Hepatitis B: Preventive and Exposure Management
Donald M. Grubb MSN, ARNP

Introduction
Hepatitis B is a disease caused by the Hepatitis B virus (HBV) which is transmitted via percutaneous or mucosal exposure to infectious blood or body fluids. HBV can cause chronic infection resulting in cirrhosis of the liver and liver cancer, liver failure and death. Hepatitis B vaccination is the most effective measure to prevent Hepatitis B infection and its consequence. Since recommendations for Hepatitis B vaccination were first issued in 1982, a comprehensive strategy to eliminate HBV transmission has evolved. (1)

Clinical Features and Natural History of HBV Infection
HBV is a 42 anti-DNA virus classified in the Hepadnaviridae family. The liver is the primary site of HBV replication. After a susceptible person is exposed, the virus is delivered via the blood stream; no evidence exists indicating that the virus replicates on mucosal surfaces. HBV infection can produce asymptomatic or symptomatic infections. The average incubation period is 90 days (range: 60 to 150 days) from exposure to the onset of jaundice and 60 days (range: 40 to 90 days) from exposure to onset of abnormal serum alanine aminotransferase (ALT) levels.

HBV is transmitted by percutaneous or mucosal exposure to infectious blood or body fluids. Although Hepatitis B surface antigen has been detected in multiple body fluids, only serum, semen and saliva have been demonstrated to be infectious. HBV is concentrated most highly in serum, with lowest concentrations in semen and saliva. All Hepatitis B surface antigen positive persons are infectious; however those who are also Hepatitis B core antigen positive are more infectious because their blood contains high titers of HBV. HBV is comparatively stable in the environment and remains viable for greater than or equal to 7 days on environmental surfaces at room temperature. HBV DNA can be present on environmental surfaces in the absence of any visible blood and still cause transmission.

Prophylaxis against HBV Infection
Hepatitis B vaccine is available as a single - antigen formulation and also in fixed combination with other vaccines. Two single antigen vaccines are available in the US: Recombivax HB and Engerix-B. Hepatitis B vaccine is also available in a combination formula that provides vaccination against both Hepatitis A and B. Of the three licensed combination vaccines, one (Twinrix) is used for vaccination of adults. Hepatitis B surface antigen is the antigen used for Hepatitis B vaccination. Initially, vaccine antigen was purified from the plasma of persons with chronic HBV infection. Current vaccines are produced by recombinant DNA technology. Recombinant DNA technology is used to express Hepatitis B surface antigen in yeast, which is then purified from the cells by biochemical and biophysical separation. Hepatitis B vaccines produced for distribution in the US does not contain thimerosal as a preservative.

In people who have been exposed to a confirmed positive Hepatitis B source, Hepatitis B Immune Globulin (HBIG) typically is used as an adjunct to Hepatitis B vaccine for post exposure prophylaxis to prevent HBV infection. HBIG provides passively acquired antibodies to Hepatitis B surface antigen (Anti-HBs) and temporary protection (3-6 months) when administered in standard doses. For non-responders to the Hepatitis B vaccination, HBIG administered alone is the primary means of protection after HBV exposure. HBIG is prepared from plasma donors with high concentration of antibodies to Hepatitis B surface antigen. The plasma is screened to eliminate donors, who were positive for Hepatitis B surface antigen, antibodies to HIV and Hepatitis C virus (HCV). No evidence exists to indicate that HBV, HCV or HIV ever has been transmitted by HBIG commercially available in the United States. HBIG that is commercially available in the United States does not contain thimerosal.

Adult Vaccination Schedules
Primary vaccination consists of greater than or equal to three intramuscular doses of Hepatitis B vaccine. The three dose vaccine series administered intramuscularly at 0, 1 and 6 months produces a protective antibody response in approximately 30 to 50% of healthy adults age less than or equal to 40 years after the first dose; 75% after the second dose; and greater than 90% after the third dose. After age 40 years, the proportion of persons who have a protective antibody response after the 3 dose vaccination regimen declines below 90%, and by age 60 years, protective levels of antibodies developed in only 75% of vaccinated persons. In addition to age, other host factors (smoking, obesity, genetic factors and immune suppression) contribute to decreased vaccine response. Alternative vaccination schedules have been demonstrated to elicit dose specific and final rates of seroprotection similar to those obtained on 0, 1 and 6-month schedule.

Immune Memory
Anti- HBs (surface antibodies to Hepatitis B) is the only easily measurable correlate of vaccine induced protection. Immunocompetent persons who achieve antibody titers greater than or equal to 10 mlIU/mL after pre-exposure vaccination had nearly complete protection against both acute disease and chronic infection, even as anti-HBs concentrations declined subsequently to less than 10 units. After primary immunization with Hepatitis B vaccine, anti-HBs levels decline rapidly within the first year and more slowly thereafter. Among young adults who respond to a primary vaccine series with antibody concentrations greater than 10mlIU/mL, 50% have low or undetectable concentrations of antibodies 15 years after vaccination. Even when anti-HBs concentrations declined to less than 10IU, nearly all vaccinated persons remained protected against HBV infection. The mechanism for continued vaccine induced protection is thought to be the preservation of immune memory through B and T lymphocytes.

Post-Exposure Prophylaxis
Both passive and active post-exposure prophylaxis (PEP) using HBIG and Hepatitis B vaccine, as well as active PEP using Hepatitis B vaccine alone, are highly effective in preventing infection after exposure to HBV. HBIG alone has been demonstrated to be effective in preventing HBV transmission but, with the availability of Hepatitis B vaccine, HBIG typically is used as an adjunct to vaccination. Guidelines for PEP for adults with occupational and non-occupational exposures to HBV have been developed by the Centers for Disease Control (CDC).

The major determinant of the effectiveness of PEP is early administration of the initial dose of vaccine. The effectiveness of PEP diminishes the longer after exposure it is initiated. Studies are limited on the maximum interval after exposure during which PEP is effective, however the interval is likely less than 7 days for needle stick exposures and less than 14 days for sexual exposures.

Substantial evidence suggests that adults who respond to Hepatitis B vaccination are protected from chronic HBV infection for at least 20 years, even if vaccinees lack detectable antibodies to Hepatitis B at time of exposure. For this reason, immunocompetent persons who have had post vaccination testing and are known to have responded to Hepatitis B vaccine with antibody titers greater than 10 mIU/mL, do not require additional passive or active immunization after HB exposure and do not need further periodic testing to assess Hepatitis B antibody concentrations.

Conclusion
Hepatitis B vaccination is safe with minimal adverse side effects, most commonly pain at the injection site. Hepatitis B vaccination can eliminate disease and significantly affect morbidity and mortality from infection with Hepatitis B.

References
1. http://www.cdc.gov/mmwr/preview/mmwrhtml/rr5516a1.htm?s_cid=rr5516a1_e
2. http://www.cdc.gov/mmwR/PDF/rr/rr5516.pdf

Special thanks is given to the CDC staff for allowing me to summarize the MMWR Recommendation and Reports article titled “A Comprehensive immunization strategy to eliminate transmission of Hepatitis B virus infection in the United States“ December 8, 2006/vol 55/ No R R. – 16.

Donald Grubb received a Masters Degree in Nursing at the University of Virginia in Charlottesville. He is a certified Family Nurse Practitioner. He started his career in emergency nursing and currently holds over 20 years experience in the specialty of occupational health. He is a member of AAOHN and ACOEM. Don is a full-time NP at Lakeside Occupational Medical Centers at the Largo clinic.

For additional resources, visit www.lakesideoccmed.com