PI Perspective #24
April 1998 View PDF
Hepatitis in HIV Disease
Liver problems are a frequent cause of disease and sometimes death
in people with HIV. Technically, any significant irritation or inflammation
of the liver is called “hepatitis,” but the term is
more commonly used to refer to several infections of the liver.
The majority of such liver diseases in people with HIV are caused
by viruses, especially hepatitis B virus (HBV) and hepatitis C virus
(HCV). Other organisms that may cause liver disease include cytomegalovirus
(CMV), Epstein-Barr virus (EBV), mycobacterium avium complex (MAC),
toxoplasmosis and histoplasmosis. Studies have shown that almost
a quarter of people with HIV is also co-infected with HBV. Additionally,
many drugs used in the treatment of HIV disease can also cause forms
of liver disease or hepatitis as a side effect of their activity.
This article focuses on the most common forms of viral hepatitis—those
that are induced by an infectious agent. More than five types of
hepatitis (A-E) have been identified. Hepatitis A and E are mainly
transmitted through sexual contact while hepatitis B, C and D are
primarily spread through blood or other body fluids. This article
will deal primarily with hepatitis A, B and C. The symptoms of the
various hepatitis viruses are quite similar, with all causing elevated
levels of liver enzymes. Hepatitis A virus (HAV) most commonly causes
high fevers, jaundice (yellowing of the skin and eyes), nausea,
diarrhea, fatigue, abdominal pain, dark urine, vomiting and loss
of appetite. HBV most commonly causes fatigue, jaundice, vomiting,
abdominal pain, nausea and anorexia. HCV most commonly causes fever,
appetite loss, jaundice, nausea, diarrhea and vomiting. Diagnosis
of the various hepatitis viruses is usually done by a blood test.
It is important to get an accurate diagnosis so that sex partners
and people living in the same household can take appropriate preventative
measures. Recent advances have led to the development of technologies,
such as polymerase chain reaction (PCR) tests and branched DNA (bDNA),
to monitor hepatitis levels in blood. These are the same technologies
currently used to measure HIV RNA levels (viral load). Currently,
these tests are available for investigational use to measure HBV
and HCV levels.
Hepatitis A
Travelers who visit countries where HAV is common and sexually active
gay men are particularly at risk for developing hepatitis A. The
virus can be contracted through contact with infected people, by
drinking contaminated water or by eating contaminated food. Additionally,
gay men are most often infected through sexual contact, especially
through oral-anal contact with infected persons. A person is most
infectious about two weeks before the onset of jaundice. Although
HAV can be found in saliva, it is very unlikely that it can be transmitted
by saliva. HAV very rarely results in chronic liver disease.
Prevention
Hepatitis A can be easily prevented. Vaccination is the most effective
method of preventing HAV infections, however, maintaining good personal
hygiene, such as routinely washing hands, has also been shown to
be successful in interrupting outbreaks when the mode of transmission
is from person to person, including sexual contact. Hepatitis A
vaccines (Havrix and Vaqta) are 94–100% effective in preventing
HAV infection. An initial injection with the vaccine protects adults
for up to a year and a second booster shot is given 6–12 months
later. The second dose provides long-term protection against the
virus. Immune globulins (IG) are also sometimes used to prevent
hepatitis A. IG is over 85% effective in preventing HAV infection,
however, the period of protection is relatively short (usually between
three and six months depending on the dose of IG used).
Post Exposure Prevention to Hepatitis
People who have recently been exposed to HAV (household or sexual
contact with someone who has hepatitis A) should consider post exposure
prevention. People who have not been vaccinated against HAV should
receive IG within two weeks of exposure. People who were vaccinated
at least a month before exposure do not need IG.
Treatment
There are no treatments for hepatitis A. Most people clear the infection
on their own (without medication) and usually people will only develop
hepatitis A once. Therapies that may cause liver damage or which
are metabolized (broken down) in the liver should be used with caution.
Hepatitis B
Almost everybody is at risk for developing hepatitis B. This includes
health care workers, people who are sexually active, injection drug
users, people who require blood or blood products, prisoners, infants
born to mothers who are infected with HBV and people who have intimate
contacts or live with people with chronic HBV. Most cases of HBV
(30–60%) are believed to be sexually transmitted. Infection
with HBV virus often induces a temporary stage of acute infection
when a person feels seriously ill with fevers, liver pain and swelling
and severe fatigue. This period usually lasts from as little as
one week to as long as month, after which the patient recovers symptomatically.
However, some people go on to develop a chronic form of HBV infection.
Chronic HBV infection develops in up to 10% of people infected as
adults, which increases their risk of developing chronic liver disease
as well as transmitting HBV to others. Additionally, people who
are co-infected with HIV and HBV are more likely to develop chronic
HBV infection. Chronic HBV infection can take two general forms.
In most people who develop chronic HBV, the disease is largely benign
and without significant symptoms. It’s presence is detected
only through blood tests. In a small percentage of people, chronic
HBV takes an aggressive form, producing bouts of symptomatic illness.
Over time, this aggressive form of chronic HBV can lead to liver
failure and liver cancer. Regardless of which form chronic HBV takes,
chronic carriers are believe capable of transmitting the disease
to others.
Prevention
Vaccination is the most effective method of preventing hepatitis
B infection. However, most researchers recommend that gay men and
injection drug users be screened for hepatitis B antibodies (evidence
of previous HBV infection) before being given the vaccine. Hepatitis
B vaccine (Engerix-B and Recombivax HB) is usually given in a three
dose cycle. The first dose is about 50% protective, the second dose
85% protective and the third dose is typically 90% protective. The
second dose of the vaccine should be given at least one month after
the first and the third dose should be given at least 4 months after
the second dose. It is important to complete the entire regimen,
as the third dose is required to provide long-term protection. Some
studies suggests that people with HIV may not get the same response
to the vaccine as someone who is not infected with HIV. Therefore,
it is currently recommended that people with HIV who are vaccinated
check for hepatitis B surface antibody levels (an indicator of how
protective the vaccine might be) 1–2 months after the third
vaccine dose. People should consider revaccination with three more
doses if no or very low levels of antibodies are detected.
Post Exposure Prevention
People who have sexual contacts with someone who has acute hepatitis
B should receive hepatitis B immune globulin (HBIG) and hepatitis
B vaccine within 14 days after the most recent sexual contact. Adults
who live in the same household as someone with acute hepatitis B
are generally not at risk for infection. However, it is recommended
that children and adolescents be vaccinated against HBV. Furthermore,
if the person still has detectable hepatitis B surface antigen (a
marker of hepatitis B infection), then everyone in the household
should be vaccinated. Hepatitis B vaccine is currently recommended
to prevent HBV transmission for people with casual/household and
sexual contact with people who have chronic HBV infection.
Treatment
No treatment is approved for people with acute HBV infection. Interferon
alfa-2b (Intron A) is the only therapy currently approved for the
treatment of chronic hepatitis B. Studies have shown that it is
about 40% effective in eliminating chronic HBV infection, with people
who were infected during adulthood more likely to respond to this
treatment. Some studies suggest that people with HIV have a lower
response rate to interferon therapy than people who are not HIV
infected. Interferon alfa-2b is usually given three times a week
for 16 weeks or longer, subcutaneously (under the skin) or intramuscularly
(into the muscle). A significant number of people develop side effects
while on this therapy, with fevers, fatigue and headaches being
the most commonly reported.
Several therapies are currently being studied for the treatment
of HBV, including interferon alfa-2a (Roferon-A), interferon alfa
n3 (Alferon N), lamivudine (3TC, Epivir), famciclovir (Famvir),
lobucavir, thymosin alpha, adefovir dipovoxil (Preveon) and FTC.
Preliminary results have shown that lamivudine, famciclovir and
adefovir dipovoxil are all effective in reducing hepatitis B levels
(HBV DNA levels) in blood with some normalization in measures of
liver function.
Hepatitis C
Hepatitis C is mainly contracted through body fluids, primarily
blood or blood products, sharing needles, mother-to-child transmission
and through sexual contact. Only about 25% of people infected with
HCV develop symptoms after the initial infection. These symptoms,
usually flu-like such as fever, fatigue, muscle and joint pain,
nausea and vomiting, appear within 2–6 weeks after exposure.
Because the symptoms of HCV are usually milder than those of HAV
and HBV, they often go undiagnosed. Furthermore, because most people
infected with HCV do not have symptoms, they are more likely to
become chronic carriers of the virus and unknowingly infect others.
Chronic HCV develops in up to 85% of HCV infected people and about
70% develop some form of chronic liver disease. While the total
incidence of HCV is lower than that of HBV, it is spreading more
rapidly and the severity of the disease is far worse. For instance,
end stage HCV infection is now the leading indicator for liver transplantation
and chronic HCV also increases the risk of liver cancer. Recent
studies suggest that the course of HCV-related liver disease is
accelerated among people who are co-infected with HIV and HCV. Another
study found that people who were co-infected with HAV and HCV were
significantly more likely to die from sudden liver failure. Often
times, by the time HCV is diagnosed, the liver is already severely
damaged. The concurrent use of alcohol considerably increases the
risk of progression of liver disease. HCV, like HIV, is a very difficult
virus to treat because it can mutate quickly and develop many different
quasi-species (slightly different than the original virus) which
escapes the immune response.
Prevention
There is no effective vaccine against HCV. Because of the numerous
subtypes of HCV, the development of an effective vaccine is especially
difficult. Currently, the only method to prevent transmission of
HCV is to practice safe sex and to make sure that needles are sterilized
(this includes needles used for tattooing, body piercing and acupuncture).
Treatment
The only approved treatments for hepatitis C is interferon alfa-2b
and interferon alfa-2b. Since most people relapse after therapy
is stopped, treatment may need to be continued indefinitely. However,
the current recommendation is to use interferon alfa three times
a week for at least a year. There is also preliminary evidence that
treating acute hepatitis C may reduce the risk of developing chronic
disease. Some preliminary results also show that the combination
of interferon alfa-2b with ribavirin (Virazole and Rebetol) is more
effective than either drug alone. Preliminary results from other
studies have also shown that interferon alfa-n3 may be more effective
than interferon alfa-2a and -2b, while yet another interferon—consensus
interferon—shows promising activity. Because of the rapid
rate of mutation seen with HCV, it seem logical to expect that combination
therapy may be more effective and more durable than monotherapy.
Several studies have shown that people who are co-infected
with HIV and HCV have significantly higher HCV levels (HCV RNA levels)
than are seen in people who are infected with HCV alone. One small
study also showed that hepatitis C viral load levels temporarily
increased significantly after starting highly active antiretroviral
therapies (HAART). However, HCV levels returned to pre-HAART levels
after 17–32 weeks while continuing on HAART. The researchers
speculated that HAART results in a better immune response, destroying
more HCV infected liver cells, which could result in the release
of HCV particles. Many researchers are now measuring HCV levels
before initiating HAART and closely monitoring that level after
starting HAART as there have been a few reports of reactivation
of hepatitis C. Currently, there is no good data to guide physicians
in making treatment decisions for HCV based on HCV viral load, since
no long-term natural history studies have yet been conducted. What
constitutes a “high” or “low” HCV viral
load has not yet been determined, nor do we know how various viral
load levels correlate to outcomes of disease and death. Several
other therapies are being studied for the treatment of hepatitis
C including thymosin alpha, interferon beta, oral alpha interferon
and amantadine (a common flu drug).
Summary
A vaccine and treatments for hepatitis C are desperately needed.
An effective public health campaign needs to be implemented to alert
the public about the dangers of hepatitis, especially hepatitis
C. Since the route of transmission for HAV, HBV and HCV is similar
to that of HIV, many people are co-infected with these viruses.
It is important for people to find out whether they are co-infected
so that an appropriate treatment strategy can be put together. People
co-infected with HIV and HBV should talk to their physicians about
the various treatments for HBV and HIV. Some therapies are active
against both viruses. Combination therapy will likely result in
better activity against hepatitis B and hepatitis C. However, some
therapies may be broken down in the liver and may cause liver enzymes
to increase, potentially aggravating the hepatitis. On the other
hand, for someone who is HIV infected but not infected with HAV
or HBV, then vaccination should be considered.
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