Hepatitis A and B rate falls as vaccination efforts increase

July 2005

Hepatitis A virus (HAV) and hepatitis B virus (HBV) are among the most prevalent vaccine-preventable diseases.

Vaccines against these infections have been commercially available in the United States since 1981 for HBV and 1995 for HAV. While both hepatitis A and B infections occur throughout the world, HBV infections are endemic in Africa, eastern Europe, the Middle East, Central and Southeast Asia, China, the Pacific Islands and the Amazon basin of South America. In these areas, as many as 70% of the adult population test positive for prior HBV infections and up to 15% are chronic carriers of the virus. The CDC estimates that up to one-third of Americans have evidence of a past hepatitis A infection and that nearly 73,000 Americans became infected with hepatitis B in 2003. Incidences of both hepatitis A and B infections have fallen dramatically over the past decade in the United States due to increased immunization efforts.

Hepatitis B

HBV is a double-stranded DNA virus that is highly infectious in individuals without immunity. Infection may occur from percutaneous or mucosal exposure to blood or bodily fluids from infected people. Infected individuals do not need to be symptomatic to transmit HBV. The most common sources of exposure are from sexual contact, contaminated blood or blood products, contaminated needles and perinatal exposure. Young adults between the ages of 18 and 39 are at the highest risk for HBV infection due to high-risk behaviors common in this age group. According to statistics from the CDC, about one-third or more of cases of acute HBV infection occur from an unidentified source of infection.

Once acutely infected with HBV, individuals may either clear the infection or it may exist as a chronic, indolent infection that can lead to hepatic cirrhosis, liver failure, hepatocellular carcinoma or death. HBV vaccination has been referred to as the first “cancer vaccine,” in that widespread immunizations against HBV have significantly reduced the occurrence of hepatocellular carcinoma. The CDC estimates that for every 1 million at-risk adults vaccinated for HBV, 150 to 450 deaths due to cirrhosis or hepatocellular carcinoma are prevented.

HBV vaccine is produced in yeast cells using recombinant techniques and is a noninfectious subunit viral vaccine containing hepatitis B surface antigen. Since 1991, the Advisory Committee on Immunization Practices (ACIP) has recommended universal HBV vaccination for infants. The first dose of the vaccine, often referred to as the “birth dose,” is recommended prior to infants’ departure from the hospital following birth. If not vaccinated at birth, ACIP recommends that all children up to age 18 be vaccinated because this age group is at the greatest risk for developing chronic hepatitis B if exposed to the virus.

Currently, universal HBV vaccination is not recommended for adults. As mandated by the Occupational Safety and Health Administration since 1991, all health care workers must be educated about HBV vaccination and offered it free of charge. The following groups are considered at risk for HBV infection by the CDC and should receive vaccination:

• Alaska Natives and Pacific Islanders
• Health care or public-safety workers who are exposed to blood
• Clients and staff of institutions for the developmentally disabled
• Hemodialysis patients
• Recipients of certain blood products, such as clotting-factor concentrates
• Household members and sexual partners of HBV carriers
• Adopted children from countries where HBV infection is endemic
• Travelers who plan to spend more than 6 months in an area where HBV infection is endemic or short-term travelers likely to have sexual contact or blood contact with residents in these areas
• People who have more than one sexual partner in 6 months
• People who have had a recent sexually transmitted disease
• Men who have sex with men
• Intravenous drug users and their sex partners
• Inmates of long-term correctional facilities

Table 1 lists the HBV vaccines currently available in the United States and recommended dosing. HBV vaccine should be administered intramuscularly in the thigh for neonates and infants and in the deltoid muscle for children, adolescents and adults. In most cases, the vaccine is a three-dose series although there is a two-dose series (adolescents 11-15 years of age) and a four-dose series schedule. Should there be prolonged intervals between doses, there is no need to restart the series. Vaccines from different manufacturers may be used interchangeably throughout the series.

The antibody response to HBV vaccination, as determined by the anti-HB antibody level, should be checked after the last dose in the vaccine series in individuals at high risk for exposure to blood or body fluids or those with risk factors for a lack of response. Patients at risk for a decreased response to the vaccine include obese patients, individuals older than age 30 or patients with underlying immunodeficiency. It is estimated that 90% of healthy adults and 95% of healthy children have protective levels of antibodies following HBV vaccination. Antibody response may wane with increasing age; however, there is no consensus on revaccination. In people who do not produce an adequate anti-HB antibody level following initial vaccination, a second series of three doses of the vaccine is recommended. With this, 50% to 60% of this group will develop adequate antibody responses. There are currently several new HBV vaccines in different clinical trial phases for poor or non-responders to the currently available formulations.

Hepatitis B immune globulin (HBIG) may be used in individuals without demonstrated immunity to HBV (never vaccinated, nonresponders to vaccine or unknown vaccination status) and patients who have been exposed to the virus. To prevent infection, HBIG should be administered within 24 hours following birth for perinatal exposure, within seven days of needle stick exposure and within 14 days following sexual exposure. If the individual has never received the HBV vaccine, it is recommended that they also start the vaccine series to prevent future infections if re-exposed. When administered closely following exposure, HBIG is 75% to 95% effective in prevention of infection.

Hepatitis A

HAV replicates in the liver, is transported through bile to the stool and is shed for several weeks following infection. HAV is passed from person-to-person through the fecal-oral route with the most frequent occurrence through the ingestion of contaminated food and drink. Epidemics occur both nationwide and in communities. While most adults with HAV infection are symptomatic, nearly 70% of children under age 6 are asymptomatic when infected with the virus. For this reason, young children are considered to be the primary source of transmission in the community. CDC surveillance programs estimate that greater than 50% of patients with HAV could not identify their source of infection.

Contrary to popular belief, outbreaks of HAV are rarely associated with restaurants. The most common risk factors for transmission include household or sexual contact with a person with HAV, recent IV drug use, attendance or employment at a day care center or recent travel to countries where HAV is endemic. While there is no chronic infection resulting from HAV, acute infection may result in coagulopathy, encephalopathy or renal failure. HAV vaccine and immune globulin (IG) are both used to prevent HAV infection.

ACIP recommends that HAV vaccination be offered to all people at least 2 years of age who are at high risk of infection. These groups include the following:

• People living in a state or county with a high rate of infection (>20 cases per 100,000 population from 1987 to 1997)
• People traveling to countries with high or intermediate rates of disease
• Household or sexual contacts of infected people
• Men who have sex with men
• Injecting and noninjecting drug users
• People with clotting-factor disorders such as hemophilia
• People with chronic liver disease
• Laboratory personnel who work with HAV

HAV vaccine preparations contain formalin-inactivated HAV. HAV vaccination is not approved for use in children younger than age 2 due to concerns that those who may have passively acquired maternal HAV antibody will have a poor response to the vaccine. The vaccine efficacy rate for HAV ranges from 94% to 100% in healthy adults. Poor responders include patients with chronic liver disease (93% response), immunocompromised people (88% response), transplant recipients (26% response) and the elderly (65% response). Although experience with HAV vaccination has been limited, it appears to provide long-term protection from infection.

HAV vaccines currently available in the United States are listed in Table 1. A two-dose series is recommended. If a longer time lapse between the doses occurs, there is no need to repeat the series. HAV vaccine should be administered in the deltoid muscle and can be given concurrently with other vaccines. HAV vaccination is FDA-approved for one month or more before international travel. However, studies have shown that antibody protection is present in most people two weeks following the first dose in the series. A combination vaccine against both HAV and HBV is available for people ages 17 or older (Table 1). This vaccine has been shown to be equally as efficacious as both vaccines given separately.

IG containing concentrated nonspecific antibodies from pooled human plasma may be given to people traveling to areas with a high rate of HAV disease within the next two weeks (and have not received the HAV vaccine in time to develop antibodies) or to children less than 2 years of age who will be traveling to such an area. IG is also used for postexposure prophylaxis of HAV transmission in those exposed to the virus within the past 14 days. When dosed at 0.02 ml/kg of body weight intramuscularly, IG has been shown to be more than 85% effective at prevention of HAV disease following close exposure to the virus.

Vaccine safety

Both the HBV and HAV vaccines are considered to be very safe and effective. While there have been concerns about potential vaccine-related autoimmune diseases such as chronic fatigue syndrome or demyelinating disorders with vaccines, there are no scientific data to support these concerns. All pediatric hepatitis vaccines are now manufactured without thimerosal, a mercury-based preservative previously used in the formulations.

HBV vaccine is contraindicated in people who have had a serious allergic reaction to baker’s yeast or to a previous dose of the HBV vaccine. HAV vaccine is contraindicated in people who have experienced a severe allergic reaction to a previous dose of HAV vaccine or those who have an allergy to alum or 2-phenoxyethanol, compounds which are present in some HAV vaccine preparations. Because the safety of HAV vaccine has not been established in pregnancy; pregnant women are usually not given the vaccine unless they are at high risk for exposure to HAV. It is generally recommended that people who are moderately to severely ill at the time a dose of the HBV or HAV vaccine is scheduled should wait until recovery before getting vaccinated. While the vaccine is generally well-tolerated, soreness at the injection site or a mild fever may occur for a few days following vaccination. In addition, HAV vaccine may cause mild, limited fatigue, headache or loss of appetite. Unexpected adverse reactions to any vaccine should be reported to the Vaccine Adverse Event Reporting System.

Ed note: I believe restaurant-associated outbreaks of HAV are mischaracterized by the authors, especially if one adds other food service workers to the equation. Foodborne hepatitis A outbreaks are (fortunately) infrequent, but not rare in my experience. One of the best-known hepatitis A outbreaks in the Denver area nearly wiped out a highly respected catering company after serving -contaminated items at a large Christmas party. — Theodore C. Eickhoff, MD

For more information:

• See the following Web sites:
• Advisory Committee on Immunization Practices: www.cdc.gov/nip/ACIP/default.htm
• Centers for Disease Control National Immunization Program: www.cdc.gov/nip/default.htm
• Hepatitis B Foundation: www.hepb.org
• ACIP Recommended Adult Immunization Schedule: www.cdc.gov/nip/recs/adult-schedule.htm
• ACIP Recommended Childhood Immunization Schedule: www.cdc.gov/nip/recs/child-schedule.htm
• CDC Guide to Contraindications to Vaccinations: www.cdc.gov/nip/recs/contraindications.htm
• Vaccine Adverse Event Reporting System: vaers.hhs.gov

• Stephanie B. Hollowell, PharmD, and Mary L. Townsend, PharmD, work with Campbell University School of Pharmacy and Durham VA Medical Center, Pharmacy Department.