Hepatitis B is a common form of hepatitis which can be transmitted parenterally, through sexual contact and from mother to infant. It is an important cause of acute and chronic infection of the liver. More than a third of the world’s population is infected with the hepatitis B virus (HBV), and WHO estimates that it results in 1 – 2 million deaths annually.
The virus persists in 5-10% of immunocompetent adults and in as many as 90% of infants infected perinatally. Persistent carriage of HBV is defined by the presence of hepatitis B surface antigen (HBsAg) in the serum for more than 6 months. It occurs in more than 350 million individuals worldwide. Long-term continuing virus replication may lead to chronic liver disease, cirrhosis and hepatocellular carcinoma. Primary liver cancer is one of the ten most common cancers worldwide and about 80% of these are ascribed to persistent infection with HBV.
Malaysia was an intermediate endemicity country with HBsAg prevalence of 5 – 7% before nationwide HBV vaccination for neonates was introduced in 1989 as part of the Expanded Programme for Immunisation. The programme was successful as the prevalence of chronic HBV infection among those born in 1999 and 2000 is 0.3% as compared to 1.7% among those born in 1986 to 1988. Overall, there is serological evidence that the universal infant HBV immunisation programme in Malaysia has been effective in reducing the rate of chronic HBV infection in individuals up to about 24 years of age. In 2018, the incidence rate and mortality rate is 14.52 and 0.21 per 100,000 population.
- Hepatitis B vaccine contains HBsAg adsorbed on aluminum hydroxide adjuvant. HBsAg is prepared from yeast cells using recombinant DNA technology.
Vaccines Available in Malaysia
Sanofi Aventis (M) Sdn Bhd/LG Chem Ltd, South Korea
- Engerix-B® (Hepatitis B)
GlaxoSmithKline Pharmaceuticals (M) Sdn Bhd/GlaxoSmithKline Biologicals S.A., Belgium
- Hepavax-Gene TF® (Hepatitis B)
Propharm (M) Sdn Bhd/Berna Biotech Korea Corporation, South Korea
- Twinrix® (Hepatitis A and B)
GlaxoSmithKline Pharmaceuticals (M) Sdn Bhd/GlaxoSmithKline Biologicals S.A., Belgium
- SII Hepatitis-B Vaccine®
SM Pharmaceuticals (M) Sdn Bhd/Serum Institute of India, India
Merck Sharp & Dohme (M) Sdn Bhd/Merck Sharp & Dohme Corp, USA
- Hepabig Injection® (Hepatitis B immune globulin)
Propharm (M) Sdn Bhd/Green Cross Corporation, South Korea
Mode of Administration
The basic immunisation regimen consists of 3 doses of vaccine, with the 1st dose at the elected date, the 2nd dose 1 month later and the 3rd dose at 6 months after the 1st dose. This schedule gives optimal protection by the 7th month and produces high antibody titres.
An accelerated schedule – with immunisation at 0, 1 and 2 months
>> will confer protection more quickly and is expected to provide better patient compliance. With this schedule, the 4th dose should be administered at 12 months, as titres after the 3rd dose are lower than those obtained after the 0, 1 and 6 months schedule.
If an even more rapid induction of protection due to exceptional circumstances is required (such as travelling to areas of high endemicity within 1 month), a schedule of 3 doses given at 0, 7 and 21 days may be used for subjects aged 20 years or older. When this schedule is applied, a 4th dose is recommended 12 months after the 1st dose.
In subjects aged 11-15 years, the vaccine may be administered according to a 0, 6 months schedule. However, protection against hepatitis B infections may not be obtained until after the 2nd dose. Therefore, this schedule should be used only when there is a low risk of hepatitis B infection during the vaccination course and when completion of the 2-dose vaccination course can be assured. If both conditions cannot be assured (for instance, patients undergoing haemodialysis, travelers to endemic regions and close contacts of infected subjects), the 3-dose or the accelerated schedule should be used.
Heplisav-B® (Dynavax) is a new single-antigen recombinant hepatitis B vaccine with a novel adjuvant. It is recommended for adults ≥ 18 years old and administered in two doses given ≥ 4 weeks apart. Pregnant women should not receive Heplisav-B® as safety data on administration during pregnancy is not available.
WHO does not recommend booster vaccination, as it has been shown that the 3-dose series of hepatitis B immunisation protects for as long as 15 years and that a protective anamnestic response occurs after exposure to HBV, even if protective antibodies have been undetectable by laboratory tests over time.
The vaccine should be given intramuscularly. It may be administered subcutaneously in patients with thrombocytopenia or bleeding disorders. It should not be administered in the buttock or intradermally, since this may result in a lower immune response.
Co-administration with Other Vaccines
A combination inactivated hepatitis A and hepatitis B vaccine (Twinrix®) is also available.
Contraindications and Adverse Effects
Hepatitis B vaccine is generally well tolerated. The most commonly reported adverse reactions are soreness, erythema and swelling at the injection site. These reactions are mild and usually subside within 2 days after vaccination. General symptoms such as fever, headache, nausea, dizziness, and fatigue rarely occur.
To date, the most frequently reported adverse events for Hepatitis B vaccines received by the National Adverse Drug Reactions Monitoring Centre (NPRA) are local site reactions such as injection site swelling rash, fever, and pruritus.
Target Groups in Malaysia
Adults who are at a higher risk of hepatitis B (see below) and:
» Have not been previously immunised should receive the full course of vaccination.
» Have not completed their primary vaccination should be given the missing doses.
The following adults at higher risk of hepatitis B and should be screened for their immune status regardless of whether they have had previous vaccination:
» Parenteral drug abusers.
» Close family contact of a case or those chronically infected.
» Patients with chronic renal failure.
» Patients with chronic liver disease.
» Healthcare workers.
» Staff and residents of residential accommodation for mentally handicapped.
» Travelers to areas of high endemicity.
» Patients attending STD and HIV clinics.
» Men who have sex with men.
» Those with multiple sex partners.
Implications for Healthcare Workers (HCWs)
- HBV infection is a well-recognised occupational risk for healthcare workers. The risk of HBV infection is primarily related to the degree of contact with blood in the workplace, particularly with percutaneous exposure. HBV infections that occur in HCWs with no history of exposure might have resulted from direct or indirect blood or body fluid exposures that inoculated HBV into the mucosal surfaces or cutaneous scratches and other lesions.
Vaccination against HBV and demonstration of immunisation before employment are strongly recommended. A study in Kuala Lumpur in 2005 revealed that only 58.4% of HCWs had completed their hepatitis B vaccination. Thus, hospital managements must make serious efforts to improve the coverage.
Pre-vaccination serology screening for previous infection is not indicated for HCWs unless the hospitals or healthcare institutions consider screening cost-effective.
>> After completion of the 3-dose vaccination series, anti-HBs testing should be tested in 1–2 months. If anti-HBs is less than 10mIU/mL (or negative), the HCW is unprotected from HBV infection and should complete a 2nd 3- dose vaccine series or be evaluated to determine if they are HBsAg-positive. Revaccinated persons should beretested at the completion of the 2nd vaccine series. Primary non-responders to vaccination who are HBsAg- negative should be considered susceptible to HBV infection and should be counselled regarding precautions to prevent HBV infection and the need to obtain HBIG prophylaxis for any known or probable parenteral exposure to HBsAg-positive blood. Persons who prove to be HBsAg-positive should be counselled accordingly.
For post-exposure prophylaxis, please refer to the section on Passive Immunisation.
Evidence for Effectiveness
Anti-HBs is the only easily measurable correlate of vaccine-induced protection using serologic assays. Anti-HBs concentration of 10mIU/mL or more, measured 1-3 months after the administration of the last dose of the primary vaccination series, is considered a reliable marker of protection against infection. This is even if anti-HBs concentrations may decline over time to less than 10mIU/mL (as it also involves the induction of memory B and T cells).
In immunocompromised patients who have ongoing exposure to HBV, annual anti-HBs testing is recommended and booster doses are required to maintain anti-HBs concentrations of 10mIU or higher.
Observational studies have shown that a primary series of hepatitis B vaccine can prevent infection for more than 20 years, despite decrease or loss of vaccine-induced anti-HBs over time.
- Hesham, R., Zamberi, S., Tajunisah, M. E., Ariza, A. & Ilina, I. (2005). Hepatitis B immunisation status among health care workers in two Kuala Lumpur hospitals. Medical Journal of Malaysia, 60(4):407-410.
- Lauer, J. L., VanDrunen, N. A., Washburn, J. W. & Balfour, H. H. Jr. (1979). Transmission of hepatitis B virus in clinical laboratory areas. Journal of Infectious Disease. 140(4):513-516.
- Lopez, C. G. (1985). Epidemiology of persistent hepatitis B virus infection. Malaysian Journal of Pathology, 7:7-10.
- The Malaysian National Centre of Adverse Drug Reactions Database [Accessed: 10 October 2019]
- MOH Malaysia. Hepatitis B Seroprevalence Study Among Children Year 3 and 4. 2009 (unpublished)
- Ministry of Health (2020, October 15) Malaysia Health Facts 2019. https://www.moh.gov.my/moh/resources/Penerbitan/Penerbitan%20Utama/HEALTH%20FACTS/Health%20Facts%202019_Booklet.pdf
- National Pharmaceutical Regulatory Agency (NPRA), Ministry of Health Malaysia. Senarai Produk Vaksin Berdaftar Dengan Pihak Berkuasa Kawalan Dadah. Received on 5 September 2019.
- Ng, K. P., Saw, T. L., Baki, A., Rozainah, K., Pang, K. W. & Ramanathan, M. (2005). Impact of Expanded Programme of Immunisation on hepatitis B infection in school children in Malaysia. Medical Microbiology and Immunology, 194:163-168.
- Van Damme P, Ward J, Shouval D, Wiersma S, Zanetti A. Hepatitis B vaccines. Vaccines, Ed Plotkin S, Ed Orenstein W and Ed O t P. Elsevier, 2013. 205-234