Hepatitis B Virus:
Hepatitis B Virus in
Various Body Fluids
Who should be tested?
Chronic hepatitis B
FOR HEPATITIS B AND C
Hepatitis B Blood test
Hepatitis E (HEV)
เชื้อไวรัสตับอักเสบบี พบได้ในสารน้ำและสารคัดหลั่งต่างๆ ของร่างกาย ได้แก่ เลือด น้ำลาย น้ำนม น้ำอสุจิ
และเมือกในช่องคลอด จึงติดต่อถึงกันได้ทางเข็มฉีดยา หรือของมีคมที่เปื้อนเลือด ทางเพศสัมพันธ์
อาการเริ่มแรกไม่ชัดเจน ไม่รวดเร็ว จะมีไข้ต่ำๆ หรืออาจไม่มี ต่อมาไข้สูง อ่อนเพลีย คลื่นไส้ อาเจียน และค่อยๆ
ตัวเหลือง ตาเหลือง และเป็นดีซ่าน บางรายไม่มีอาการแสดงให้เห็น กว่าจะรู้ตัวเป็นตับแข็งแล้ว
โรคตับอักเสบเรื้อรังอาจมีอาการอื่นร่วมอยู่ด้วย เช่น ปวดข้อ หรือไตอักเสบ
หายสนิท ส่วนน้อยที่จะมีความรุนแรงของโรคถึงแก่ชีวิต หรือทุเลาแล้วกลับรุนแรงขึ้นอีก
เป็นพาหนะเรื้อรัง โดยไม่แสดงอาการเจ็บป่วย แต่สะสมเชื้อไว้ภายในร่างกาย
1. กรณีเป็นโรคชนิดเฉียบพลัน ไม่มีภาวะแทรกซ้อน ให้ผู้ป่วยพักผ่อนประมาณ 4 สัปดาห์
หลังหายป่วยแล้ว 2-3 เดือน หลีกเลี่ยงอาหารและการกินสารที่เป็นพิษต่อตับ และรักษาโรคตามอาการ
2. กรณีมีภาวะแทรกซ้อน แพทย์จะพิจารณารักษาเป็นรายๆ ไป
3. ผู้ปว่ยโรคตับอักเสบเรื้อรัง ให้รักษาตามอาการ อยู่ในความดูแลของแพทย์
4. ผู้เป็นพาหนะเรื้อรังไม่มีอาการ ให้ตรวจร่างกายเป็นประจำตามแพทย์สั่ง แนะนำให้นำบุตรหลาน
1. บุคคลทั่วไป ป้องกันตนเองมิให้ติดโรคนี้ได้โดย ไม่ใช้เข็มฉีดยาร่วมกับผู้ป่วย
เพศสัมพันธ์ ตรวจเลือด หากไม่มีภูมิคุ้มกันให้ฉีดวัคซีนป้องกันโรค
2. ทารกแรกเกิด ที่มารดาเป็นโรคหรือเป็นพาหนะ
Hepatitis B: A Brief History:
In 1965, Dr. Blumberg who was
studying haemophilia, found an antibody in two patients which reacted
against an antigen from an Australian Aborigine. Later the antigen was
found in patients with serum type hepatitis and was initially designated
"Australian Antigen". Subsequent study has shown the Australia
Antigen to be the hepatitis B surface antigen. Dr. Blumberg was
subsequently awarded the Nobel Prize for his discovery. Initially there
appeared to be three particles associated with hepatitis B infection: a
large "complete" particle called the "Dane
particle", a small circular 20nm particle and an oblong 40nm
particle. Further research identified the Dane particle as the hepatitis
B viron and the other two particles as excess surface protein. This
former terminology is no longer used and the virus is referred to
according to its structure.
Hepatitis B Virus: A Complex
The hepatitis B viron consists of
a surface and a core. The core contains a DNA polymerase and the e
antigen. The DNA structure is double stranded and circular. There are
four major polypeptide reading frames (genes): the S (surface), the C
(core), the P (polymerase) and the X (transcriptional transactivating).
The S gene consists of three regions, the pre-S1, pre-S2 and encodes the
surface proteins (HBsAg). Very rarely a mutation may occur in the S gene
and may abort the HBsAg with the result that a person may be HBsAg
negative but still have virus present as determined by HBV DNA. The C
gene is divided into two regions, the pre-core and the core, and codes
for two different proteins, the Core antigen (HBcAg) and the e antigen (HBeAg).
A not uncommon mutant is the pre-core mutant, which may stop production
of HBeAg, and these persons will be HBsAg positive, HBV DNA positive,
but HBeAg negative. A third mutant which appears to have a mutant in the
core has been described and is referred to as HBV2. These patients are
HBsAg positive, but lack HBeAg and HBV DNA, thus also anti-HBc. Another
mutant, the YMDD mutant, will be described at a later date.
To make it even more complex, the
HBsAg particles are antigenically complex and these antigenic
determinants have been identified. There is a single common determinant
designated a, and four major subdeterminants designated d,y,w and r.
Thus, the four major determinants are: adw, adr, ayw and ayr.
Multiple Tests are Available
Because of the complexity and the
antigenic differences of the virus, there are a number of tests
available for hepatitis B:
HBsAg = presence of the virus
HBcAg = not detected in blood
HBeAg = correlates with the viral replication and infectivity
anti-HBs = antibodies to the surface
anti-HBc = antibodies to the core can be either IgM (acute) or IgG
anti-HBe = antibodies to e and indicates low infectivity and probable
HBV DNA = indicates virus presence and activity
DNA polymerase = determines the presence of HBV DNA
HBsAg in liver cells (Orcein stain = Shakata cells) = HBsAg inside
Hep B:The Complexities
Carrier Rates Vary Greatly
Carrier rates for hepatitis B
Country and Carrier rate%:
Hepatitis B DNA is found in many
body fluids including saliva, urine, semen and menstrual blood. It has
also been shown that the virus can be transmitted by ingesting
contaminated blood. Hence, hepatitis B may be transmitted by:
- mother to infant at the time
- horizontally through shared utensils such as razors, toothbrushes,
- through unsterile instruments such as tattoo needles, dental
- parenteral drug use through shared needles, syringes, etc.
- hospital staff through needle prick
- blood sucking arthropods (usually in the tropics)
Although uncommon, a number of
conditions associated with hepatitis B antigen/antibody complexes have
been recognized. These include:
Polyarteritis - usually involves
medium and small arteries, appears early
Glomerulonephritis - largely in children, liver disease is usually mild
Polymyalgia rheumatica - usually in older persons
Essential mixed cryoglobulinemia - sometimes only a test tube finding
of Hepatitis B Virus in Various Body Fluids
HBV is transmitted by percutaneous or permucosal exposure to infectious
blood or body fluids from persons who have either acute or chronic HBV
infection. The highest concentrations of virus are in blood and serous
fluids; lower concentrations are found in semen, vaginal fluid, and
saliva. Therefore, blood exposure and sex contact are relatively
efficient modes of transmission. Saliva can be a vehicle of transmission
through bites; however, transmission has not been documented to occur as
a result of other types of exposure to saliva, including kissing. HBsAg
has also been detected in low concentrations in other body fluids,
including tears, sweat, urine, feces, breast milk, cerebrospinal fluid,
and synovial fluid; however, these fluids have not been associated with
This original paper
was written by Dr. Florence Wong,
Gastroenterologist at The Toronto Hospital in Ontario, Canada.
Hepatitis B is a virus that infects the liver. Is estimated
that 350 million people are infected with hepatitis B worldwide,
with 50 million new cases diagnosed annually. The carrier rate of
hepatitis B varies widely, being uncommon amongst Westerners, but
reaching as high as 20% in people from Asia and Africa. Thus, the
disease is very common amongst Chinese. With immigration of
Chinese into Western countries, hepatitis B is now becoming
established in countries where it was previously uncommon.
Approximately 10 percent of patients contract hepatitis B as an
adult and that is usually the case amongst Westerners. In the
Chinese population, hepatitis B is usually transmitted from
infected mother to the newborn infant. Because of the immature
immune system in these infants, they cannot clear the virus from
their bodies. They therefore remain infected for life. Such
infected individuals act as potential reservoirs of infection and
can transmit the disease through kissing, sharing of toothbrushes,
razors and sexual contact. Hepatitis B can also be transmitted
through blood transfusion, although the incidence of this
happening is very low now since routine screening of blood
donations. Intravenous drug users who share needles with others
and health-care workers who handle blood samples are also at high
risk of contracting hepatitis B.
Currently, it is estimated that approximately 20 percent of the
are infected with hepatitis B. Many infected
individuals cannot remember being ill with hepatitis. The virus
may remain dormant and these people are usually a symptomatic and
therefore referred to as healthy carriers. However, a significant
portion of patience may have ongoing liver damage despite
remaining asymptomatic. Occasionally their liver inflammation can
be so severe that the patient feels ill with nausea, loss of
appetite and becomes jaundiced. Repeat episodes of liver damage
will lead to scarring of the liver called cirrhosis which will
lead to many complications including the development of liver
Because many patients with liver inflammation remain
asymptomatic, they may progress to liver cirrhosis or even liver
cancer silently. Therefore it is important for the Chinese
population to be screened for hepatitis B. Once hepatitis B is
diagnosed, the treating physician will determine from various
investigations and abdominal ultrasound the extent of liver
inflammation. If the patient has normal liver function tests as
well as a normal and abdominal ultrasound, he needs to be followed
up regularly by his family physician since it is totally
the virus will become active. Blood tests are
recommended every six months and abdominal ultrasound every year.
The patient should also be screened for the presence of liver
cancer, especially in males older than 40 years of age. Should
liver inflammation be detected, patient should be referred for a
specialist opinion. The specialist will undertake further
investigations which may include a liver biopsy to determine the
extent of inflammation and cirrhosis. Treatment is now available
for hepatitis B and it should be offered to patients who have
persistence inflammation for more than six months. Once cirrhosis
is established treatment is less effective. Therefore, patients
should be screened and treatment offered before a there is any
significant liver damage.
Approved treatment for hepatitis B is Interferon given over a
period of 16 weeks during which time the patient is closely
monitored. Treatment with Interferon is associated with some side
effects which tend to settle down after the initial few weeks. The
dose of Interferon may be reduced should the side effects become
intolerable. Approximately 50 percent of patients treated with
Interferon will a favorable response with the virus being
converted from the active to be inactive form. Treatments are now
being developed for those patients who were unsuitable for
Interferon treatments or have failed Interferon treatment. These
are still currently being used in investigational studies.
Once an index case of viral hepatitis B is identified, the
entire family should be screened for hepatitis B. Some members of
the family may have been infected but cleared the virus and
therefore have become immune. Other members may be chronic
carriers, while others may still be unexposed to the virus. those
individuals who have cleared the virus do not require further
medical attention. Those individuals not yet exposed to the virus
should be vaccinated against hepatitis B while chronic carriers
need to be cared in the same way as the index case. Vaccination
against hepatitis B is very effective and consists of the course
of three injections. Vaccination can be arranged with the family
physician. Once the course
is completed, the individual is
protected for life. Currently various provincial governments have
agreed to fund vaccination for children in grades 7. It is
recommended that all children in communities with high carrier
rates, such the Chinese community, should be vaccinated from birth
or as soon as possible once they have been screened and found to
be unexposed. Is only with a mass vaccination program that we can
hope to eradicate hepatitis B in the next generation.
Viral Hepatitis C Infection
Hepatitis C virus is another virus which infects the liver. It
is made up of a family of similar viruses and they are
structurally different from the hepatitis B virus. The
distribution of hepatitis C infection differs from that of
hepatitis B in that it is particularly prevalent in certain
countries such as Japan, Korea, Vietnam and China. It is mainly
transmitted through contact with infected blood. Therefore,
patients who required transfusion of blood and blood products are
risk, together with patients who have had injections with shared
needles. Unlike hepatitis B, infection with hepatitis C usually
occurs in adulthood. Once infected, the majority patients will not
be able to get rid of the virus, but rather will have ongoing
inflammation ultimately leading to cirrhosis. Hepatitis C is a
very slow growing virus and this process of smoldering
inflammation may take 20 years before symptoms develop. Certain
subgroups of patients tend to have a more rapid progression of the
disease leading to cirrhosis in a few years and these are usually
patients who contracted the disease at an older age, patients who
abuse , alcohol and patients who also have hepatitis B infection.
Once symptoms develop, the liver disease is usually quite advanced
and complications of cirrhosis are usually present. Therefore, it
is important to screen patients from high prevalence countries for
hepatitis C, even at the asymptomatic stage, so that treatments
can be offered before the development of cirrhosis.
Once the patient is diagnosed to have hepatitis C infection,
investigations including blood test and ultrasound and the liver
biopsy will be performed to determine the severity of the
inflammation and to assess for the presence of cirrhosis.
Screening for liver cancer is also performed since patients
infected with hepatitis C also are at higher risk for the
development of liver cancer.
The currently recommended treatment for hepatitis C infection
is Interferon. Like hepatitis, the treatment is more effective
before the development of cirrhosis. Our present experience
recommends treatment for a period of 12 months. Side effects tend
to be less severe since these patients require a lower daily dose
than those being treated for hepatitis B. The response rate to
Interferon as approximately 30% after one year of treatment.
Recently, a new anti-viral agent in the form of an oral
medication, has been used in combination with Interferon with
improved response rates. Patients being treated with Interferon
for hepatitis C with or without the oral agent, need to be
monitored regularly. Successful treatment will suppress liver
inflammation and convert the patient from an active phase to a
dormant phase of the disease. This will slow down progression to
cirrhosis and also reduce the risk of the development of liver
Currently, there is no available vaccination against hepatitis
C infection. The only effective prevention is to avoid contact
with infected blood. Current practices with blood transfusion
should make the risk of contracting viral hepatitis C minimal.
Patients who are infected should not share their razors
toothbrushes, or shavers. Sharing needles should also be avoided.
Patients with hepatitis C should not drink alcohol, because the
combination of alcohol and hepatitis C will accelerate the
progression to cirrhosis and even increase the risk of liver
cancer. Currently, Hepatitis C infection is the biggest epidemic
worldwide. Active screening and treatment of suitable cases is the
only possible means of controlling this problem.
of the HBsAg-positive patient
Any patient with clinical or laboratory evidence for either
acute or chronic liver disease should be considered as possibly
infected with HBV. Individuals engaged in high-risk activities
such as intravenous drug use or high-risk sexual activity are at
risk, as well as individuals exposed to blood by reason of their
occupation.In addition being a member of a population with a high
endemic rate of HBV is a risk factor for infection.
The diagnosis of HBV infection is based on the detection of HBsAg
All HBsAg-positive individuals require further detailed
assessment. The objectives are to characterize the nature of
the infection and the extent and severity of any underlying liver
disease. Other objectives include identifying patients who may
benefit from anti-viral treatment, early diagnosis and management
of cirrhosis and its complications, timely detection of HBV-associated
hepatocellular carcinoma, and immunization of contacts at risk.
Chronic hepatitis B Initial
The laboratory tests needed in the initial assessment in all cases
of chronic HBV infection are listed in table 2.
Table 2.Initial investigation of the hepatitis B carrier
Liver function tests
Other important tests
BUN or creatinine
CBC and differential
Measurement of the aminotransferases provide a measure of ongoing
inflammation, whereas the bilirubin, albumin and INR estimate
liver function. Anemia, leukopenia or thrombocytopenia may
indicate cirrhosis with portal hypertension. A positive
HBeAg is associated with the continued presence of actively
replicating HBV in the liver and detectable HBV DNA in the blood.
Such patients are at risk for ongoing liver injury. Their blood
and body fluids are highly infectious. Anti-HBe-positive patients
may have much lower viral loads, which may be undetectable in
blood by standard assays. These patients usually have little
ongoing liver damage. Anti-HBe-positive patients may be infected
with the so-called pre-core mutant, which does not produce
HBeAg. These patients may have detectable HBV DNA and may develop
progressive liver disease leading to cirrhosis, and therefore
merit life-long observation.
In selected cases additional tests are needed. Anti-HCV should be
requested in patients at high risk (IVDU, high risk sexual
exposures, origin in countries of high HCV prevalence).For those
at risk for hepatocellular carcinoma (long term and childhood
infections, positive family history), and those in whom cirrhosis
is suspected an ultrasound is strongly advised.
B - Clinical Features
60-90 days Range 45-180 days
yrs, <10% ณ5 yrs, 30%-50%
yrs, 30%-90% ณ5 yrs, 2%-10%
mortality from chronic liver disease:
T he incubation period for hepatitis B ranges from 45-180 days
(mode, 60-90 days), and the onset of acute disease is generally
insidious. Clinical illness associated with acute infection is
age-dependent with jaundice occurring in <10% of children less
than 5 years of age and in 30%-50% of older children and adults. The
case-fatality rate for reported acute cases in the United States is
approximately 0.5%-1%. Most acute HBV infections in adults result in
complete recovery with clearance of HBsAg from the blood and the
production of anti-HBs designating immunity from future infection.
However, approximately 30%-90% of young children and 2%-10% of
adults who are infected with HBV develop chronic infection, and most
of the serious sequelae associated with HBV occur in these persons.
Persons with chronic HBV infection are often asymptomatic, but these
persons are at high risk for developing chronic hepatitis, and
approximately 15%-25% may die prematurely from either cirrhosis or
HBV DNA can be detected in serum by several commercially available
methods (see later).Table 3 lists the current tests, their limits
Table 3.Manufacturers reported dynamic ranges for HBV DNA
Abbott Solution Hybridization Assay
1.6 to~800 pg/ml
Digene 1st Generation Hybrid Capture Assay
5-2000 pg/ml (1.4x106 5.6x108 copies/ml)
Digene 2nd Generation Hybrid Capture Assay
1.4x105 1.7x109 copies/ml
4.7x103 5.6x107 copies/ml
Chiron Quantiplex™ bDNA Assay
0.7 5000 Meq/ml (7x105 5x109
Roche AMPLICOR™ HBV Monitor™ PCR Assay
1000 1x107 copies/ml
is poor inter-assay standardization so that quantification of HBV
DNA when tested on different assays can vary by approximately 10
fold or more when testing the same specimen. There is also
considerable intra-assay variation so that repeat testing of the
same sample will result in a significant difference in results
(coefficient of variation for bDNA assay is 10-20%, and for PCR
assays is 20-40%).It is therefore important for the clinician to
understand the type of assay methodology used, and its limitations,
and that a consistent methodology be used for all assays.
DNA testing should be limited to those patients being considered for
treatment and to evaluate response to treatment. It is not indicated
routinely in the evaluation of all HBsAg-positive patients.HBV DNA
testing should be readily available to qualified practitioners
regularly involved in the treatment of HBV.
Biochemical or serological tests, including HBV DNA, cannot
predict histopathology with adequate precision. Therefore liver
biopsy may be required to determine the severity of permanent
liver injury (fibrosis or cirrhosis). The biopsy appearances may
help in choosing appropriate therapy.
The detection of IgM anti-HBc in the serum is not a reliable
surrogate for HBV DNA testing. Its use is not recommended for this
purpose. Positive immunostaining of hepatocyte nuclei and
cytoplasm for HBcAg reliably predicts the presence of HBV DNA in
Specific Immunotherapy for the Control of Hepatitis
B Virus Multiplication
Professor Cell Biology/Hepatology
Key Learning Objectives
At the end of the session, the participants will be
define the concept of "specific immunotherapy"
clearly delineate its potential side effects
update the literature on data obtained with current vaccines
define new strategies and, in particular, the concept of
summarize the data available with DNA vaccines for HBV
evaluate the potentials and drawbacks of this approach
Despite significant improvements, the treatment of
chronic hepatitis due to HBV infection remains insufficient. Several
lines of evidences suggest that tolerance to HBV might be, at least in
part, abrogated by a specific immunotherapy. Thus, B lymphocytes of
HBV chronic carriers have retained their capacity to synthetize anti-HBsAg
antibodies. In addition, injection of HBsAg protein to HBV
expressing transgenic mice induces a significant reduction in HBV
viremia and HBsAg titers, together with anti-HBs detection.
We have previously suggested in a pilot study that
vaccination against HBV using a regular, PreS2/S or S-based vaccine,
might abolish or significantly lower HBV multiplication in around 30%
of patients with HBV-related chronic hepatitis. We will present recent
results from a randomized prospective study which confirms the
potential of this approach.
We have indeed comparatively evaluated the efficacy
of six injections of the Genevac B (PreS2/S), the Recombivac (S). We
were able to demonstrate that three injections of either PreS2/S or
S-based vaccines were sufficient to abolish serum HBV DNA detection in
13/84 patients, compared to only 1/37 unvaccinated controls (p=0.04).
In addition, anti-HBe seroconversion was only observed after 6-month
follow-up in the vaccinated patients.
Finally we were able to demonstrate induction of a
PreS/S specific T cell proliferation upon vaccination. Thus,
collectively, these data pave the way for the use of immunotherapy for
the treatment of HBV infection.
Still, the currently available recombinant vaccines
show a too limited efficacy. These results therefore, stimulate the
development of new approaches to achieve a more efficient and durable
Beside the use of PreS1/S2/S-based vaccines which
are now evaluated, DNA vaccination shows great promise and is
currently being evaluated for HIV. DNA vaccination against HBV is
based on the direct in vivo expression of HBsAg from a recombinant
plasmid injected intramuscularly. Several studies, performed in mice
and primates have demonstrated the capacity of such constructs to
induce both humoral and cellular immune (in particular Th1) responses
to the viral antigen. This efficacy is due to the neosynthesis of
viral peptides from the injected plasmids. The production of anti-HBs
has been shown to be stable after an 18 month follow-up and this
humoral immune response does mimic that observed during natural
infection. On the same line, injection of a 10 microgram dose of HBsAg
encoding plasmid to BALB/c mice induces, for at least 12 weeks, a
cytotoxic T cell response. Studies in ducks and woodchucks infected
with the Hepadnaviruses DHBV and WHV, respectively, have confirmed the
potential of this approach by showing protection against viral
challenge and induction of specific neutralizing antibodies.
Experiments performed in macaques have confirmed the possibility to
induce a humoral and immune response to HBV and thus prompt clinical
evaluation of this strategy.
There is so far no evidence for side-effects
specific to this therapeutic approach and clinical studies are now
initiated to thoroughly evaluate the actual clinical relevance of this
elegant treatment option in humans.
- Davis HL, McCluskie MJ, Gerin JL, Purcell RH. DNA vaccine for
hepatitis B: evidence for immno-genicity in chimpanzees and
comparison with other vaccines. Proc Natl Acad Sci USA
- Davis HL, Michel ML, Mancini M, Schleef M, Whalen RG. Direct
gene transfer in skeletal muscle: plasmid DNA-based immunization
against the hepatitis B virus surface antigen. Vaccine
- Geissler M, Tokushige K, Wakita T, Zurawski VR Jr, Wands JR.
Differential cellular and humoral immune responses to HCV core and
HBV envelope proteins after genetic immunizations using chimeric
constructs. Vaccine 1998;16:857-67.
- Le Borgne S. Mancini M, Le Grand R, Schleef M, Dormont D,
Tiollais P, et al. In vivo induction of specific cytotoxic T
lymphocytes in mice and rhesus macaques immunized with DNA vector
encoding an HIV epitope fused with hepatitis B surface antigen.
- Mancini M, Hadchouel M, Davis HL, Whalen RG, Tiollias P, Michel
ML. DNA-mediated immunization in a transgenic mouse model of the
hepatitis B surface antigen chronic carrier state. Proc Natl Acad
Sci USA 1996;93:12496-501.
Asked and Question about Hepatitis B Virus
How do you get hepatitis B?
You get hepatitis B by direct
contact with the blood or body fluids of an infected person; for
example, you can become infected by having sex or sharing needles with
an infected person. A baby can get hepatitis B from an infected mother
Hepatitis B is not spread through
food or water or by casual contact.
What does the term "hepatitis B carrier" mean?
Hepatitis B carriers are people
who are infected with HBV and never recover fully from the infection;
they carry the virus and can infect others for the rest of their lives.
In the United States, about one million people carry HBV.
How do you know if you have hepatitis B?
You may have hepatitis B (and be
spreading the disease) and not know it; sometimes a person with HBV
infection has no symptoms at all.
If you have symptoms
- your eyes or skin may turn
- you may lose your appetite
- you may have nausea. vomiting,
fever, stomach or joint pain
- you may feel extremely tired
and not be able to work for weeks or months
Is there a cure for hepatitis B?
There are medications available
to treat long-lasting HBV-infection (carrier). These work for some
people, but there is no cure for hepatitis B when you first get it. That
is why prevention is so important. Hepatitis B vaccine is the best
protection against HBV. Three doses are commonly needed for complete
If vaccine was never given, children 0-18 years of age should
get hepatitis B vaccine.
If you are pregnant, should you worry about hepatitis B?
If you have HBV in your blood,
you can give hepatitis B to your baby. Babies who get HBV at birth may
have the virus for the rest of their lives, can spread the disease, and
can get cirrhosis of the liver or liver cancer.
All pregnant women should be tested for HBV early in their pregnancy. If
the blood test is positive, the baby should receive vaccine along with
another shot, hepatitis B immune globulin (called H-BIG), at birth. The
second dose of vaccine should be given at 1-2 months of age and the
third dose at 6 months of age.
Who should get vaccinated?
All babies, at birth
- All children 0-18 years of age
who have not been vaccinated
- Persons of any age whose
behavior puts them at high risk for HBV infection
- Persons whose jobs expose them
to human blood
Fact Sheet: Vaccine
- Hepatitis B is a serious
disease, responsible for an estimated 4000 to 5000 deaths each year
in the United States due to cirrhosis and liver cancer.
- Hepatitis B vaccine prevents
hepatitis B disease and its serious consequences. Therefore, this is
the first anti-cancer vaccine.
- Use of hepatitis B vaccine and
other vaccines is strongly endorsed by the medical, scientific and
public health communities as a safe and effective way to prevent
disease and death.
- Hepatitis B vaccines have been
shown to be very safe when given to infants, children and adults.
- There is no confirmed evidence
that indicates that hepatitis B vaccine can cause chronic illnesses.
- Case reports of unusual
illnesses following vaccines are most often related to other causes
and not related to a vaccine. Whenever large number of vaccines are
given, some adverse events will occur coincidentally after
vaccination and be falsely attributed to the vaccine.
- To assure a high standard of
safety with vaccines, several federal agencies continually assess
and research possible or potential health effects that could be
associated with vaccines.
- Anyone believing they have had
a possible reaction or adverse health effect from a vaccine should
report it to their health care provider. The Vaccine Adverse Events
Reporting System (1-800-822-7967) receives reports from health care
providers and others about vaccine side effect.
INTERFERON TREATMENT FOR HEPATITIS B AND C
What is interferon?
- Interferon is produced by the body's cells in response to viral hepatitis and other infections. There are three types--alpha, beta and gamma. All are proteins. Commercial alpha interferon mixtures consist of the types of interferon produced by the body. Interferon alpha-2b is the only commercial form approved by the U.S. Food and Drug Administration for the treatment of hepatitis B and C. However, other forms of alpha interferon (interferon alpha-2a, lymphoblastoid or "natural" interferon and "consensus" interferon) are being evaluated. Interferons stimulate the body's immune system to fight viral infections and affect the ability of viruses to divide in liver cells. Patients with chronic hepatitis B or C infections also appear to be unable to produce normal amounts of interferon.
Which patients with hepatitis B should take interferon?
- Less than 50% of patients with chronic hepatitis B infection are eligible for interferon therapy. Patients should have infection documented for at least six months, elevated liver enzymes (AST or SGOT, and ALT or SGPT tests) and an actively dividing virus in their blood (hepatitis "e" antigen (HBeAg) and/or hepatitis B virus DNA (HBV DNA) positive tests). Patients with normal liver enzymes are less likely to respond to therapy. Patients with low hepatitis B virus DNA levels and elevated liver enzymes are more likely to benefit than those with high HBV DNA levels. A biopsy, where a needle is inserted into the liver to obtain a small sample of tissue, is helpful to determine liver damage prior to treatment. Patients with acute infection, cirrhosis or other major medical problems should not be treated.
When is it indicated for hepatitis C?
- Patients with elevated liver enzymes for six or more months and who have a detectable antibody (ELISA test) to hepatitis C (anti-HCV) are eligible for therapy. Patients who have a risk factor for hepatitis C (blood transfusion, needle-stick exposure or illegal intravenous drug use) need not have the hepatitis C result confirmed by additional testing. However, patients without such a risk factor should have a second test (RIBA test). Liver biopsy is helpful in the diagnosis of viral hepatitis, assessing liver damage prior to treatment, and at the end of therapy to evaluate the response. Patients with acute infection, complications from cirrhosis, other major medical problems and autoimmune liver disease should not be treated with interferon.
What are the doses used?
- The standard approved dose for hepatitis C is three million units, three times weekly for 24 weeks. Approved treatment for hepatitis B is five million units daily for 16 weeks. Treatment may be modified for significant side effects. However, lower doses may result in lower rates of response. Higher doses or longer therapy are being tested.
What are the side effects of treatment?
- The most common serious side effect is depression, particularly in patients with a prior history. Most patients will have muscle aches, fatigue and low grade fevers. These can be minimized by taking low doses of acetaminophen (e.g. Tylenol) at night. Nausea and diarrhea are common as is irritation of the skin at the injection site. Patients may experience significant weight loss, and if this occurs the dose should be adjusted. Patients often complain of irritability and headaches. A small number of patients may develop thyroid disease. Normal thyroid function should be documented prior to treatment. Hair loss is not uncommon, but usually reversible. Few side effects are severe or persist after treatment.
When is treatment not indicated?
- Patients with chronic hepatitis B or C, with fluid in the abdomen (ascites), bleeding from dilated veins in the esophagus (variceal bleeding), or mental confusion (encephalopathy) should be treated only in a clinical trial. Others not suitable for treatment are those with symptomatic heart, lung or kidney disease, with human immunodeficiency virus (HIV) infection or organ transplant recipients on prednisone, cyclosporine and FK-506 and patients on antidepressants or with a history of suicide attempts. Interferon should not be given to women considering pregnancy, nor to the intended father. Patients with active substance abuse (alcohol or illegal drugs) should not be offered this therapy.
What can be expected from treatment?
- Approximately 40%-50% of patients with chronic hepatitis C receiving full dose therapy will have a normalization of their liver enzymes, usually by the third month. With normal liver tests, the virus may become undetectable in blood. If no response is seen by three months, most researchers advocate stopping therapy. A few patients who respond to therapy may see their liver enzymes rise towards the end of treatment. The reason for this is unknown. When interferon is stopped after six months, more than half of the patients with hepatitis C who have responded will experience a rise in their liver tests. Patients will usually respond again if given further therapy. Therefore, 10%-15% will have a long lasting positive response. Longer treatments will likely result in longer positive responses. However, there is no evidence that this affects the relapse rate when treatment is stopped. Few patients will eradicate the virus.
A positive response to treatment for hepatitis B occurs in about 35% of patients. This is usually associated with a normalization of liver enzymes, and a loss of three "markers" for an active infection. These markers are hepatitis "e" antigen (HBeAg), hepatitis B DNA (indicating that the virus is reproducing) and hepatitis B surface antigen (HBsAg). An estimated 6% to 20% of patients lose these markers after therapy is stopped. A positive response to therapy is preceded by a rise in liver enzymes. Why this happens is not understood. Complete elimination of the virus is seldom achieved.
What happens if interferon is not given?
- The long term prognosis of hepatitis C is poorly understood. However, hepatitis C is generally a slowly progressive disease, with evolution over years if not decades. There is no proof that six months of treatment with interferon alters this. The changes vary from mild chronic hepatitis (least amount of liver damage) to moderate or severely active chronic hepatitis, with or without fibrosis or cirrhosis (most amount of liver scar damage). It is not known who will develop complications of chronic liver disease and liver failure.
In contrast, hepatitis B tends to progress more rapidly over years, although occasionally over decades. Not all patients with either hepatitis B or C will develop complications of liver disease. However, for hepatitis B, interferon should be considered strongly in eligible patients. In addition, patients with chronic hepatitis B are less than ideal candidates for transplantation because of damage to the new liver. Patients transplanted for hepatitis B or C will usually see a recurrence of the viruses.
What new drugs are available?
- Much is unknown about treatment with interferon. Therefore, when possible, patients should consider participating in clinical trials. Different kinds of interferons and other new drugs, by themselves or in combination with other drugs, are being evaluated for both hepatitis B and C.