Discussion

Epidemiology of Hepatitis B in the United States

The overall incidence of acute hepatitis B in the United States fell by 82% from 1990 to 2007 in conjunction with the widespread use of the hepatitis B vaccine (Figure 1). In 2007, approximately 4,500 cases of symptomatic acute HBV were reported in the U.S., but when taking into account asymptomatic infection and underreporting, the Centers for Disease Control and Prevention (CDC) estimated that 43,000 new hepatitis B infections occurred in 2007[1]. Hepatitis B infection rates vary by age, with the highest rates (2.9 cases per 100,000 population) occurring in persons 25-44 years old (Figure 2) . Sexual contact has become the predominant mode of transmission for hepatitis B in the United States. Among persons with acute hepatitis B infection in 2007 who reported risk factors for acquiring hepatitis B, 38% had more than one sex partner in the 6 months prior to illness , 15% had injection drug use, 12% surgery, and 11% had male-male sexual contact [1]. Thus, identifying and vaccinating adults at risk for hepatitis B plays a key role in reducing new hepatitis B infections in the U.S.

Delivery of Vaccination Services

Although acceptance of vaccine is high among adults offered hepatitis B vaccination[2], adult vaccine delivery and coverage is often low[3,4]. In a recent national survey of physician practices for hepatitis B vaccination, only 31% of primary care physicians reported routinely assessing for and vaccinating adults who reported risk factors for hepatitis B infection[4]. Among men who have sex with men surveyed in the Young Men's Health Study, only 17% had received hepatitis B vaccine, despite more than 90% of those susceptible to hepatitis B having reported regular health care systems, which included testing for HIV or receiving treatment for a sexually transmitted disease[3]. The low rate of HBV immunization in these instances represents missed opportunities to provide vaccination to adults at high risk of acquiring hepatitis B.

Indications for Hepatitis B Vaccination in Adults

The Advisory Committe on Immunization Practices (ACIP) has issued recommendations for hepatitis B vaccination in adults (Figure 3 and Figure 4), with indications based on (1) known risks for acquisition of hepatitis B infection, (2) populations where hepatitis B infection would have significant health impact, including persons with chronic liver disease or HIV infection, and (3) certain health care evaluation or treatment settings (where a high proportion of clients have known risk factors for hepatitis B infection).

Administration and Dosing of Hepatitis B Vaccine

Two single antigen vaccines (Engerix-B and Recombivax HB) and one combination antigen vaccine (Twinrix, combined hepatitis A and B) are currently license for adults in the United States. All vaccines use HBsAg as the antigen in the vaccine. In the U.S., recombinant DNA technology is used to generate HBsAg for all hepatitis B vaccines and the vaccines do not contain thimerosal (or contain only trace amounts from the manufacturing process). The recommended schedules and dosing for hepatitis B vaccination are shown in Figure 5 and Figure 6. Key points are outlined below:

  • Hepatitis B vaccine should be administered intramuscularly (22-25 gauge, using a one to one and a half inch needle) in the deltoid muscle. The vaccine should NOT be administered in the buttock, as administration by this route is associated with lower levels of protective immune response, likely due to failure to reach an intramuscular site for injection[6,7].
  • Anyone who has had a serious allergic response to a prior dose of hepatitis B vaccine, a component of the hepatitis B vaccine, or yeast should not receive hepatitis B vaccine.
  • A hepatitis B vaccination series started with vaccine from one manufacturer may be continued with vaccine from another manufacturer, as vaccines made by different manufacturers are considered interchangeable for adult immunization schedules[5].
  • The combined hepatitis A-hepatitis B vaccine (Twinrix) contains a lower quantity of hepatitis A vaccine per dose than dose the standard single antigen hepatitis A vaccine, thus allowing the administration of three doses of the combined vaccine instead of the usual two doses for the single-antigen hepatitis A vaccine.
  • Some departure from the standard schedule of months 0, 1 and 6 may not impact immunogenicity. Differences in vaccine response have not been observed as long as the minimum interval of time between the 3 doses of hepatitis B vaccine is achieved: 4 weeks between doses 1 and 2, 8 weeks between doses 2 and 3, and 16 weeks between doses 1 and 3[5].

Response to Vaccine

A full series of vaccine is desirable, although 32 to 56% of persons achieve protective levels of anti-hepatitis B surface antibody (HBsAb) with a single dose of vaccine, a percentage that rises to 70 to 75% with two doses. A third dose generates a protective response in more than 90% of healthy vaccinees and provides long lasting protection[8,9]. Certain conditions are associated with decreased response to vaccine including age greater than 40 years, male sex, genetic factors, obesity, tobacco smoking, alcoholism, renal disease, HIV infection, and other immune compromising conditions[6,10,11,12,13,14,15,16,17]. After completion of a vaccine series, a HBsAb level >=10 mIU/mL is considered protective. In general, protection generated by a complete vaccine series is believed to last for at least 15 to 20 years in healthy individuals. Immunity in healthy adults and children appears to persist even though antibody levels may decline over time to low levels, even below detectable limits[18,19,20,21,22,23].

Approach to Vaccine Non-Responders

Approximately 5-10% of immunized individuals fail to develop a protective antibody response to hepatitis B vaccination; genetic predisposition and impaired lymphocyte activation have been implicated in poor response. For persons who fail to generate adequate antibody levels in response to a primary three-dose vaccine series (HBsAb level <10 mIU/mL), a fourth dose of vaccine or a second full 3-dose revaccination series can achieve a protective response in half or more of these persons[24,25,26,27,28]. Non-responders to a second vaccine series are unlikely to develop a protective response to further doses of vaccine[29].

Hepatitis B Vaccination for Special Populations

Larger doses or additional doses of vaccine may be required in certain populations known to have a diminished response to vaccination. For hemodialysis patients, either a 3-dose or 4-dose vaccine series, using an increased dose of vaccine, is recommended (Figure 5). These regimens may also be considered for use in other immunocompromised persons (HIV-infected individuals, transplant recipients, etc.), but data evaluating response to these alternative vaccine doses and schedules are limited[16,30,31].

Post-Vaccination Testing

Post-vaccination testing for levels of HBsAb is not routinely recommended for adults. In contrast, post-vaccination serologic testing should be considered for persons who have known ongoing risk for hepatitis B exposure, known diminished protective response to vaccine, or whose clinical management depends on knowledge of their hepatitis B immune status. These persons generally belong to one of the following three groups: (1) sex partners of persons with chronic hepatitis B infection, (2) health care workers and public safety workers at risk for continued exposure to blood and body fluids, and (3) immunocompromised persons, including individuals with chronic renal disease, hemodialysis patients, and HIV-infected persons. If indicated, post-vaccination testing should be done 1-2 months after completion of the vaccine series. A HBsAb level of >=10 mIU/mL is considered protective[5,32].

Pre-vaccination Serologic Testing

Pre-vaccination serologic testing has two potential roles. The first is to identify those persons with existing immunity to hepatitis B and do not require vaccination. In general, this approach has not been recommended in routine settings, where background immunity to hepatitis B is low, because it is not cost-effective. Studies suggest that pre-vaccination serologic screening only becomes cost-effective if levels of pre-existing immunity exceed 20 to 30% in the population being vaccinated[33,34,35]. Of note, vaccination of persons who are already immune to hepatitis B or chronically infected with hepatitis B does not increase the risk for adverse events associated with vaccination. The second role for pre-vaccination screening is to detect persons with chronic active hepatitis B. Identifying these persons offers the opportunity for medical evaluation and treatment of HBV-infected individuals. It also presents the opportunity to interrupt ongoing transmission of hepatitis B to susceptible household contacts and sex partners by providing them with counseling, postexposure prophylaxis, and vaccination[36].

Pre-vaccination serologic testing should not be a barrier to vaccination of potentially susceptible persons, especially in populations that are difficult to access or engage in regular health care. The first dose of vaccine can be delivered at the time blood is collected for serologic testing. In venues where vaccination is recommended and serologic testing is not feasible, vaccination should still be provided for those in whom vaccination is recommended[5,36]. Adult populations currently recommended for pre-vaccination serologic screening for hepatitis B include the following[5,36]:

  • All foreign born persons (including immigrants, refugees, asylum seekers, and internationally adopted children) born in Africa, Asia, the Pacific Islands, and other regions with high endemicity of hepatitis B infection (HBsAg prevalence of >= 8%) (Figure 7).
  • Household, sex, and needle sharing contacts of HBsAg-positive persons
  • Consider pre-vaccine screening in adult populations with a prevalence of HBV infection (including previous or chronic infection) that exceeds 20%, such as in injection drug users, men who have sex with men, and persons from areas of intermediate to high endemicity for hepatitis B (Figure 7).
  • Other populations where identification of active hepatitis B infection could impact individual health or transmission to others: pregnant women, hemodialysis patients, HIV-infected persons, persons known or suspected of having been exposed to hepatitis B.

Booster Doses

Booster doses of hepatitis B vaccine are not recommended for healthy persons who were vaccinated as children, adolescents, or adults. Due to potential waning of protective immunity over time and the possibility of continued exposure to hepatitis B, hemodialysis patients should receive yearly testing for HBsAb levels with administration of a booster dose of hepatitis B vaccine when HBsAb levels fall below 10 mIU/mL. For other immunocompromised persons, the need for booster doses has not been determined, but may be considered in those who have an ongoing risk of exposure to hepatitis B using a strategy similar to that in hemodialysis patients.

Other Resources on Hepatitis B Vaccination

Additional information on frequently asked questions regarding hepatitis B vaccine can be found at: www.cdc.gov/hepatitis/HBV/HBVfaq.htm (Hepatitis B FAQs for Health Professionals).

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    Figure 1 - Incidence of Acute Hepatitis B Virus Infection in the United States, 1990-1997

    From: Daniels D, Grytdal S, Wasley A; Centers for Disease Control and Prevention (CDC). Surveillance for Acute Viral Hepatitis—United States, 2007. MMWR Surveill Summ. 2009;58:1-27.

    Figure 1
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    Figure 2 - Image 1. Incidence* of Acute Hepatitis B in Females, by Age Group, in U.S., 2007

    From: Daniels D, Grytdal S, Wasley A; Centers for Disease Control and Prevention (CDC). Surveillance for Acute Viral Hepatitis—United States, 2007. MMWR Surveill Summ. 2009;58:1-27.

    Figure 2

    From: Daniels D, Grytdal S, Wasley A; Centers for Disease Control and Prevention (CDC). Surveillance for Acute Viral Hepatitis—United States, 2007. MMWR Surveill Summ. 2009;58:1-27.

    From: Daniels D, Grytdal S, Wasley A; Centers for Disease Control and Prevention (CDC). Surveillance for Acute Viral Hepatitis—United States, 2007. MMWR Surveill Summ. 2009;58:1-27.

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    Figure 3 - Adults Recommended to Receive HBV Vaccine

    From: Mast EE, Weinbaum CM, Fiore AE, et al. 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 Recomm Rep. 2006;55(RR-16):1-33.

    Figure 3
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    Figure 4 - Settings in which Hepatitis B Vaccination is Recommended.

    From: Mast EE, Weinbaum CM, Fiore AE, et al. 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 Recomm Rep. 2006;55(RR-16):1-33.

    Figure 4
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    Figure 5 - Recommended Doses of Hepatitis B Vaccination in Adolescents and Adults

    From: Source: CDC FAQs for Health Professionals. www.cdc.gov/hepatitis/HBV/HBVfaq.htm

    This figure is adapted from Updated U.S. Public Health Service guidelines for the management of occupational exposures to HBV, HCV and HIV and recommendations for postexposure prophylaxis. MMWR Morb Mortal Wkly Rep 2001; 50(RR-11): 1-52.

    Figure 5
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    Figure 6 - Hepatitis B Vaccine Schedules for Adults 20 Years of Age.

    Adapted from: Mast EE, Weinbaum CM, Fiore AE, et al. 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 Recomm Rep. 2006;55(RR-16):1-33.

    Figure 6
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    Figure 76 - Prevalence of Chronic HBV Infection, Worldwide, 2006

    For Multiple countries, estimates of prevalence of hepatitis B surface Ag (HBsAg), a marker of chronic infection are based on limited data and might not reflect current prevalence in countries that have implemented childhood hepatitis B vaccination. In addition, HBsAg prevalence might vary by subpopulation and locality.

    From: Weinbaum CM, Williams I, Mast EE, et al. Recommendations for identification and public health management of persons with chronic hepatitis B virus infection. MMWR Recomm Rep. 2008;57(RR-8):1-20.

    Figure 7