Hepatitis B (cont.)
What medications are used to treat hepatitis B?
Acute infection
Acute infection with hepatitis B usually does not require treatment. In rare
cases, however, the infection may cause life-threatening liver failure. Patients
with liver failure due to acute hepatitis B should be evaluated for liver
transplantation. Small studies suggest that the drug
lamivudine (Epivir) may be effective
in this setting.
Chronic infection
If a person is chronically infected with hepatitis B and has few signs or
symptoms of complications, medications usually are not used. These patients are
watched carefully and given periodic blood tests. One test measures the 'viral
load,' that is, the amount of viral DNA in the blood. Doctors will recommend
treatment if there are signs that the virus is beginning to cause damage or if
the viral load is high. Another reason to prescribe medication is if the patient
has a positive test for the Hepatitis B e-antigen (HBeAg) in the blood. HBeAg is
associated with an increased risk of progression of liver disease and its
complications.
In chronic hepatitis B, the goal of treatment is to
reduce the risk of complications including cirrhosis and liver failure. However,
it takes decades for complications to occur, which makes it difficult to study
the effect of medications. As a substitute for waiting years to find out what
happens, scientists have used tests like the viral load or liver function tests
to evaluate if medicines are working. This is logical because it is known that
people who have large amounts of the virus in their blood are at highest risk to
get cirrhosis. Up to one-third of people with very high viral loads (more than
one million viral copies per milliliter of blood) will develop cirrhosis over a
decade, compared to only 4.5% of those with low viral loads (fewer than 300
viral copies per milliliter).
Medications can reduce the number of viruses in
the body and may be able to eliminate the virus from the bloodstream. Logically,
this should lead to them having a low rate of progression to cirrhosis (<1%
per year), although large, long-term studies have not been done. Even in people
who clear the virus from their blood, low numbers of viruses still live in the
liver and other cells. Thus, the medications do not cure the disease, but they can
prevent or delay complications and symptoms. People who have a good response to
treatment can still transmit the virus. Doctors follow blood tests that measure
viral load and liver function and they may recommend liver biopsies to evaluate if
the medications are working.
The medications in current use for chronic hepatitis B include the
interferons and nucleoside/nucleotide analogues. New agents are being developed
although they are still under investigation and considered experimental. There
are no accepted guidelines that tell how every patient should be treated. As a
result, treatment is individualized.
Interferon
Interferon-alpha has been used to treat hepatitis B for more than 20 years.
Interferon-alpha is a naturally occurring protein that is made in the body by
white blood cells to combat viral infections. In addition to its direct
anti-viral effects, interferon works against the hepatitis B virus by
stimulating the body's immune system to clear the virus. Compared to older
interferon alpha agents, pegylated interferon alpha, marketed as Pegasys or
Pegintron, has a more convenient dosing schedule, may be slightly more effective
and suppresses the virus for a longer period of time. Pegylated interferon alpha
is given once a week for 48 weeks.
- A significant reduction in the viral load or elimination
of detectable viral DNA from the blood occurs in two-thirds of persons during
treatment.
- Blood tests for liver functions normalize in approximately 40% people
treated with interferon.
- People who have significant abnormalities in liver
function before therapy are more likely to respond to treatment.
- Those who have normal liver
blood tests before treatment are less likely to respond to interferon therapy.
- Liver biopsy results show improvement in about one-third of patients.
Only
27%-32% of persons who have Hepatitis B e-antigen (HBeAg) in their blood will be
able to eliminate HBeAg and produce antibodies against the HBe antigen after
treatment with interferon. Relapse may occur after treatment is stopped.
Sustained response (undetectable viral load in the blood, normal liver function
tests) occurs in approximately 15% to 30% of patients after the drug is stopped.
Although this is not a cure (some virus still lives in the liver and elsewhere),
people with sustained response are at low risk for complications of liver
disease. If the responder's immune system is compromised, for example through
the use of steroids or acquiring HIV, the disease can recur. Periodic monitoring
of blood tests can help confirm that the response continues to be sustained.
Interferon side effects
Interferon causes several side effects including:
- fatigue, generalized muscle
aches, fever, chills and
loss of appetite. These flu-like symptoms occur in approximately 80% of
treated patients;
- mood swings, depression,
anxiety and other
neuropsychiatric effects may occur; and
- thyroid gland abnormalities resulting in
hypothyroidism (too little
thyroid hormone);
- significant suppression of the
bone marrow and
production of blood cells;
- infection;
- or hair loss may occur.
The side effects may be severe enough that the patient is unable to continue
treatment. During treatment, the normal immune response to the virus is
stimulated and may cause worsening inflammation in the liver. This is normally a
good sign showing that the interferon is working, but more extreme responses may
in rare cases cause liver failure. Thus, physicians will monitor blood tests
closely during therapy. Persons with unstable liver disease due to cirrhosis
usually should not take interferon because of the increased risk of liver
failure.
Nucleoside/nucleotide analogues
Nucleoside/nucleotide analogues (NAs) are man-made chemicals that mimic the
nucleosides and nucleotides that are used for making DNA. When the virus tries
to use the analogues to make its own DNA, it is unable to make the DNA and,
therefore, cannot reproduce. Examples of these agents include
adefovir
(Hepsera), entecavir (Baraclude),
lamivudine (Epivir-HBV, Heptovir, Heptodin),
telbivudine (Tyzeka) and tenofovir (Viread).
- In patients who have HBeAg in their blood, NAs reduce the
viral load, causing the virus to become undetectable in 21% to 67% of patients.
- Normalization of blood liver tests occurs in 40% to 77%, and loss of HBeAg
occurs in approximately 12% to 22% of cases after one year of treatment.
- Results
are better in patients who do not have HBeAg in their blood, with 50% to 90%
having non-detectable virus and 60% to 80% having normalization of liver
function tests.
In a 2004 study in people who already had cirrhosis from
hepatitis B, treatment with lamivudine cut the risk of liver cancer and
progressive liver
failure by more than 50%. Newer NAs such as entecavir (Baraclude) and telbivudine
(Tyzeka) appear to
have higher response rates than older agents such as lamivudine (Epivir-HBV,
Heptovir, Heptodin), but there is less
experience with these NAs.
Unfortunately, the hepatitis B virus may become resistant to NAs over time
(see below). Adefovir may be effective against strains of virus that have become
resistant to lamivudine and may be added to lamivudine when resistance appears.
Simply switching from one NA to another is not recommended because this leads to
virus strains that are resistant to multiple medications.
Currently, the optimal duration of treatment with nucleoside/nucleotide
analogues is uncertain. Persons with HBeAg may be treated until six months after
the HBeAg disappears from the blood and is replaced by antibodies (anti-HBe), if
this occurs. In persons without HBeAg, the endpoints are less clear. Some
experts advocate treating until the viral load (viral DNA) is undetectable and
the surface antigen (HbsAg) has been cleared from the blood. Others suggest
continuing medications for prolonged periods to suppress the virus. All of these
strategies are hampered by the risk of the virus becoming resistant to the
medications. Patients who discontinue treatment with NAs should be monitored
carefully for recurrent hepatitis, which may be severe.
Why does hepatitis B virus become resistant to nucleoside/nucleotide
analogues?
The major challenge associated with long-term therapy with NAs is the
development of viral resistance to the NAs. This resistance results from a
change (mutation) in the genetic material of the virus.
- For lamivudine (Epivir-HBV, Heptovir, Heptodin), the
incidence of resistance is 25% after one year and as high as 50% after three
years of treatment.
- With telbivudine (Tyzeka), resistance rates are 5% to 11% after one
year.
Therefore, some guidelines do not recommended lamivudine or telbivudine
alone as the first treatment for chronic hepatitis B.
For other NAs such as adefovir (Hepsera), resistance is less common after one year of
therapy but rises to 30% after five years. Early results with entecavir
(Baraclude) suggest
that resistance may be uncommon with this agent. When resistance occurs, the
viral load may rise or blood liver tests may become abnormal.
Is there a preferred treatment for chronic hepatitis B?
There are no clear guidelines to recommend which agent to use first in
treating chronic hepatitis B. Interferon is given for a defined period of time
and may have a more prolonged response after the medication is discontinued than
NAs. However, interferon is given as an injection, and side effects often are
troublesome. NAs are given as a pill and have few side effects, but the duration
of treatment is unclear, and prolonged therapy may be required. NAs may be
preferred in patients with unstable disease and cirrhosis because they are
thought to be less likely to cause serious flares of hepatitis with more severe
liver disease.
Next: What are the effects of alcohol on hepatitis B? »
- interferon - Describes the medication interferon (Roferon-A, Intron-A, Rebetron, Alferon-N, Peg-Intron, Avonex, Betaseron, Infergen, Actimmune, Pegasys), a drug used in managing many diseases that involve the immune system.
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