytes) each with an average lifespan of 150 days. The liver receives
its blood supply via the hepatic artery and portal vein that transports nutrients
from the intestine or gut.
It has more than 500 functions, including:
• processing digested food from the gut and turning it into energy
• controlling levels of fats, proteins and glucose in the blood
• fighting infections
• clearing the blood of particles and infections including bacteria
• neutralising drugs and toxins
• manufacturing bile
• storing iron, vitamins and other essential chemicals
• manufacturing, breaking down and regulating numerous hormones including
sex hormones
• making enzymes and proteins responsible for most chemical reactions
in the body, eg those involved in blood clotting and tissue repair
Important functions
1. Producing quick energy
One of the liver’s functions is to break down and convert food into
energy when needed. Carbohydrates from our diet are broken down to glucose
and stored mainly in the liver and muscles as glycogen. When energy is needed
in an emergency the liver rapidly converts its store of glycogen back into
glucose ready for the body to use. People with liver damage may sometimes
lose the ability to control glucose concentration in the blood and need a
regular supply of sugar.
2. Getting rid of waste products
The liver helps the body get rid of waste products from the blood that aren’t
filtered out by the kidneys. Some of them pass into the bowel via the bile
duct.
3. Fighting infections
The liver plays a vital role in fighting infections, particularly those arising
in the bowel, by mobilising part of the body’s defence mechanism called
the macrophage system. The liver contains over half of the body’s supply
of macrophages that literally destroy any bacteria they come into contact
with. If your liver is damaged in any way its ability to fight infections
is impaired.
Hepatitis
Hepatitis literally means inflammation of the liver. Viruses are the most
common cause but there are others that are non-viral, such as too much alcohol,
the side effects of some drugs, both recreational and prescribed medicines.
There is also a disease called autoimmune hepatitis.
Viral hepatitis
The liver can be infected by an alphabet of viruses: hepatitis A, B, C, D,
E and possibly G. There isn’t a hepatitis F - so far. The main difference
between the viruses is how they are spread and the effects they have on your
health. Hepatitis A, B and C are the most common in the UK.
Hepatitis A
Caught by eating contaminated food or drinking water, usually in countries
where hygiene standards and sanitation are poor. There is a vaccine for this
virus.
Hepatitis B
This is mainly passed on by blood-to-blood contact (blood-borne) but can also
be caught through sex. Worldwide, hepatitis B kills between one and two million
people each year, yet there is a vaccine to prevent infection. Blood transfusions
have been screened in the UK since the 1970s. Hep B is considerably more infectious
than HIV.
Hepatitis C
Also blood-borne. Before September 1991, a few people were infected by contaminated
blood transfusions and blood products. Since then all blood donations have
been screened for the virus. In some, the route of infection is unknown but
in many others injecting drugs is the cause. Users are thought to become infected
by sharing injecting equipment. It takes just a tiny amount of blood from
someone who carries the virus to spread the infection if it gets into someone
else’s bloodstream.
Most people recover from hep A with no lasting liver damage but B and C can
cause long term liver disease, leading to cirrhosis and even liver cancer.
In many cases there are no early warning symptoms till liver damage is far
advanced.
Autoimmune hepatitis
This disease mainly affects women, usually just after the onset of puberty
or around menopause. It is thought to be caused by the body’s defence
system malfunctioning and attacking the liver. The most common symptom in
the early stages is fatigue and generally feeling unwell. However, the condition
can be controlled with drugs that work by dampening down the immune system’s
reaction to the liver.
Alcohol and the liver
Not everyone who drinks too much alcohol develops liver damage. It’s
still unclear why some do but there is evidence it could be due in part to
a combination of factors including genetic susceptibility. Consistent heavy
drinking can lead to what is known as a fatty liver; liver cells become engorged
with excess fat and inflamed (alcoholic hepatitis), or, most seriously, permanently
scarred and damaged (cirrhosis).
In general the more you drink, and the greater the frequency and duration
of heavy drinking, the more likely you are to develop cirrhosis.
The liver is an important organ that deals with a lot of insults. HIV and
HIV drugs, hepatitis viruses and treatments and consumption of alcohol and
recreational drugs all take their toll. Liver enzyme tests are part of routine
follow up of all patients with HIV and your doctor will be able to discuss
with you the significance of any change in your results.
It is well worth looking after your liver by eating a balanced diet, lowering
your alcohol intake and protecting yourself against other blood-borne viruses.
Tristan J Barber is a clinical research fellow at Imperial College London
and St Mary’s Hospital
