Vaccines: Hepatitis B

Specific vaccination recommendations vary among countries or even within a given country. Local or country-specific guidelines should be consulted.

1. Vaccines: All hepatitis B vaccines available in North America contain recombinant hepatitis B surface antigen (HBsAg). Many formulations are available, including monovalent hepatitis B vaccines; combination hepatitis A/B vaccines; and a combination vaccine containing recombinant hepatitis B, inactivated poliomyelitis virus, acellular pertussis, conjugated Haemophilus influenzae type b, and diphtheria and tetanus toxoids (DTaP-HB-IPV-Hib). Hepatitis B immunoglobulin (HBIG) is derived from pooled human plasma.

2. Indications: Hepatitis B virus (HBV) vaccination is recommended as part of the primary childhood vaccination series for all children in North America and additionally in the following high-risk groups:

1) Persons with lifestyle risk factors, such as IV drug use, history of sexually transmitted infections, >1 sexual partner in the past 6 months, engaging in unprotected sexual intercourse with new partner(s), and men who have sex with men (MSM).

2) Persons with congenital immunodeficiencies and those with acquired immunodeficiency, such as in HIV infection, hematopoietic stem cell transplant recipients, and solid organ transplant recipients.

3) Persons with occupational exposure to blood, such as health care workers, and patients with conditions that require blood product transfusions.

4) Household and sexual contacts of patients with acute HBV infection.

5) Patients born in endemic areas, children born to parents who immigrated from endemic areas, household contacts of adopted children from endemic regions that are HBsAg-positive, and travelers to endemic regions.

6) Patients with chronic liver disease from any cause and patients with chronic kidney disease, including those on peritoneal dialysis or hemodialysis.

7) Patients at risk of HBV infection due to close contact with patients with HBV infection (eg, household contacts of patients with hepatitis B, residents of nursing homes, inmates of correctional facilities).

3. Contraindications include general contraindications for all inactivated vaccines. Pregnancy and breastfeeding are not contraindications to hepatitis B vaccination. In the rare instance that patients have yeast hypersensitivity, the decision to vaccinate should be made in conjunction with an allergist, as recombinant HBV vaccines use yeast proteins in their development.

4. Serologic testing prior to vaccination is recommended in all pregnant patients (HBsAg) and in high-risk patients with a potential percutaneous or mucosal exposure to HBV (HBsAg or anti-HBs IgG). Such high-risk patients should be offered vaccination if there is no evidence of immunity or current HBV infection.

5. Immunization schedules:

1) The primary vaccination series in childhood typically uses the combination DTaP-HB-IPV-Hib vaccine, with 3 doses administered IM in the deltoid muscle at 2, 4, and 6 months of age, or at 2, 4, and 12 to 24 months of age. In exceptional cases of patients with significant thrombocytopenia or coagulopathy, the vaccine can be administered subcutaneously, but this is associated with weaker immune responses. In patients who have completed the primary vaccination series (except for some patients with chronic diseases; see below), booster doses are not recommended even if anti-HBs IgG levels fall below the protective level (10 IU/L) several years after the primary vaccination.

2) The accelerated vaccination schedule can be used in adults in exceptional cases when rapid immunization is necessary, such as prior to travel to endemic areas. Use a vaccine that is approved for accelerated immunization schedules and follow the manufacturer’s instructions. The schedule includes 4 doses of the vaccine on days 0, 7, 21, and at 12 months (protective antibody levels are found in 75%-83% of vaccinated persons 1 month after the third dose and in 90%-97% of vaccinated persons 2 months after the third dose; the percentages are slightly higher in patients receiving a combined hepatitis A and hepatitis B vaccine).

3) In immunocompromised patients and those with chronic renal or hepatic dysfunction, seroconversion to an appropriate antibody titer (≥10 IU/L) is typically inadequate or transient. In such cases, and only where recommended by the manufacturer of the vaccine used in your jurisdiction, a double dose of the vaccine (40 microg) should be administered; in the case of some vaccine formulations, another dose should be added to the primary vaccination schedule (eg, at 0, 1, 2, and 6 months). Measure serum anti-HBs levels 1 to 2 months after the administration of the last dose. Patients with antibody levels <10 IU/L should be managed as nonresponders (see below). Serum anti–HBs levels should be monitored in these patients (see below) every 6 to 12 months.

4) In nonresponders to primary vaccination (anti­-HBs IgG <10 IU/L 1-2 months after a completed primary vaccination series, observed in ~10% of adults; risk factors include male sex, age >40, obesity, smoking, chronic kidney disease, chronic liver disease, alcohol dependence, immunosuppression, HIV infection), repeat the entire primary series (protective serum antibody levels are achieved in 50%-70% of patients). Measure serum anti–HBs levels 1 to 2 months after the repeated vaccination series; patients with anti-HBs levels <10 IU/L are classified as permanent nonresponders. In the case of HBV exposure in such patients, use HBIG (see below).

6. Postexposure prophylaxis: see Table 1 in Occupational Exposures to Blood-Borne Viral Infections.

7. Postvaccination serologic testing: Within 1 to 6 months of completion of the HBV vaccination series, the following high-risk groups should have an anti-HBs IgG titer measured to confirm antibody levels ≥10 IU/L: immunocompromised patients, those with chronic hepatic or renal disease, solid organ transplant recipients, pregnant patients (if high-risk), and sexual or household contacts of HBV-infected patients. Infants born to HBV-infected mothers should have serologic testing done no sooner than 1 to 4 months after the completion of HBV vaccination and no earlier than 9 months of age. Ongoing annual monitoring of anti-HBs titers is recommended in the immunocompromised as long as risk of HBV infection persists and in those with chronic renal disease or on dialysis; if the anti-HBs IgG titer is <10 IU/L in these patients, a booster dose may be warranted.

8. HBIG is indicated to prevent infection in case of HBV exposure in susceptible unvaccinated individuals or nonresponders. In infants born to HBsAg-positive mothers, a 0.5 mL IM dose of HBIG should be administered along with a single dose of monovalent HBV vaccine within 12 hours post partum. In older children and adults, where indicated, 0.06 mL/kg HBIG should be administered IM, preferably within 48 hours of exposure.

9. Adverse events: Transient local reactions at the injection site, headache, and fever (in 10% of individuals). With HBIG, urticaria, angioedema, and diarrhea may also occur. Case reports of chronic fatigue syndrome, Guillain-Barré syndrome, or multiple sclerosis following administration of the vaccine have been described, but no causal link has been demonstrated in the scientific literature.