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Hepatitis B virus immunization in infants, children, and adolescents

Hepatitis B virus immunization in infants, children, and adolescents
Literature review current through: May 2024.
This topic last updated: May 11, 2023.

INTRODUCTION — Hepatitis B virus (HBV) immunization before HBV exposure is the most effective means to prevent HBV transmission. Hepatitis B immunization in infants, children, and adolescents will be discussed here, focusing on immunization of infants, children, and adolescents (<18 years) in the United States. Our recommendations are generally consistent with those of the Advisory Committee on Immunization Practices, the American Academy of Pediatrics, the American Academy of Family Physicians and the American Association for the Study of Liver Diseases.

HBV infection in children and adolescents and Hepatitis B immunization in adults (≥18 years) are discussed separately. (See "Clinical manifestations and diagnosis of hepatitis B virus infection in children and adolescents" and "Management of hepatitis B virus infection in children and adolescents" and "Hepatitis B virus immunization in adults".)

HEPATITIS B INFECTION — HBV is a deoxyribonucleic acid (DNA) hepadnavirus. The viral particle is composed of an outer lipoprotein envelope, which contains hepatitis B surface antigen (HBsAg), and an inner nucleocapsid, which consists of hepatitis B core antigen (HBcAg) [1].

HBV can be transmitted vertically from mother to infant during labor or delivery, through sexual intercourse, or by exposure to contaminated blood or body fluids. In utero transmission is uncommon. Infants born to HBsAg-positive women are at increased risk of HBV infection. Adolescents also are at increased risk as a result of sexual behavior or injection drug use. (See "Epidemiology, transmission, and prevention of hepatitis B virus infection", section on 'Transmission of HBV'.)

Each year in the United States an estimated 25,000 infants are born to women who are HBV carriers [2]. As many as 90 percent of these infants will acquire acute HBV infection if no preventive measures are taken [3,4]. Acquisition of HBV during infancy or early childhood is associated with an increased risk of developing chronic HBV infection compared with infection later in life (figure 1). Approximately 25 percent of people infected with chronic HBV infection during infancy die prematurely from cirrhosis or liver cancer [5-7]. Most people with chronic HBV infection remain asymptomatic until the onset of cirrhosis or end-stage liver disease and may be unaware of their infection, increasing the risk of transmission to household, sexual, or needle-sharing contacts. (See "Hepatitis B and pregnancy", section on 'Mother-to-child transmission' and "Hepatitis B virus: Clinical manifestations and natural history", section on 'Sequelae and prognosis of chronic HBV infection'.)

VACCINE FORMULATIONS — The vaccines available in the United States use recombinant DNA technology to express hepatitis B surface antigen in yeast cells. They do not contain thimerosal [8-11].

Single antigen vaccines – Two single antigen (ie, monovalent) recombinant hepatitis B vaccines (conventional) are available for use in children (<18 years) in the United States [1,12]:

Engerix-B and

Recombivax HB

These hepatitis B (HepB) vaccines are supplied in different concentrations and have different doses (table 1). They can be used interchangeably [13], except that only the adult formulation of Recombivax HB can be used for the two-dose series in adolescents age 11 through 15 years [1].

Vaccinations available only for adults ≥age 18 years (ie, recombinant hepatitis B vaccine [CpG-adjuvanted], Heplisav-B; recombinant hepatitis B vaccine [trivalent], Prehevbrio) are discussed separately. (See "Hepatitis B virus immunization in adults", section on 'Single-antigen vaccines'.)

Combination vaccines – Recombinant HepB vaccine is a component in three combination vaccines, which can be used if the patient is due for the other vaccine components:

Pediarix – Diphtheria and tetanus toxoids and acellular pertussis (DTaP), HepB (Engerix-B 10 mcg/mL), and inactivated poliovirus vaccine (IPV) are typically administered at two, four, and six months of age; the DTaP-HepB-IPV combination vaccine should not be administered before six weeks or after seven years of age.

Vaxelis – The combination DTaP, IPV, Haemophilus influenzae type b, and HepB recombinant vaccine is recommended for use at two, four, and six months of age and approved for use as a three-dose series in children six weeks through four years of age [14,15].

Twinrix – Hepatitis A and hepatitis B (Engerix-B 20 mcg); this vaccine is approved for individuals ≥18 years of age. (See "Hepatitis B virus immunization in adults".)

Another combination vaccine (Comvax), which contained HepB vaccine and Haemophilus influenzae type b conjugate vaccine, was discontinued in 2014 [16].

Interchangeability – The same brand of vaccine should be used whenever it is feasible, particularly for the first three doses in the series [1,12,17]. If this is not feasible (eg, due to vaccine availability), an opportunity to administer vaccines to an eligible child should not be missed because the brand used for earlier doses is not available (or not known). Limited data suggest that using different brands to complete the primary series does not adversely affect vaccine safety or immunogenicity, but additional data supporting the interchangeability of acellular pertussis-containing HepB combination vaccines are necessary [18].

Storage – HepB vaccine should be refrigerated at a temperature between 36 and 46°F (2 and 8°C) [19].

ROUTINE INFANT IMMUNIZATION — We recommend immunization against HBV for all infants, as recommended by the Advisory Committee on Immunization Practices, American Academy of Pediatrics, American Academy of Family Physicians, and the World Health Organization (WHO) [1,12,20-22]. Hepatitis B (HepB) vaccine is >90 percent efficacious in preventing HBV infection and has few adverse effects. (See 'Efficacy and effectiveness' below and 'Adverse reactions' below.)

In the United States — In the United States, the timing of the first dose of HepB vaccine and the need for hepatitis B immune globulin (HBIG) are determined by the mother's hepatitis B surface antigen (HBsAg) status, the infant's gestational age, and the infant's birth weight (table 2A-B) [1,23].

Testing for HBsAg should be performed on all women at the first prenatal visit. (See "Hepatitis B and pregnancy", section on 'Maternal screening'.)

HBsAg-positive mother or mother with other evidence of HBV infection — As soon as possible and within 12 hours after birth, infants born to women who are HBsAg-positive or women whose prenatal HBsAg results are not available at the time of delivery but who have other evidence of maternal HBV infection (eg, presence of hepatitis B deoxyribonucleic acid, positive hepatitis e antigen, known chronic hepatitis B infection) should receive (algorithm 1) [1,23]:

The first dose of single-antigen HepB vaccine intramuscularly (IM)

HBIG 0.5 mL IM

HepB vaccine and HBIG should be administered at different anatomic sites and regardless of birth weight or maternal antiviral therapy for high hepatitis B viral loads during pregnancy. Infants who receive appropriate immunoprophylaxis may breastfeed immediately after birth.

The risk of perinatal transmission among infants born to HBsAg-positive mothers is as high as 90 percent without immunoprophylaxis [24,25].

The schedule for subsequent doses depends upon the infant's birth weight (table 2A-B):

Birth weight ≥2 kg (4.4 pounds) – The second and third doses should be given at one and six months of age, respectively.

Birth weight <2 kg (4.4 pounds) – Three additional doses should be given (at one, two to three, and six months of age or at two, four, and six months of age).

Testing for HBsAg and antibody to HBsAg should be performed at 9 to 12 months of age. (See 'Postvaccination serology' below.)

The benefits of prompt administration of HepB vaccine and HBIG and appropriate completion of the HepB vaccine series in preventing perinatal HBV infection in infants born to HBsAg-positive mothers have been demonstrated in randomized trials and in cohort studies [26-29]. In a meta-analysis of three randomized trials, compared with placebo/no intervention, the combination of HepB vaccine and HBIG reduced HBV infection in infants born to HBsAg-positive women (4 versus 57 percent, relative risk [RR] 0.08, 95% CI 0.03-0.17) [26]; in a meta-analysis of 10 randomized trials, the combination of HepB vaccine and HBIG was superior to HepB vaccine alone in reducing perinatal HBV infection (13 versus 24 percent, RR 0.54, 95% CI 0.41-0.73). In prospective surveillance studies of infants born to women with HBV infection who received HBIG and HepB vaccine and had postvaccination serologic testing, perinatal HBV infection occurred in <2 percent [27,28]. The risk of HBV was increased in infants who received <3 doses of HepB vaccine compared with those who received ≥3 doses [27].

The effectiveness of maternal antiviral therapy for high hepatitis B viral load during the third trimester of pregnancy combined with infant immunoprophylaxis on perinatal transmission are discussed separately. The effectiveness of maternal treatment without infant immunoprophylaxis is unknown [23]. (See "Hepatitis B and pregnancy", section on 'Prevention of mother-to-child transmission'.)

HBsAg-negative mother, birth weight ≥2 kg — If the mother is HBsAg negative and the birth weight is ≥2 kg (4.4 pounds), the recommended schedule for HepB vaccine is as follows (table 2A) [1,23]:

First dose – During the birth hospitalization, within 24 hours of birth (algorithm 2)

Second dose – At 1 to 2 months of age

Third dose – At 6 to 18 months of age (must be given at ≥24 weeks of age)

Only single-antigen HepB vaccine can be used for the birth dose. Either single-antigen HepB vaccines or HepB-containing combination vaccines can be used for the second and third doses if the infant is ≥6 weeks old [1,12]. Infants who receive the combination diphtheria and tetanus toxoids and acellular pertussis (DTaP)-HepB-inactivated poliovirus vaccine (IPV) vaccine to complete the HepB series may receive a total of four doses (because DTaP and IPV are typically administered at two, four, and six months of age). In a randomized trial, receiving single-antigen HepB vaccine at birth in addition to HepB-containing combination vaccine at two, four, and six months of age did not increase the reactogenicity of a HepB-containing combination vaccine [30]. Preterm infants with birth weight ≥2 kg (4.4 pounds) produce an immune response to the HepB vaccine comparable to that in term infants [31,32].

The minimum age for the final (third or fourth) dose of HepB vaccine is 24 weeks [1]. The minimum interval between the second and third doses of a three-dose series or the third and fourth dose of a four-dose series is eight weeks. Longer intervals between the last two doses may result in higher antibody levels or longer duration of protective antibody [33-36] but increase the risk for acquisition of HBV in persons who have a delayed response to vaccination. Preterm infants with birth weight ≥2 kg (4.4 pounds) produce an immune response to the HepB vaccine comparable to that in term infants [31,32].

Giving the first dose during the birth hospitalization is recommended because the birth dose serves as a "safety net" to prevent perinatal infection in infants born to HBsAg-positive mothers who are not identified (eg, because of errors in testing or failures in reporting of test results) and infants at risk for HBV infection after the perinatal period [1]. In a cohort study of infants born to HBsAg-positive mothers, delay in administration of the first dose of HepB vaccine beyond one week of age was associated with increased risk of transmission (4.7 versus 22.2 to 33.3 percent) [37]. In addition, in observational studies, receipt of the birth dose of HepB vaccine has been associated with higher rates of on-time completion of the HepB vaccine series and timely receipt of other infant immunizations [38-40], without compromising immunogenicity [36].

HBsAg-negative mother, birth weight <2 kg — If the mother is HBsAg-negative, the birth weight is <2 kg (4.4 pounds), and the infant is medically stable, the infant is immunized at one month of age or at hospital discharge if discharge occurs before one month of age (table 2B and algorithm 2) [1,12,23].

HepB vaccine is less immunogenic in preterm infants with birth weights <2 kg (4.4 pounds) than in term infants [31,41-43]. However, preterm infants who are medically stable respond to HepB vaccine by one month of age regardless of birth weight or gestational age [31,32,43-47].

Immunization of low-risk preterm, low birth weight infants by one month of age permits greater flexibility for initiating the routine immunization schedule during hospitalization, may decrease the number of simultaneous immunizations at six to eight weeks of age, provides timely protection for infants who may require blood products or surgery, and increases the likelihood that HepB vaccine and other recommended childhood vaccines will be completed on time [38-40].

Mother's HBsAg status unknown, birth weight ≥2 kg — If the mother's HBsAg status is unknown and she has no evidence suggestive of hepatitis B infection, and the infant's birth weight is ≥2 kg (4.4 pounds), the first dose of single-antigen HepB vaccine should be administered within 12 hours of birth (table 2A) while testing the mother to determine her HBsAg status (algorithm 2) [1]. The schedule for the remaining doses of HepB vaccine and the need for HBIG depends upon the mother's HBsAg status once it is determined. If she is found to be HBsAg-positive, HBIG 0.5 mL should be given by one week of age. If maternal status remains unknown, HBIG 0.5 mL should be administered at hospital discharge or within seven days (whichever is first) [12]. (See 'HBsAg-positive mother or mother with other evidence of HBV infection' above and 'HBsAg-negative mother, birth weight ≥2 kg' above.)

Mother's HBsAg status unknown, birth weight <2 kg — If the mother's HBsAg status is unknown and the infant's birth weight is <2 kg (4.4 pounds), the infant should receive single-antigen-HepB vaccine within 12 hours of birth and HBIG 0.5 mL within 12 hours of birth if maternal status cannot be determined by that time or is positive (algorithm 2 and table 2B). The dose of HepB vaccine that is administered within 12 hours of birth is not counted; the infant will require three additional doses of HepB vaccine to complete the immunization series. The schedule for the three doses and subsequent management vary according to the mother's HBsAg status. Infants whose mother's HBsAg status will remain unknown indefinitely (eg, those who were abandoned or safely surrendered after home birth) should be managed as if the mother was HBsAg-positive. (See 'HBsAg-positive mother or mother with other evidence of HBV infection' above and 'HBsAg-negative mother, birth weight <2 kg' above.)

In other countries — Routine immunization schedules vary from country to country. Schedules for individual countries are available through the WHO.

Efficacy and effectiveness — The efficacy and effectiveness of HepB immunization vary depending upon the outcome (eg, protection from disease or levels of antibody correlated with protection) and the number of doses received.

Between the early 1990s, when HepB vaccine was added to the routine infant immunization schedule in the United States, and 2004, the rate of acute HBV in children and adolescents <19 years in the United States decreased by 94 percent (figure 2).

The long-term efficacy of infant HepB immunization programs was demonstrated in 30-year follow-up of a cluster randomized trial comparing universal neonatal HepB vaccine and no vaccine; none of the study participants received HBIG [48]. Neonatal hepatitis B vaccine protected against developing primary liver cancer (efficacy 84 percent, 95% CI 23-97), mortality from infant fulminant hepatitis (efficacy 69 percent, 95% CI 34-85), and severe end-stage liver disease (efficacy 70 percent, 95% CI 15-89).

The long-term effectiveness of infant HepB immunization programs was demonstrated in 30-year follow-up of the national program in Taiwan, which was introduced for high-risk infants in 1984 and expanded to include all newborns in 1986 and preschool-and school age children in 1988 [49]. Coverage rates were >88 percent [49]. Between 1977 to 1980 and 2009 to 2011, the incidence of hepatocellular carcinoma among individuals 5 to 29 years of age declined by >80 percent (from 1.1 to 0.09 per 100,000 person-years). Hepatitis B-related mortality declined by >90 percent (from 5.8 to 0.2 per 100,000 person-years for infant fulminant hepatitis, from 0.65 to 0.02 per 100,000 person-years for chronic liver disease, and from 0.81 to 0.05 per 100,000 person-years for hepatocellular carcinoma).

Duration of immunity — Vaccine-induced immunity to hepatitis B virus is long lasting [50-52]. Routine booster doses of HepB vaccine are not necessary for children and adolescents with normal immune status [1]. The need for additional doses of HepB vaccine in immune-compromised children and adolescents is discussed below. (See 'Immune-compromised patients' below.)

In a cohort of 423 children from an area of low HBV endemicity who completed the HepB vaccination series by 12 months of age, >90 percent demonstrated a protective response to a challenge dose of vaccine at age 16 through 19 years [53]. A similar rate of response (88 percent) was noted 30 years after completion of the HepB vaccine series in 85 Alaska Native adults and children [50].

VACCINE ADMINISTRATION — Hepatitis B (HepB) vaccine dose (and corresponding volume) varies with the age of the recipient and whether they are receiving hemodialysis or are immune compromised (table 1). If an adult dose of the vaccine is administered to an infant, the dose can be counted as valid and does not need to be repeated; the next dose should be given according to the routine schedule [54].

HepB vaccines are administered intramuscularly (IM) (table 3) [55]. HepB vaccine administered by any route other than IM should not be counted as valid and should be repeated. Administration of immunizations in children with bleeding disorders is discussed separately. (See "Standard immunizations for children and adolescents: Overview", section on 'Other special circumstances'.)

HepB vaccines typically are administered in the anterolateral thigh (for children <3 years) or deltoid (for children ≥3 years) (table 3) [55]. HepB administered at any site other than the deltoid or anterolateral thigh should not be counted as valid and should be repeated [56-59]. (See 'Catch-up immunization' below.)

Different limbs should be used if HepB vaccine and hepatitis B immune globulin (HBIG) are administered at the same time (ie, same day, same clinic visit) [55]. The injections may be administered in any order. There is no minimum interval between administration of HepB vaccine and HBIG if they are not administered at the same time.

HepB vaccine may be administered at the same clinic visit as other routine childhood immunizations (figure 3A-B) [55,60].

CATCH-UP IMMUNIZATION

Target groups — Catch-up hepatitis B (HepB) vaccine is indicated for [1,12]:

All children and adolescents <19 years who are unvaccinated or incompletely vaccinated against HBV (table 4) (see "Epidemiology, transmission, and prevention of hepatitis B virus infection", section on 'Transmission of HBV')

Children and adolescents with unknown or uncertain vaccination status

Children and adolescents who received doses of HepB vaccine that were administered inappropriately, unless serologic testing (if performed) indicates that they responded adequately (see 'Postvaccination serology' below)

Inappropriate administration includes:

Intervals that were too short (eg, <4 weeks between the first and second dose; <8 weeks between the second and third dose; or <16 weeks between the first and third dose); doses administered four or fewer days less than these intervals are considered valid [1]

Receipt of the final dose of the primary infant series at <24 weeks of age; doses administered four or fewer days less than 24 weeks (ie, at ≥164 days) are considered valid [1]

Administration by a route other than intramuscular

Administration at a site other than the anterolateral thigh or deltoid

Need for prevaccination screening — Prevaccination serologic testing is not routinely necessary before initiating or resuming HepB immunization in children or adolescents. The risk of adverse effects is not increased in persons who are immune to HBV because of past infection or immunization [1].

However, in patients at high risk of HBV infection (table 4), prevaccination testing can identify acute or chronic HBV infection or immunity to HBV infection. Serologic testing should not be a barrier to immunization [61]. In most cases the first dose of vaccine should be administered immediately after blood is obtained for serology (ie, without waiting for results). When serologic testing and HepB vaccination are to be performed on the same day, blood for serology should be obtained before immunization. Transient HBsAg positivity (<21 days) has been reported following HepB vaccination [62-64]. (See "Clinical manifestations and diagnosis of hepatitis B virus infection in children and adolescents", section on 'Screening'.)

Schedule — The HepB vaccine series does not need to be restarted if it was interrupted [1]. The remaining doses should be administered as soon as possible, adhering to the minimum intervals: 4 weeks between the first and second dose; 8 weeks between the second and third dose; and 16 weeks between the first and third dose.

Unvaccinated adolescents age 11 through 15 years have the option of a two-dose series using the adult formulation of the Recombivax HB vaccine (10 mcg/1 mL per dose) (table 1); the two doses are administered four to six months apart [65]. Both doses must be administered before 16 years of age. If the second dose is not administered until after the 16th birthday, a pediatric formulation should be used for the second dose, and the adolescent should receive a third dose (pediatric formulation) at least 8 weeks after the second dose and 16 weeks after the first dose. The need to achieve completion of the vaccine series should be considered when choosing the two- or three-dose schedule for adolescents 11 through 15 years of age.

SPECIAL POPULATIONS

Immune-compromised patients — Issues related to hepatitis B immunization for immunocompromised patients, including those with human immunodeficiency virus (HIV) infection, are discussed separately. (See "Immunizations in hematopoietic cell transplant candidates, recipients, and donors", section on 'Hepatitis B' and "Immunizations in solid organ transplant candidates and recipients", section on 'Hepatitis B' and "Immunizations in patients with inborn errors of immunity", section on 'Killed, inactivated, mRNA, or subcomponent vaccines' and "Immunizations in persons with HIV", section on 'Hepatitis B vaccine'.)

Travelers to HBV-endemic areas — Hepatitis B vaccine for travelers to countries with intermediate or high hepatitis B virus endemicity (table 5) is discussed separately. (See "Immunizations for travel", section on 'Hepatitis B vaccine'.)

CONTRAINDICATIONS AND PRECAUTIONS — HBV vaccination is contraindicated in individuals with a history of hypersensitivity to yeast or to any vaccine component (table 6) [1,55].

Acute moderate to severe illness is a precaution to HBV vaccination [55]. Vaccination generally should be postponed until after recovery to avoid superimposing adverse effects of the vaccine on the underlying illness and diagnostic confusion between manifestations of the underlying illness and adverse effects. However, decisions should be individualized.

Vaccination is not contraindicated in persons with a history of multiple sclerosis, Guillain-Barré syndrome, autoimmune disease, or other chronic disorders; nor is it contraindicated in pregnancy [1,55,66].

ADVERSE REACTIONS — Hepatitis B (HepB) vaccines are safe. The most frequently reported side effects are pain at the injection site in 3 to 29 percent, erythema in 3 percent, and fever >37.7°C (99°F) in 1 to 6 percent [1]. Administration of the first dose during the birth hospitalization has not been associated with increased rates of newborn sepsis evaluations [67]. In a large cohort, the risk of anaphylaxis after a HepB-containing vaccine was 1 per 1.1 million doses (95% CI 0.1-3.9) [68].

In the United States, any clinically significant or unexpected adverse events that occur after administration of HepB vaccine should be reported to the Vaccine Adverse Event Reporting System (telephone number 1-800-822-7967). (See "Standard immunizations for children and adolescents: Overview", section on 'Reporting adverse events'.)

POSTVACCINATION SEROLOGY — Serologic testing to assess antibody response to hepatitis B (HepB) vaccine usually is not necessary for immunocompetent children and adolescents. However, it should be performed in specific populations, including [1]:

Infants — Postvaccination serology should be obtained in infants born to [1]:

Women who are HBsAg-positive

Women whose prenatal HBsAg results were not available at the time of delivery but who have other evidence suggestive of hepatitis B infection (eg, presence of hepatitis B deoxyribonucleic acid, positive hepatitis B e antigen, known to have chronic hepatitis B)

Women whose HBsAg-status cannot be determined (eg, infants who were abandoned or safely surrendered shortly after birth)

Postvaccination serology (both HBsAg and antibody to HBsAg [anti-HBs] (table 7)) should be obtained after receiving ≥3 doses of HepB vaccine, usually at 9 to 12 months of age or one to two months after the last dose of HepB vaccine if immunization is delayed [1]. Obtaining serology soon after the vaccine series is completed is supported by observational studies demonstrating that levels of anti-HBs decreased with increasing intervals from the last dose of HepB vaccine, resulting in unnecessary revaccination when serology was obtained later [69,70].

Serology should not be performed before nine months of age because hepatitis B immune globulin (HBIG) may still be present; it should not be performed sooner than four weeks after the last dose of HepB vaccine because of the possibility of transient (<21 days) HBsAg-positivity related to the vaccine [62,63].

HBsAg-positive infants – Infants who are HBsAg-positive at any time during postvaccination testing should be referred for evaluation of chronic liver disease (algorithm 1). Household contacts who have not been vaccinated against HBV should be vaccinated. (See "Clinical manifestations and diagnosis of hepatitis B virus infection in children and adolescents" and "Management of hepatitis B virus infection in children and adolescents".)

HBsAg-negative infants – Management of infants who are HBsAg-negative depends upon the concentration of anti-HBs (algorithm 1):

Anti-HBs ≥10 milli-international units (mIU)/mL – Infants who are HBsAg-negative and have anti-HBs concentration ≥10 mIU/mL are immune to HBV. Additional doses of HepB vaccine and serologic testing are not necessary.

Anti-HBs <10 mIU/mL – Infants whose anti-HBs is <10 mIU/mL remain susceptible to HBV (table 7).

-Preferred regimen – The preferred regimen for infants who remain susceptible after the primary infant series is one dose of HepB vaccine followed by measurement of anti-HBs and HBsAg one to two months later [1]. This approach is supported by observational studies in which >94 percent of infants born to HBsAg-positive women achieved anti-HBs ≥10 mIU/mL with one additional dose of HepB vaccine [70-72]. Compared with the alternative regimen, it reduces the number of vaccine doses, the duration of case management, and cost for most infants.

HBsAg-negative infants whose anti-HBs remains <10 mIU/mL after the first additional dose of HepB vaccine should receive two more doses, separated by at least eight weeks, with measurement of anti-HBs and HBsAg one to two months later. In a cohort study, all 45 HBV-susceptible children who did not respond to perinatal HepB immunization responded to a second HepB vaccine series, and >70 percent had protective titers four years later [73].

-Alternative regimen – An alternative regimen for infants who remain susceptible after the primary infant series is three doses of HepB vaccine (at zero, one to two, and six months) followed by measurement of anti-HBs and HBsAg one to two months after the third dose. The alternative regimen may be warranted depending on clinical circumstances or caregiver preference.

HBsAg-negative children whose anti-HBs levels remain <10 mIU/mL after two complete series of HepB vaccines are considered to be "nonresponders" and susceptible to HBV. Available data do not suggest a benefit from additional doses of HepB vaccine.

Caregivers of nonresponders should receive information about precautions to prevent HBV infection, and the nonresponders should receive appropriate postexposure prophylaxis if they are exposed. (See "Epidemiology, transmission, and prevention of hepatitis B virus infection", section on 'Prevention'.)

In the United States, postvaccination serology results should be reported to perinatal hepatitis B program coordinators who can assist caregivers in assuring infant protection [28].

Older children and adolescents

Hemodialysis patients – Hemodialysis patients may have a reduced response to HepB vaccine. Serologic testing (anti-HBs) one to two months after administration of the last dose of the primary HepB vaccine series is recommended to determine the need for revaccination [1].

In addition, we obtain annual anti-HBs testing for hemodialysis patients and administer a booster dose of HepB vaccine when the anti-HBs concentration is <10 mIU/mL, in agreement with the United States Advisory Committee on Immunization Practices (ACIP), American Academy of Pediatrics (AAP), and the American Association for the Study of Liver Diseases [1,12,74].

Immune-compromised patients – The immune response to HepB vaccine is reduced in children who are immune compromised [75-80]. However, there is no standard approach to postvaccination testing and provision of booster doses. Annual testing for anti-HBs and provision of a booster dose of HepB vaccine when anti-HBs concentration is <10 mIU/mL is a reasonable strategy for prevention of HBV infection in immune-compromised children and adolescents with ongoing risk of HBV exposure and is suggested by the ACIP and AAP [1,12].

Additional considerations regarding HepB immunization for immune-compromised patients are discussed separately. (See "Immunizations in hematopoietic cell transplant candidates, recipients, and donors", section on 'Hepatitis B' and "Immunizations in solid organ transplant candidates and recipients", section on 'Hepatitis B' and "Immunizations in patients with inborn errors of immunity", section on 'Killed, inactivated, mRNA, or subcomponent vaccines' and "Immunizations in persons with HIV", section on 'Hepatitis B vaccine'.)

Sexual partners of HBsAg-positive persons – Sexual partners of HBsAg-positive persons are at risk of recurrent exposure to HBV, and it is important to make sure that they have a protective response to the primary vaccine series.

Those who have anti-HBs concentrations ≥10 mIU/mL are considered immune to HBV and do not require additional testing (unless they are immune compromised).

Those who have anti-HBs concentrations <10 mIU/mL should be revaccinated according to an age-appropriate schedule and have repeat measurement of anti-HBs one to two months after completion. Those who do not respond to a second series of vaccines should be tested for HBsAg.

-Those who are HBsAg-positive should be referred for evaluation of chronic liver disease. Their household contacts who have not been vaccinated against HBV should be vaccinated. (See "Clinical manifestations and diagnosis of hepatitis B virus infection in children and adolescents" and "Management of hepatitis B virus infection in children and adolescents".)

-Those who are HBsAg-negative should be considered to be susceptible to HBV. They should receive information about precautions to prevent HBV infection and should receive appropriate postexposure prophylaxis if they are exposed. (See "Epidemiology, transmission, and prevention of hepatitis B virus infection", section on 'Prevention'.)

POSTEXPOSURE IMMUNIZATION — Postexposure HepB immunization (with or without adjunctive hepatitis B immune globulin) is recommended for unvaccinated or incompletely vaccinated children and adolescents with exposure to blood or infectious secretions (eg, bite, needlestick, sexual assault). (See "Epidemiology, transmission, and prevention of hepatitis B virus infection", section on 'Prevention'.)

RESOURCES — Resources related to immunization in infants and children include:

The American Academy of Pediatrics

The Centers for Disease Control and Prevention

The Immunization Action Coalition

Vaccine information statement for hepatitis B vaccine

The World Health Organization

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Prevention of hepatitis B virus infection" and "Society guideline links: Immunizations in children and adolescents".)

INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5th to 6th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10th to 12th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.

Here are the patient education articles that are relevant to this topic. We encourage you to print or email these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient education" and the keyword[s] of interest.)

Basics topics (see "Patient education: Hepatitis B (The Basics)" and "Patient education: Vaccines for babies and children age 0 to 6 years (The Basics)" and "Patient education: Vaccines for children age 7 to 18 years (The Basics)")

Beyond the Basics topics (see "Patient education: Hepatitis B (Beyond the Basics)" and "Patient education: Why does my child need vaccines? (Beyond the Basics)" and "Patient education: Vaccines for infants and children age 0 to 6 years (Beyond the Basics)" and "Patient education: Vaccines for children age 7 to 18 years (Beyond the Basics)")

SUMMARY AND RECOMMENDATIONS

Routine infant immunization – We recommend universal hepatitis B (HepB) immunization for infants (Grade 1A). In the United States, HepB vaccine usually is administered at birth, 1 to 2 months, and 6 to 18 months of age (figure 3A); the optimal intervals and need for hepatitis B immune globulin (HBIG) are determined by the mother's hepatitis B surface antigen (HBsAg) status and the infant's gestational age and birth weight (algorithm 1 and algorithm 2 and table 2A-B). HepB immunization schedules for other countries are available through the World Health Organization. (See 'Routine infant immunization' above.)

Infants born to HBsAg-positive mothers and infants born to women whose HBsAg status remains unknown indefinitely should have postvaccination serology (both HBsAg and antibody to HBsAg) after receiving ≥3 doses of HepB vaccine, usually at 9 to 12 months of age (algorithm 1 and table 7). (See 'HBsAg-positive mother or mother with other evidence of HBV infection' above and 'Postvaccination serology' above.)

Catch-up immunization – In the United States, catch-up HepB immunization is indicated for all children and adolescents <19 years of age (table 4) (see 'Catch-up immunization' above):

Who are unvaccinated or incompletely vaccinated against hepatitis B virus

Whose HepB immunization status is unknown or uncertain

Who received doses of HepB vaccine that were administered inappropriately

Vaccine administration – The dose of HepB vaccine varies with the recipient's age and whether the recipient is receiving hemodialysis or is immune compromised (table 1). HepB vaccine is administered intramuscularly, usually in the anterolateral thigh for children <3 years and the deltoid for children ≥3 years (table 3). Different limbs should be used if HepB vaccine and HBIG are administered at the same time (ie, same day, same clinic visit). The injections may be administered in any order. (See 'Vaccine administration' above.)

Contraindications and precautions – Contraindications to HepB vaccine include hypersensitivity to yeast or to any vaccine component (table 6). (See 'Contraindications and precautions' above.)

Adverse reactions – HepB vaccines are safe; the most frequently reported side effects are pain at the injection site and low-grade fever. (See 'Adverse reactions' above.)

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Topic 101483 Version 58.0

References

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