Hepatitis B vaccine and multiple sclerosis
Hepatitis B is a virus that causes inflammation of the
liver and can lead to liver scarring and cancer. A vaccine to prevent
hepatitis B has been very safe and effective. In the last decade there
have been concerns that hepatitis B vaccine may be associated with development
of the neurologic disorder multiple sclerosis. However,
numerous scientific studies and expert panel reviews do not suggest a
link between the hepatitis B vaccine and multiple sclerosis.
This fact sheet answers the following commonly asked questions. More general
information on the hepatitis B vaccine is also available by following
the links in Further Reading.
• What is hepatitis B?
• What is multiple sclerosis (MS)?
• Does the hepatitis B vaccine cause multiple sclerosis?
• Are there studies that suggest a link between hepatitis
B vaccine and MS?
• Can hepatitis B vaccine make MS worse?
• What have expert reviews concluded?
• Further reading
Hepatitis B is a viral infection that causes acute inflammation of the liver (hepatitis). It is transmitted from person to person by contact with blood and body fluids in activities such as sexual intercourse, intravenous drug use and blood transfusion. It can also be passed from an infected mother to her baby around the time of birth. There is evidence that children may transmit it to each other through contact that occurs while playing.
Some people with hepatitis B will develop chronic infection and are known as "carriers". Hepatitis B carriers may not know they are infected and may have no symptoms. However, chronic hepatitis B infection can lead to cirrhosis (scarring) of the liver or cancer of the liver. The chance of becoming a carrier is greatest when the infection is acquired at an early age. For example, an infected newborn baby has a 90% risk of becoming a carrier. This is why universal vaccination of all infants is recommended in Australia and many other countries. Each year approximately 600,000 hepatitis B related deaths occur worldwide and there are 350 million chronic carriers of the virus.
The vaccine against hepatitis B infection is made by recombinant DNA
technology, which produces inactive (non-infectious) subunits of the virus.
When injected into non-immune people, the vaccine gives a high level of
protection against hepatitis B infection. The World Health Organisation
has set a goal for all countries to have hepatitis B vaccination as part
of their universal childhood vaccination programs.
What is multiple sclerosis (MS)?
Multiple sclerosis (MS) is a chronic illness resulting from inflammation and scarring of the myelin sheaths in the brain and spinal cord. Myelin forms a protective covering over nerves and helps conduction of electrical signals along nerves. MS is also known as a “demyelinating disease”. People with MS can experience varying degrees of incapacity, such as loss of vision and impairment of physical activity, depending on the location and severity of the scarring. There is often a fluctuation in the disease symptoms over time, known as exacerbations and remissions. In Australia there are between 12,000 and 15,000 people with MS, and worldwide there are an estimated 2.5 million people with MS.
The cause of MS is unknown. It is suggested that in patients with a genetic predisposition the disease may be triggered by environmental factors. Multiple sclerosis typically begins between the ages of 20 and 40, and is 2-3 times more common in women than in men. The incidence of MS varies geographically, with higher rates in temperate climates. Even within Australia there is a lower incidence of MS in Queensland compared to the cooler Southeastern states. Non-specific upper-respiratory tract infections have been implicated in triggering or exacerbating MS, usually within a short time period after the infection. Triggers such as viruses are thought to cause viral mimicry of myelin antigens, and to activate immune responses that act against myelin proteins. However, the hepatitis B virus has not been implicated as a trigger.
Does hepatitis B vaccine cause multiple sclerosis?
No, the weight of all the currently available scientific evidence shows
no association between hepatitis B vaccine and multiple sclerosis. Concern
about hepatitis B vaccination arose from France in the mid 1990’s.
Following a mass hepatitis B vaccination program in France there were
reports of MS developing in some patients a few weeks after receiving
the vaccine. In 1998 the French government stopped the school-based hepatitis
B component of the vaccination program while they investigated a possible
relationship between hepatitis B vaccine and demyelinating disease. When
studies of the French vaccine recipients were completed they showed that
there was not a significant increase in the number of vaccinated people
who developed MS as compared with those who had never received hepatitis
B vaccine. Since that time there have been more than 7 published studies
that have consistently shown no association between receipt of hepatitis
B vaccine and MS. Some of the other findings that support this include:
• A study In British Columbia, Canada that investigated multiple
sclerosis in 578,308 adolescents over an 8 year period before and after
a hepatitis B vaccination program was begun. The results showed no evidence
of a link between hepatitis B vaccination and multiple sclerosis or other
demyelinating disease.
• A study in 2001 of 192 women with MS and 645 control patients
who did not have MS that showed no increased risk of MS in those who received
hepatitis B vaccine.
• Another study in 2001 looked at hepatitis B, tetanus, and influenza vaccines in patients with MS, and showed no evidence of these vaccines being associated with MS relapses (worsening of MS symptoms).
• A study in the United States of over 1400 participants did not show any association between hepatitis B vaccination and MS or other types of demyelinating disease.
• Mass immunisation programs with hepatitis B vaccine in New Zealand,
Taiwan and Alaska have not resulted in any serious adverse events or illnesses
suggestive of MS.
• Extensive pre-licensure clinical trials of hepatitis B vaccine
did not document MS as a side effect.
Are there studies that suggest a link between Hepatitis B vaccine and MS?
Despite many studies and expert reviews over the last decade that have
found no association between hepatitis B vaccine and MS, the question
of a link has been raised again by a study published in 2004 by Hernán
and colleagues.
This study was performed by looking back at the medical records of adult
patients in the UK who were immunised against hepatitis B by GPs. The
authors based their results on a small number of MS patients (11) who
had previously received the hepatitis vaccine, and suggest that there
may be an increased risk of developing MS in the 2nd and 3rd years after
receiving the vaccine. However there are numerous misgivings that are
important to understand regarding this study.
The following points are important to put the study in context:
1) The study relied on accurate recording of all immunisation
records and disease symptoms by GPs. However, given the few patients involved,
even a minimal difference in the way the information was recorded could
alter the results
2) In the UK hepatitis B vaccine is only targeted toward
adults at high risk of getting hepatitis B. Therefore the persons who
received the vaccine in this study are not representative of the general
population and this may have skewed the results. Also, health workers
in the study may have received their hepatitis B immunisation in the workplace,
rendering information from the GPs incomplete and possibly affecting the
study results.
3) Although there were 713 cases of MS in the database,
only 11 were selected in the final analysis - this may have biased the
results
4) Information on the number hepatitis B vaccine doses
given, and the time over which they were given is missing and means that
interpretations regarding the effect of the timing and dosing of vaccine
cannot be accurately made, and
5) An association between receiving hepatitis B vaccine
more than 1 year prior to the onset of MS seems unlikely given that viruses
that may trigger the onset of MS are thought to have an affect within
weeks.
An editorial accompanying this study stated that the “data presented
do not provide proof of association sufficient to implement policy changes.
The indisputable benefit that the HBV provides against infection must
be weighed against any uncommon risks that remain disputed.” The
World Health Organization (WHO) has made a statement that "the findings
do not provide convincing support for the hypothesis that immunisation
with recombinant hepatitis B vaccine is associated with an increased risk
of multiple sclerosis." Because of the methodological problems of
the Hernán study, and the fact that it is in contrast to many other
studies, experts consider that the findings do not provide convincing
evidence of an association between hepatitis B vaccine and MS.
Can hepatitis B vaccine make MS worse?
Worsening of MS can occur after non-specific viral illnesses. This is
thought to be due to activation of the immune system caused by the infection.
Although there have also been case reports in MS patients of worsening
of their symptoms after vaccination, a well conducted study of influenza
vaccine in people with MS did not show any worsening of MS after receiving
vaccination. In addition, a study conducted in Europe involving 643 individuals
with MS has shown no evidence of an association between recent receipt
of hepatitis B vaccine (or tetanus or influenza vaccination) and MS relapses.
The National Multiple Sclerosis Society provides information on the importance
of vaccinating people with MS with all appropriate vaccines, including
the hepatitis b vaccine: http://www.nationalmssociety.org/Brochures-PreventiveCare2.asp.
What have expert reviews concluded?
The studies on hepatitis B vaccine and MS have been reviewed by the World Health Organisation Global Advisory Committee on Vaccine Safety. They state that “multiple studies and review panels have concluded that there is no link between MS and hepatitis B vaccination”. The WHO also affirm that the recent study by Hernán and colleagues does not provide sufficient evidence to link hepatitis B vaccination to MS, and does not justify discontinuation or modification of programs with hepatitis B vaccine (see link HERE.)
In addition, a review by the Institute of Medicine Immunization Safety
Review Committee in 2003 found that there was no link found between hepatitis
B vaccine and certain neurological disorders such as MS. A systematic
review from the Cochrane Vaccines Field in 2003, also found no evidence
of an association between hepatitis B vaccine and MS. Recent statements
by the US Centers for Disease Control, and the National Network for Immunization
Information support this position.
Further reading
More general information about hepatitis B vaccine is available from “Understanding
Childhood Immunisation” page 28 at http://immunise.health.gov.au/uci_2.pdf
Additional Web-based information
1. US Centers for Disease Control and Prevention. Multiple sclerosis and
the hepatitis B vaccine: http://www.cdc.gov/nip/vacsafe/concerns/ms/default.htm
(accessed Dec 2004).
2. US Centers for Disease Control and Prevention. “Recombinant hepatitis
B vaccine and the risk or multiple sclerosis. Key messages” Sept
14, 2004 http://www.cdc.gov/ncidod/diseases/hepatitis/b/hbv_ms.pdf
(accessed Dec 2004).
3. Institute of Medicine Press Report: No Link Found Between Hepatitis
B Vaccine and Certain Neurological Disorders (accessed Dec 2004).
http://www4.nationalacademies.org/news.nsf/isbn/0309084695?OpenDocument
4. US Centers for Disease Control and Prevention. Hepatitis B Vaccine
and Demyelinating Neurological Disorders. http://www.cdc.gov/nip/news/iom-hepb-5-2002/iom.htm
(accessed Dec 2004)
5. World Health Organisation. Hepatitis B vaccination and multiple sclerosis
(MS) http://www.who.int/vaccine_safety/topics/hepatitisb/multiple_sclerosis/en/
(accessed Dec 2004)
6. World Health Organisation.The Global Advisory Committee on Vaccine
Safety rejects association between Hepatitis B vaccination and multiple
sclerosis (MS) http://www.who.int/vaccine_safety/topics/hepatitisb/ms/en/
(accessed Dec 2004)
7. National Network for Immunization Information. Immunization Issues:
Hepatitis B Vaccine and Multiple Sclerosis. http://www.immunizationinfo.org/immunization_issues_detail.cfv?id=74
(accessed Dec 2004)
Scientific papers
1. Sadovnick AD, Scheifele DW. School-based hepatitis B vaccination programme
and adolescent multiple sclerosis. Lancet 2000;355:549-50.
2. Hall A, Kane M, Roure C, Meheus A. Multiple sclerosis and hepatitis
B vaccine? Vaccine 1999;17:2473-5.
3. Halsey NA, Duclos P, Van Damme P, Margolis H. Hepatitis B vaccine and
central nervous system demyelinating diseases [review]. Viral Hepatitis
Prevention Board. Pediatric Infectious Disease Journal 1999;18:23-4.
4. MacIntyre CR. Hepatitis B vaccine: risks and benefits of universal
neonatal vaccination. J Paediatr Child Health 2001;37:215-217.
5. Ascherio A, Zhang SM, Hernan MA, et al. Hepatitis B vaccination and
the risk of multiple sclerosis. N Engl J Med 2001;344:327-332.
6. Confavreux C, Suissa S, Saddier P, et al. Vaccinations and the risk
of relapse in multiple sclerosis. Vaccines in Multiple sclerosis Study
Group. N Eng J Med 2001;344:319-326.
7. Verstraeten T, DeStefano F, Jackson L, et al. Risk of demyelinating
disease after hepatitis B vaccination - West Coast, United States, 1995-1999.
Paper presented at the 50th Annual Epidemic Intelligence Service Conference
, 2001, Atlanta GA.
8. Rutschmann OT, McCrory DC, Matchar DB; Immunization Panel of Multiple
sclerosis Council for Clinical Practice Guidelines. Immunization and MS:
a summary of published evidence and recommendations. Neurology
2002;59:1837-1843.
9. DeStefano F, Verstraeten T, Jackson LA. Vaccinations and risk of central
nervous system demyelinating diseases in adults. Archives of Neurology
2003;60:504-509.
10. Hernán M, Jick SS, Olek MJ, Jick H. Recombinant hepatitis B
vaccine and the risk of multiple sclerosis. A prospective study. Neurology.
2004; 63:838-842.
Naismith RT, Cross AH. Does the hepatitis B vaccine cause multiple sclerosis?
Editorial. Neurology. 2004; 63: 772-773.
11. Touze E, Gout O, Verdier-Taillefer MH, et al. The first episoce of
central nervous system demyelinization and hepatitis B vaccination. Rev
Neurol 2000; 156:242-6.
12. Zipp F, Weil JG, Einhaupl KM. No increase in demyelinating diseases
after hepatitis B vaccination. Nat Med 1999;5:964-5.
13. Demicheli V, Rivetti A, Di Pietrantonj C, Clements CJ, Jefferson T.J
Hepatitis B vaccination and multiple sclerosis: evidence from a systematic
review. Viral Hepat. 2003 Sep;10(5):343-4.
14. Sturkenboom MCJM, Abenhaim L, Wolfson C, Roulet E, Heinzelf O, Gout
O. Vaccinations, demyelination, and multiple sclerosis study (VDAMS).
Pharmacoepidemiol Drug Safety 1999;8:S170-1.
15. Fourrier A, Touze E, Alperovitch A, Begaud B. Association between
hepatitis B vaccine and multiple sclerosis: a case-control study. Pharmacoepidemiol
Drug Safety 1999;8:S140-1.
Updated 1 February 2005