Hepatitis B

Advisory Committee on Immunization Practices (ACIP) Recommendations

Infants

• All medically stable infants weighing ≥2,000 grams without contraindications should receive the first dose of hepatitis B vaccine (trade names: Engerix-B®, Recombivax HB®) within 24 hours of birth.
• Certain infants at increased risk of acquisition of hepatitis B, such as infants born to hepatitis B-infected mothers or mothers with unknown status, should receive hepatitis B vaccine as soon as possible after birth along with a dose of hepatitis B immune globulin.
• The second dose should be administered a minimum of 4 weeks after the first dose and between 1-2 months of age. The third dose should be administered a minimum of 8 weeks after the second and 16 weeks after the first, between 6-18 months of age.

Children and Adolescents

• All children not previously vaccinated should receive the age-appropriate dose of hepatitis B vaccine, preferably at 11 or 12 years but up to 18 years of age.
• The usual schedule for adolescents is two doses separated by no less than 4 weeks, and a third dose at least 8 weeks from the second dose and 16 weeks from the first dose, and preferably 4- 6 months after the second dose. An approved alternative schedule for adolescents 11-15 years of age is two 1.0-mL doses of the Recombivax HB® vaccine separated by 4-6 months.

Adults

• All adults 19-59 years of age should receive hepatitis B vaccine. If receiving Recombivax HB^® or Engerix-B^®, the first two doses should be separated by at least 4 weeks and a third dose administered 4-6 months after the second dose. If receiving HEPLISAV-B™, only two doses (0.5 mL each) are given one month apart, but both doses must be HEPLISAV-B™. If receiving PREHEVBRIO, three doses (1.0 mL each) are given on a 0, 1, and 6-month schedule.
• Adults at least 60 years of age at increased risk of hepatitis B infection (including sex partners or household contacts of hepatitis B infected persons; sexually active persons not in a long-term mutually monogamous relationship; persons seeking evaluation or treatment for a sexually transmitted disease; men who have sex with men; current or recent injection drug users; residents and staff of facilities for developmentally disabled persons; health care and public safety workers at risk of exposure to blood or body fluids; persons with end-stage renal disease or diabetes mellitus; HIV-infected individuals; and international travelers to countries with high or intermediate endemnicity) or with chronic liver disease (including, but not limited to, those with hepatitis C virus [HCV] infection, cirrhosis, fatty liver disease, alcoholic liver disease, autoimmune hepatitis, and an alanine aminotransferase [ALT] or aspartate aminotransferase [AST] level greater than twice the upper limit of normal) should receive hepatitis B vaccine.
• Adults at least 60 years of age without known risk factors for hepatitis B infection or chronic liver disease may receive hepatitis B vaccine.^1,4-7

For More Information

• ACIP recommendations: http://www.cdc.gov/vaccines/hcp/acip-recs/
• Vaccine Information Statement: https://www.cdc.gov/vaccines/hcp/vis/vis-statements/hep-b.html
• Immunization schedules: http://www.cdc.gov/vaccines/schedules/index.html

Important Information for Obstetric Providers

• Hepatitis B vaccine is not routinely recommended during pregnancy.

• However, pregnancy is not a contraindication to hepatitis B vaccination.
• ACIP recommends testing all pregnant women for hepatitis B surface antigen (HBsAg), testing HBsAg-positive pregnant women for hepatitis B virus deoxyribonucleic acid (HBV DNA), and administration of hepatitis B vaccine and hepatitis B immune globulin (HBIG) for infants born to HBV-infected women within 12 hours of birth, followed by completion of the vaccine series and postvaccination serologic testing.⁴

Disease

Hepatitis B Virus (HBV) is a small, double-shelled DNA virus in the Hepadnaviridae family. HBV is transmitted via mucosal exposure to infected body fluids, often during birth, sexual contact, via blood or blood exposure, needlesticks, or injection drug use ¹. It is highly infectious to susceptible individuals exposed in these manners. Thirty percent of infected individuals in the US have no known exposures ^2,3. The incubation period averages 120 days.

Approximately 90% of infants and 50% of adult infections are asymptomatic, and when there are symptoms, they are indistinguishable from those of other types of acute viral hepatitis. Initial symptoms include malaise, anorexia, nausea, vomiting, fever, headache, myalgia, arthralgia, arthritis and dark urine. Further symptoms such as jaundice, light or gray stools, hepatic tenderness and hepatomegaly typically last 1-3 weeks, and begin 3-10 days after the onset of most initial symptoms (1-2 days following the onset of dark urine).

Most acute HBV infections result in complete recovery; however, 1-2% of cases result in fulminant hepatitis, which has a case-fatality rate of 63-93% and causes roughly 200-300 deaths in the United States annually. Up to 90% of infants infected at birth by their mothers become chronically infected, and about 25% of those chronically infected will die from cirrhosis or liver cancer. This risk of chronic infection decreases with age, to about 5% of acute infections in adults become chronic. Chronic infection is often asymptomatic until complications develop ¹.

Vaccine

Hepatitis B vaccines are yeast-derived recombinant vaccines containing HBsAg protein. There are four hepatitis B vaccines used in the United States: Recombivax HB®, which is adjuvanted with aluminum hydroxyphosphate sulfate; Engerix-B®, which is adjuvanted with aluminum hydroxide; HEPLISAV-B™, which is adjuvanted with cytosine phosphoguanine (CpG) 1018; and PREHEVBRIO™, which is adjuvanted with aluminum hydroxide. Engerix-B® and Recombivax HB® are approved for use in all ages. HEPLISAV-B™ and PREHEVBRIO™ are newer vaccines and are only approved for use in persons at least 18 years of age. HEPLISAV-B™ is administered as a two-dose series with one month between doses (0.5 mL each). PREHEVBRIO™ is administered as a three-dose series, with doses (1.0 mL each) given on a 0, 1, and 6-month schedule ^1,78.

There are also several combination vaccines that include hepatitis B vaccine. Hep A-Hep B (Twinrix®) is approved for use in persons at least 18 years of age, administered in a three-dose series at 0, 1 and 6 months. DTaP-Hep B-IPV (Pediarix®) is approved for use at 2, 4 and 6 months of age. Pediarix® cannot be used before 6 weeks of age, but can be substituted for doses 2 or 3 of hepatitis B vaccine. Infants may also receive a fourth dose of hepatitis B vaccine as part of a combination vaccine schedule ¹.

The Hib-Hep B combination vaccine Comvax® was discontinued in the United States in 2014 ⁹.

Contraindications and Precautions

Severe allergic reaction (e.g. anaphylaxis) to a previous dose or vaccine component is a contraindication to further vaccination with hepatitis B vaccine. Current moderate to severe acute illness is a precaution to any vaccination.¹

Vaccine Effectiveness

Over 90% of adults and 95% of children develop protective antibody responses after three doses of Recombivax HB® or Engerix-B®. These vaccines are > 95% effective at preventing clinical disease and the chronic carrier state after infection, and estimated to be 80-100% effective in preventing hepatitis B infections after completion of the series. Although antibody levels decline, immunologic memory induced from vaccination persists and serologic responders have been shown to be protective for at least 20 years. Follow-up studies of infants vaccinated at birth have revealed that many adolescents do not develop an anamnestic response (i.e. renewed rapid antibody production on a subsequent encounter with the same antigen) to a booster dose of vaccine, but there is no evidence of an increased rate of breakthrough disease and no routine booster dose has been recommended ¹. Studies of HEPLISAV-B™ have demonstrated higher rates of seroprotection (90.0-100.0%) compared to Engerix-B® (70.5-90.2%) ⁷.

Studies of PREHEVBRIO™ have also demonstrated higher rates of seroprotection (91.4%) compared to Engerix-B® 76.5%) ¹⁰.

Vaccine Safety

Anaphylaxis occurs approximately once per every 1.1 million doses of hepatitis B vaccine administered. Alopecia has been suggested to be rarely associated with hepatitis B vaccination. No causal association between any chronic illnesses and hepatitis B vaccine have been shown ¹.

The safety profiles of HEPLISAV-B™ ^7,11 and PREHEVBRIO™ ¹⁰ were found to be comparable to Engerix-B® in phase III clinical trials.

Considerations in Pregnancy

Perinatal transmission from mother to infant at birth is very efficient. If a mother is positive for both hepatitis B surface antigen (HBsAg) and hepatitis B e antigen (HBeAg) and postexposure prophylaxis is not administered, 70%–90% of infants will become infected. If the mother is positive only for HBsAg, the risk of perinatal transmission is about 10%. Up to 90% of infant HBV infections will become chronic, and of these, 25% will die from hepatitis B related disease ^1,5,6,12.

Therefore, prevention of perinatal HBV infection is of the utmost importance. All pregnant individuals should be screened for hepatitis B surface antigen (HBsAg) and infants born to women who are HBsAg-positive should receive postexposure prophylaxis with hepatitis B immune globulin (HBIG), as well as the hepatitis B vaccine series starting at birth. Not only does hepatitis B vaccine protect against future hepatitis B infection, it is also 70%–95% effective as a postexposure prophylaxis in preventing mother-to-infant HBV transmission when the first dose is administered within 24 hours after birth followed by the completion of the three-dose series ^1,5,6,12. The universal birth dose policy for hepatitis B vaccine provides an important safety net for when infected mothers are not identified during pregnancy or when there are communication errors regarding infection status. Vaccination on schedule also prevents potential HBV transmission from infected household contacts to the infant during the particularly vulnerable first months of life ¹³.

The ACIP now also recommends testing HBsAg-positive pregnant individuals for hepatitis B virus deoxyribonucleic acid (HBV DNA); postvaccination serologic testing for infants whose mother’s HBsAg status remains unknown indefinitely; and single-dose revaccination for infants born to HBsAg-positive women not responding to the initial vaccine series ⁴. Please refer to the most recent ACIP recommendations ⁴ as well as the American Association for the Study of Liver Diseases (AASLD) guidelines for further information on reducing perinatal HBV transmission through maternal antiviral therapy ^14,15.

Pregnancy is not a contraindication to hepatitis B vaccination. This is because the vaccine contains HBsAg, which is not infectious, and because limited data suggest that developing fetuses are not at risk for adverse events when the vaccine is administered during pregnancy ^1,6,12.

Talking Points

1. Briefly address specific concerns

2. Discuss Disease Risk

• Hepatitis B is a highly infectious virus that is spread through bodily fluids.
• Hepatitis B can cause vomiting, fever, nausea, and yellowing of the skin. In some cases, it can cause liver disease, liver cancer, and death.
• You may not even know when someone is infected with hepatitis B, as many people do not have any symptoms.
• It is very easy for a pregnant individual to pass hepatitis B on to her baby during delivery.

3. Explain Vaccine Effectiveness

• The good news about Hepatitis B is that there are effective vaccines.
• Hepatitis B vaccines are more than 95% efficacious.

References

1.         Epidemiology and Prevention of Vaccine-Preventable Diseases. Washington D.C.: Centers for Disease Control and Prevention, 2015.

2.         Zuckerman JN. Protective efficacy, immunotherapeutic potential, and safety of hepatitis B vaccines. Journal of medical virology 2006; 78(2): 169-77.

3.         Ocama P, Opio CK, Lee WM. Hepatitis B virus infection: current status. The American journal of medicine 2005; 118(12): 1413.

4.         Schillie S, Vellozzi C, Reingold A. Prevention of Hepatitis B Virus Infection in the United States: Recommendations of the Advisory Committee on Immunization Practices. MMWR Morbidity and mortality weekly report 2018; 67(1): 1–31.

5.         Mast EE, Margolis HS, Fiore AE, Brink EW, Goldstein ST, Wang SA, Moyer LA, Bell BP, Alter MJ. A comprehensive immunization strategy to eliminate transmission of hepatitis B virus infection in the United States: recommendations of the Advisory Committee on Immunization Practices (ACIP) part 1: immunization of infants, children, and adolescents. MMWR Recommendations and reports : Morbidity and mortality weekly report Recommendations and reports 2005; 54(Rr-16): 1-31.

6.         Mast EE, Weinbaum CM, Fiore AE, Alter MJ, Bell BP, Finelli L, Rodewald LE, Douglas JM, Jr., Janssen RS, Ward JW. A comprehensive immunization strategy to eliminate transmission of hepatitis B virus infection in the United States: recommendations of the Advisory Committee on Immunization Practices (ACIP) Part II: immunization of adults. MMWR Recommendations and reports : Morbidity and mortality weekly report Recommendations and reports 2006; 55(Rr-16): 1-33; quiz CE1-4.

7.         Schillie S, Harris A, Link-Gelles R, Romero J, Ward J, Nelson N. Recommendations of the Advisory Committee on Immunization Practices for Use of a Hepatitis B Vaccine with a Novel Adjuvant. MMWR Morbidity and mortality weekly report 2018; 67(15): 455-8.

8.         Weng MK, Doshani M, Khan MA, Frey S, Ault K, Moore KL, Hall EW, Morgan RL, Campos-Outcalt D, Wester C, Nelson NP. Universal Hepatitis B Vaccination in Adults Aged 19-59 Years: Updated Recommendations of the Advisory Committee on Immunization Practices – United States, 2022. MMWR Morbidity and mortality weekly report 2022; 71(13): 477-83.

9.         Immunization Action Coalition. Merck discontinues production of Comvax vaccine (Hib-HepB). 2014. http://www.immunize.org/express/issue1136.asp#IACX6 (accessed March 2018).

10.       Vesikari T, Finn A, van Damme P, Leroux-Roels I, Leroux-Roels G, Segall N, Toma A, Vallieres G, Aronson R, Reich D, Arora S, Ruane PJ, Cone CL, Manns M, Cosgrove C, Faust SN, Ramasamy MN, Machluf N, Spaans JN, Yassin-Rajkumar B, Anderson D, Popovic V, Diaz-Mitoma F, Group CS. Immunogenicity and Safety of a 3-Antigen Hepatitis B Vaccine vs a Single-Antigen Hepatitis B Vaccine: A Phase 3 Randomized Clinical Trial. JAMA Network Open 2021; 4(10): e2128652-e.

11.       Hyer R, McGuire DK, Xing B, Jackson S, Janssen R. Safety of a two-dose investigational hepatitis B vaccine, HBsAg-1018, using a toll-like receptor 9 agonist adjuvant in adults. Vaccine 2018; 36(19): 2604-11.

12.       Leads from the MMWR. Prevention of perinatal transmission of hepatitis B virus: prenatal screening of all pregnant women for hepatitis B surface antigen. Jama 1988; 260(2): 165, 9-70.

13.       Implementation of newborn hepatitis B vaccination–worldwide, 2006. MMWR Morbidity and mortality weekly report 2008; 57(46): 1249-52.

14.       Terrault NA, Bzowej NH, Chang KM, Hwang JP, Jonas MM, Murad MH. AASLD guidelines for treatment of chronic hepatitis B. Hepatology (Baltimore, Md) 2016; 63(1): 261-83.

15.       Terrault NA, Lok ASF, McMahon BJ, Chang KM, Hwang JP, Jonas MM, Brown RS, Jr., Bzowej NH, Wong JB. Update on prevention, diagnosis, and treatment of chronic hepatitis B: AASLD 2018 hepatitis B guidance. Hepatology (Baltimore, Md) 2018; 67(4): 1560-99.