Hepatitis B Virus (HBV) Infection
The incubation period for HBV infection from time of exposure to symptom onset ranges from 6 weeks to 6 months. The highest concentrations of HBV are located in blood, with lower concentrations in other body fluids including wound exudates, semen, vaginal secretions, and saliva (1309,1310). HBV is more infectious and more stable in the environment than other bloodborne pathogens (e.g., HCV or HIV).
HBV infection can be either self-limited or chronic. Among adults, approximately half of newly acquired HBV infections are symptomatic, and approximately 1% of reported cases result in acute liver failure and death (1311). Risk for chronic infection is inversely related to age at acquisition; approximately 90% of infected infants and 30% of infected children aged <5 years become chronically infected, compared with 2%–6% of persons who become infected as adults (1312). Among persons with chronic HBV infection, the risk for premature death from cirrhosis or hepatocellular carcinoma is 15%–25% (1313).
HBV is efficiently transmitted by percutaneous or mucous membrane exposure to HBV-infected blood or body fluids that contain HBV. The primary risk factors associated with infection among adolescents and adults are unprotected sex with an infected partner, having multiple partners, men having sex with men, having history of other STIs, and injecting drug use (233). In addition, studies have demonstrated other modes of HBV transmission, including premastication and lapses in health care infection control procedures, as less common sources of transmission (1314–1317).
CDC’s national strategy for eliminating transmission of HBV infection includes prevention of perinatal infection through routine screening of all pregnant women for HBsAg and immunoprophylaxis of infants born to mothers with HBsAg or mothers whose HBsAg status is unknown, routine infant vaccination, vaccination of previously unvaccinated children and adolescents through age 18 years, and vaccination of previously unvaccinated adults at increased risk for infection (12). High vaccination coverage rates with subsequent decreases in acute HBV infection incidence have been achieved among infants and adolescents (1318). The vaccination of persons as children and adolescents likely has led to improved vaccination coverage among adults aged <30 years (1319) and corresponding lower rates of acute HBV infection among this group. In contrast, vaccination coverage among the majority of adult populations at high risk aged ≥30 years (e.g., persons with multiple sex partners, MSM, and injecting drug users) has remained low (1320,1321); these groups account for the highest rates of preventable acute infections (12,1319,1322). STD clinics and other health care settings providing STI services to adults at high risk for infection should administer hepatitis B vaccine to those who are unvaccinated.
Diagnosis of acute or chronic HBV infection requires serologic testing (Table 5). Because HBsAg is present in both acute and chronic infection, presence of IgM antibody to hepatitis B core antigen (IgM anti-HBc) is diagnostic of acute or recently acquired HBV infection. Antibody to HBsAg (anti-HBs) is produced after a resolved infection and is the only HBV antibody marker present after vaccination. The presence of HBsAg and anti-HBc, with a negative test for IgM anti-HBc, indicates chronic HBV infection. The presence of total anti-HBc alone might indicate acute, resolved, or chronic infection or a false-positive result.
No specific therapy is available for persons with acute HBV infection; treatment is supportive. Persons with chronic HBV infection should be referred for evaluation to a provider experienced in managing such infections. Therapeutic agents approved by FDA for treatment of chronic HBV infection can achieve sustained suppression of HBV replication and remission of liver disease (1323).
Two products have been approved for HBV prevention: hepatitis B immune globulin (HBIG) for PEP and hepatitis B vaccine (12). HBIG provides temporary (i.e., 3–6 months) protection from HBV infection and is typically used as PEP as an adjunct to hepatitis B vaccination for previously unvaccinated persons or for persons who have not responded to vaccination. HBIG is prepared from plasma known to contain high concentrations of anti-HBs. The recommended dose of HBIG is 0.06 mL/kg body weight.
Hepatitis B vaccine contains HBsAg produced in yeast by recombinant DNA technology and provides protection from HBV infection when used for both pre-exposure vaccination and PEP. The three available monovalent hepatitis B vaccines for use in the United States are Recombivax HB, Engerix-B, and Heplisav-B. A combination hepatitis A and hepatitis B vaccine for use among persons aged ≥18 years, Twinrix, also is available.
When selecting a hepatitis B vaccination schedule, health care providers should consider the need to achieve completion of the vaccine series. The recommended HBV dose and schedule varies by product and age of recipient (Table 6). Three different 3-dose schedules for adolescents and adults have been approved for both monovalent hepatitis B vaccines (i.e., Engerix-B and Recombivax HB); these vaccines can be administered at 0, 1, and 6 months; 0, 1, and 4 months; or 0, 2, and 4 months. A 4-dose schedule of Engerix-B at 0, 1, 2, and 12 months is licensed for all age groups. A 2-dose schedule of Recombivax HB adult formulation (10 µg) is licensed for adolescents aged 11–15 years, with a 4-month minimal interval between doses. When scheduled to receive the second dose, adolescents aged 16–19 years should be switched to a 3-dose series, with doses 2 and 3 consisting of the pediatric formulation (5 µg) administered on a recommended schedule. Heplisav-B is a new single-antigen recombinant hepatitis B vaccine with a novel cytosine-phosphate-guanine 1018 oligodeoxynucleotide adjuvant for prevention of HBV infection among persons aged ≥18 years, administered as a 2-dose series at 0 and 1 month (>4 weeks apart) (156). Twinrix is a 3-dose schedule administered at 0, 1, and 6 months to persons aged ≥18 years at risk for both HAV and HBV infections.
Hepatitis B vaccine should be administered IM in the deltoid muscle and can be administered simultaneously with other vaccines. If the vaccine series is interrupted after the first or second dose of vaccine, the missed dose should be administered as soon as possible. The series does not need to be restarted after a missed dose. HBV vaccination is available for eligible children and adolescents aged <19 years through the VFC program (https://www.cdc.gov/vaccines/programs/vfc/contacts-state.html). When feasible, the same manufacturer’s vaccines should be used to complete the series; however, vaccination should not be deferred when the manufacturer of the previously administered vaccine is unknown or when the vaccine from the same manufacturer is unavailable (1324).
Among adolescents and healthy adults aged <40 years, approximately 30%–55% achieve a protective antibody response (i.e., anti-HBs ≥10 mIU/mL) after the first single-antigen vaccine dose, 75% after the second, and >90% after the third. Recent clinical trials reported a protective antibody response achieved among approximately 90% of participants receiving Heplisav-B, compared with 70.5%–90.2% of participants receiving Engerix-B (12). Vaccine-induced immune memory has been demonstrated to persist for >30 years (1325–1327). Periodic testing to determine antibody levels after routine vaccination among immunocompetent persons is unnecessary, and booster doses of vaccine are not recommended.
Hepatitis B vaccination is usually well tolerated by the majority of recipients. Pain at the injection site and low-grade fever are reported by a minority of recipients. For children and adolescents, a causal association exists between receipt of hepatitis B vaccination and anaphylaxis. For each 1.1 million doses of vaccine administered, approximately one recipient will experience this type of reaction (1328); however, no deaths have been reported among these patients (1318,1328). Vaccine is contraindicated for persons with a history of anaphylaxis after a previous dose of hepatitis B vaccine and persons with a known anaphylactic reaction to any vaccine component (1329). No other adverse events after administration of hepatitis B vaccine have been demonstrated.
Hepatitis B vaccination is recommended for all unvaccinated children and adolescents; all unvaccinated adults at risk for HBV infection, especially injecting drug users; MSM; adults with multiple sex partners; sex partners, needle-sharing contacts, or household contacts of persons with chronic hepatitis B; and persons with diabetes and all adults seeking protection from HBV infection (1318). For adults, acknowledgment of a specific risk factor is not a requirement for vaccination.
Hepatitis B vaccine should be routinely offered to all unvaccinated persons attending STD clinics and to all unvaccinated persons seeking evaluation or treatment for STIs in other settings, especially correctional facilities, facilities providing substance misuse treatment and prevention services, Federally Qualified Health Centers, and settings serving MSM (e.g., HIV infection care and prevention settings). If hepatitis B vaccine is unavailable at a particular facility, persons should be linked to a setting where they can receive vaccine. Persons with a reliable vaccination history (i.e., a written, dated record of each dose of a complete series) or reliable history of hepatitis B infection (i.e., a written record of infection and serologic results providing evidence of previous infection) do not require vaccination. In all settings, vaccination should be initiated at the initial visit, even if concerns about completion of the vaccine series exist.
Prevaccination Serologic Testing
Conducting prevaccination serologic testing for susceptibility just before the initial vaccine dose is administered can be considered for identifying persons with chronic HBV infection and, potentially, reducing the cost of completing the vaccination series for adult populations that have an expected high prevalence (20%–30%) of HBV infection (e.g., injecting drug users and MSM, especially those among older age groups, or persons born where HBV endemicity is moderate to high). In addition, prevaccination testing for susceptibility is recommended for unvaccinated household, sexual, and needle-sharing contacts of HBsAg-positive persons (1318). Serologic testing should not be a barrier to vaccination. The first vaccine dose should be administered immediately after collection of the blood sample for serologic testing. Vaccination of persons who are immune to HBV infection because of current or previous infection or vaccination is not harmful and does not increase the risk for adverse events.
Prevaccination testing should be performed with HBsAg, anti-HBs, and total anti-HBc to define patients’ HBV clinical status and deliver recommended care (1330). Persons who test HBsAg positive should receive prevention counseling and evaluation for antiviral treatment (see Management of Persons Who Are HBsAg Positive). Persons who test total anti-HBc positive and anti-HBs positive should be counseled that they have had previous HBV infection and are immune. Those persons with isolated anti-HBc (i.e., negative HBsAg and anti-HBs) need further assessment to rule out occult HBV infection, and they are at higher risk for reactivation if exposed to immunosuppressants. Persons who test negative to all three HBV seromarkers should receive the complete vaccination series, with the first vaccine dose administered immediately.
Postvaccination Serologic Testing for Response
Postvaccination serologic testing for immunity is unnecessary after routine vaccination of adolescents or adults. However, such testing is recommended for persons whose subsequent clinical management depends on knowledge of their immune status. Persons recommended to receive postvaccination serologic testing include health care personnel and public safety workers, persons with HIV infection, sex and needle-sharing partners of HBsAg-positive persons, hemodialysis patients and others who might require outpatient hemodialysis (e.g., predialysis, peritoneal dialysis, or home dialysis), and other immunocompromised persons (e.g., hematopoietic stem-cell transplant recipients or persons receiving chemotherapy) (1318).
If indicated, anti-HBs testing should be performed 1–2 months after administration of the last dose of the vaccine series. Persons determined to have anti-HBs levels of <10 mIU/mL after the primary vaccine series should be revaccinated with a 3-dose series and tested again for anti-HBs 1–2 months after the third dose. Persons who do not respond to revaccination should be tested for HBsAg and HBc. If HBsAg positive, persons should receive recommended management (see Management of Persons Who Are HBsAg Positive). If HBsAg negative, persons should be considered susceptible to HBV infection and counseled about precautions for preventing HBV infection and the need for HBIG PEP for any known exposure. If isolated anti-HBc positive (i.e., negative HBsAg and anti-HBs), persons will need further assessment to rule out occult HBV infection and are at higher risk for reactivation if exposed to immunosuppressants.
Both passive and active PEP (simultaneous administration of HBIG [i.e., 0.06 mL/kg body weight] and hepatitis B vaccine at separate anatomic sites) and active PEP (administration of hepatitis B vaccination alone) have been demonstrated to be highly effective in preventing transmission after exposure to HBV (12). HBIG alone also has been demonstrated to be effective in preventing HBV transmission; however, with the availability of hepatitis B vaccine, HBIG typically is used as an adjunct to vaccination.
Exposure to a Source Who Is HBsAg Positive
Unvaccinated persons or persons known not to have responded to a complete hepatitis B vaccine series should receive both HBIG and hepatitis vaccine as soon as possible (preferably ≤24 hours) after a discrete, identifiable exposure to blood or body fluids that contain blood from a person with HBsAg (Table 7). Hepatitis B vaccine should be administered simultaneously with HBIG at a separate anatomic site, and the vaccine series should be completed by using the age-appropriate vaccine dose and schedule (Table 6). Exposed persons who are not fully vaccinated because they have not completed the vaccine series should receive HBIG (i.e., 0.06 mL/kg body weight) and complete the vaccine series. Persons who have written documentation of a complete hepatitis B vaccine series who did not receive postvaccination testing should receive a single vaccine booster dose. Exposed persons who are known to have responded to vaccination by postvaccination testing are considered protected; therefore, they need no additional doses of vaccine or HBIG. All persons with an occupational exposure to blood or body fluids that contain HBV should be managed according to guidelines (12).
Exposure to a Source with Unknown HBsAg Status
Unvaccinated persons and persons with previous nonresponse to hepatitis B vaccination who have a discrete, identifiable exposure to blood or body fluids containing blood from a person with unknown HBsAg status should receive the hepatitis B vaccine series, with the first dose initiated as soon as possible after exposure (preferably <24 hours) and the series completed according to the age-appropriate dose and schedule. Exposed persons who are not fully vaccinated but started the series should complete the vaccine series. Exposed persons with written documentation of a complete hepatitis B vaccine series who did not receive postvaccination testing require no further treatment.
Other Management Considerations
All persons with HBV infection should be tested for HIV, syphilis, gonorrhea, and chlamydia.
Management of Persons Who Are HBsAg Positive
Recommendations for management of all persons with HBsAg include the following:
- All persons with HBsAg documented on laboratory results should be reported to the state or local health department.
- To verify the presence of chronic HBV infection, persons with HBsAg should be retested. The absence of IgM anti-HBc or the persistence of HBsAg for ≥6 months indicates chronic HBV infection.
- Persons with chronic HBV infection should be referred for evaluation to a specialist experienced in managing chronic hepatitis B infection.
- Household, sexual, and needle-sharing contacts of persons with chronic infection should be evaluated. Unvaccinated sex partners and household and needle-sharing contacts should be tested for susceptibility to HBV infection and receive the first dose of hepatitis B vaccine immediately after collection of the blood sample for serologic testing (see Prevaccination Serologic Testing). Susceptible persons should complete the vaccine series by using an age-appropriate vaccine dose and schedule.
- Sex partners of persons with HBsAg should be counseled to use latex condoms (1331) to protect themselves from sexual exposure to infectious body fluids (e.g., semen and vaginal secretions), unless they have been demonstrated to be immune after vaccination (anti-HBs ≥10 mIU/mL) or previously infected (anti-HBc positive).
- To prevent or reduce the risk for transmission to others in addition to vaccination, persons with HBsAg also should be advised to
- use methods (e.g., condoms) to protect nonimmune sex partners from acquiring HBV infection from sexual activity until the partner can be vaccinated and immunity documented;
- cover cuts and skin lesions to prevent spread by infectious secretions or blood;
- refrain from donating blood, plasma, body organs, other tissue, or semen; and
- refrain from sharing household articles (e.g., toothbrushes, razors, or personal injecting equipment) that could become contaminated with blood, and refrain from premastication of food.
- To protect the liver from further harm, persons with HBsAg should be advised to
- avoid or limit alcohol consumption because of the effects of alcohol on the liver;
- refrain from starting any new medicines, including over-the-counter and herbal medicines, without checking with their health care provider; and
- obtain vaccination against hepatitis A.
When seeking medical or dental care, persons who are HBsAg positive should be advised to inform their health care providers of their HBsAg status so that they can be evaluated and managed. The following are key counseling messages for persons with HBsAg:
- HBV is not usually spread by hugging, coughing, food or water, sharing eating utensils or drinking glasses, or casual contact.
- Persons should not be excluded from work, school, play, childcare, or other settings because they are infected with HBV.
- Involvement with a support group might help patients cope with chronic HBV infection.
- HBV infection is a chronic condition that can be treated, and patients should receive prevention counseling and be evaluated for antiviral treatment.
Regardless of whether they have been previously tested or vaccinated, all pregnant women should be tested for HBsAg at the first prenatal visit and again at delivery if at high risk for HBV infection (see STI Detection Among Special Populations). Pregnant women at risk for HBV infection and without documentation of a complete hepatitis B vaccine series should receive hepatitis B vaccination. All pregnant women with HBsAg should be reported to state and local perinatal hepatitis B prevention programs and referred to a specialist. Information about management of pregnant women with HBsAg and their infants is available at https://www.cdc.gov/hepatitis/hbv/perinatalxmtn.htm.
HIV infection can impair the response to hepatitis B vaccination. Persons with HIV should be tested for anti-HBs 1–2 months after the third vaccine dose (see Postvaccination Serologic Testing). Modified dosing regimens, including a doubling of the standard antigen dose and administration of additional doses, might increase the response rate and should be managed in consultation with an infectious disease specialist. Additional recommendations for management of persons with HBsAg and HIV infection are available (98).