Aetna considers hepatitis B vaccine a medically necessary preventive service for members with any of the following indications:

1. Infants, regardless of hepatitis B surface antigen (HBsAg) status of the mother; or

2. Children and adolescents (0-18 years) who have not been vaccinated previously; or

3. Adults (over 18 years of age) at increased risk for hepatitis B infection, including:

   • hemophiliacs
   • injecting-drug users
   • persons with a history of multiple sex partners
   • persons with a recent sexually transmitted disease
   • men who have sex with men
   • international travelers to geographic areas of high endemicity*
   • household and sexual contacts of hepatitis B virus carriers
   • persons who undergo hemodialysis
   • health-care workers*
   • inmates of long-term correctional facilities*
   • hepatitis C virus positive persons, or
   • persons with chronic liver disease.

4. Transplant candidates of any age.

Aetna considers hepatitis B vaccine experimental and investigational for all other indications.

*Note: Aetna generally does not cover immunizations required for travel or because of work-related risk. Check contract language, limitations and exclusions for coverage details.

Pre-exposure immunization of susceptible persons with hepatitis B vaccine is the most effective means to prevent hepatitis B virus (HBV) transmission. To reduce transmission of HBV and eventually to eliminate it, universal immunization is necessary. Vaccination against HBV has been recommended as part of routine early childhood immunizations since 1991. Accordingly, immunization of all children before or during adolescence is necessary and recommended. Along with universal immunization efforts, immunization of adults belonging to identified high-risk groups is appropriate. Post-exposure evaluation and treatment, including diagnostic testing and immunization in selected cases, is also appropriate to prevent HBV infection among individuals of all ages regardless of the presence or absence of risk factors.

These indications blend the recommendations of the Advisory Committee on Immunization Practices (ACIP), the American Academy of Pediatrics (AAP), and the American Academy of Family Physicians (AAFP). These three groups, working with federal agencies, have approved a unified childhood immunization schedule. The recommendations for hepatitis B vaccine in the unified schedule are generally similar to those recommended by the U.S. Preventive Services Task Force (USPSTF). However, routine hepatitis B vaccine was recommended only in infancy in the unified schedule, whereas the USPSTF also recommends its routine use in all children and adolescents not previously immunized. The ACIP and AAP have subsequently revised their recommendations for hepatitis B vaccine to include all children aged 11-12 years who have not previously been vaccinated; ACIP also recommends vaccinating unimmunized children under 11 years who are Pacific Islanders or who reside in households of first-generation immigrants from countries with high or intermediate HBV endemicity.

Three doses of hepatitis B vaccine are required for complete immunization. For infants, the Centers for Disease Control and Prevention (CDC) and the Advisory Committee on Immunization Practices (ACIP) recommend hepatitis B vaccine be incorporated into the routine vaccination schedules for children.

Hepatitis B vaccine has been administered using an accelerated immunization protocol for persons who are candidates for solid organ, bone marrow or stem cell transplantation to reduce the risk of hepatitis infection from administration of blood products and transplanted organs.

The annual recommended childhood and adolescent immunization schedule for January-December 2006 approved by the American Academy of Pediatrics, the Advisory Committee on Immunization Practices of the Centers for Disease Control and Prevention, and the American Academy of Family Physicians (2006) states that vaccination of infants born to HBsAg-negative mothers can be delayed in rare circumstances, but only if a physician's order to withhold the vaccine and a copy of the mother's original HBsAg-negative laboratory report are documented in the infant's medical record. Administering 4 doses of HepB is permissible (e.g., when combination vaccines are administered after the birth dose); however, if monovalent HepB is used, a dose at age 4 months is not needed. For infants born to HBsAg-positive mothers, testing for HBsAg and antibody to HBsAg after completion of the vaccine series should be conducted at age 9 to18 months (generally at the next well-child visit after completion of the vaccine series).

In a randomized, controlled study, Cornejo-Juárez et al (2006) found that an increase dose of HBV vaccine did not increase the rate of response in HIV infected subjects. These researchers assessed 2 doses of recombinant HBV vaccine (10 or 40 microg), IM at 0, 1 and 6 months. Vaccination response was measured 30 to 50 days after last dose; titers of greater than 9.9 IU/L were considered positive. A total of 79 patients were included, 48 patients (60.7 %) sero-converted. Thirty-nine patients (49.3 %) received 10 microg vaccine dose, 24 patients (61.5 %) sero-converted. Forty patients (50.7 %) received 40 microg vaccine dose, 24 (60 %) sero-converted. There were no differences between the two doses. A statistically significant higher sero-conversion rate was found for patients with CD4 cell counts at vaccination greater than or equal to 200 cell/mm3 (33 of 38 patients, 86.8 %), compared with those with CD4 less than 200 cell/mm3 (15 of 41, 36.6 %), [OR 11.44, 95 % IC 3.67 - 35.59, p = 0.003], there were no differences between two vaccine doses. Using the logistic regression model, CD4 count less than 200 200 cell/mm3 were significantly associated with non serological response (p = 0.003). None other variables such as gender, age, risk exposure for HIV, viral load, type or duration of highly active anti-retroviral therapy or AIDS-defining illness, were associated with sero-conversion. The authors concluded that an increase dose of HBV vaccine did not show to increase the rate of response in HIV infected subjects. The only significant findings associated to the response rate was that a CD4 count greater than or equal to 200 cell/mm3, these investigators suggested this threshold at which HIV patients should be vaccinated.

Pasricha and colleagues (2006) evaluated the effectiveness of recombinant vaccine in treatment-naive HIV-positive patients and healthy controls, and ascertained differences if any, in different limbs of immune response. A total of 40 HIV-positive patients and 20 HIV-negative controls, negative for HBsAg, HBsAbs and HBcAbs were vaccinated with three doses of 40 microg and 20 microg of vaccine, respectively. Patients were divided into high-CD4 and low-CD4 group based on CD4+ lymphocytes of 200 and less than 200/mm3, respectively. Group II consisted of healthy controls. Detection of phenotypic markers was done by flow cytometry. Cytokine estimation was done by sandwich ELISA. HBsAbs were estimated in serum by ELISA. After vaccination, CD4+, CD8+ and CD3+ cells increased significantly in all the groups. There was no increase in NK cell activity in patients with high CD4+ lymphocytes and only a marginal increase in patients with low CD4+ lymphocytes (170 to 293/mm3) whereas a marked increase was observed in controls (252 to 490/mm3). After vaccination, although an increase in memory cells was observed in HIV-positive patients, yet HBsAb levels were significantly lower than controls (p < 0.05) indicating a functional defect of memory cells in HIV/AIDS patients. Basal interferon-gamma levels were also significantly lower in HIV/AIDS patients (p < 0.01). Although the levels increased after vaccination, the peak level remained lower than in controls. HBsAb titers were much lower in HIV-positive patients compared to controls. (high-CD4+ group: 8834 mIU/ml, low-CD4+ group: 462 mIU/ml versus controls: 16,906 mIU/ml). IL-4 and IL-10 were low in patients. The authors concluded that despite a double dose in patients, IL-4 and IL-10, which regulate antibody response, were also lower in patients, and this together with low CD4+ counts and lack of T help, accounted for low HBsAb levels. Vaccination in patients with CD4+ lymphocytes less than 50/mm3 was ineffective.

It is also interesting to note that extended double-dosage HBV vaccination (two cycles of three intramuscular double doses [40 microg], given at month 0, 1, 2, and 3, 4, 5) after liver transplantation is ineffective (Di Paolo et al, 2006).

In a Cochrane review on hepatitis B immunization in persons not previously exposed to hepatitis B or with unknown exposure status, Mathew and colleagues (2008) concluded that in people not previously exposed to hepatitis B, vaccination has unclear effect on the risk of developing infection, as compared to no vaccination. The risk of lacking protective antibody levels as well as serious and non-serious adverse events appear comparable among recipients and non-recipients of hepatitis B vaccine.