Table 1.

HBsAg	Total anti-HBc	IgM anti-HBc	Anti-HBs	HBV DNA	Interpretation
–	–	–	–	–	Never infected
+	–	–	–	+ or –	Early acute infection; transient (up to 18 days) after vaccination
+	+	+	–	+	Acute infection
–	+	+	+ or –	+ or –	Acute resolving infection
–	+	–	+	–	Recovered from past infection and immune
+	+	–	–	+	Chronic infection
–	+	–	–	+ or –	False-positive (i.e., susceptible); past infection; “low-level” chronic infection; or passive transfer of anti-HBc to infant born to HBsAg-positive mother
–	–	–	+	–	Immune if anti-HBs concentration is ≥10 mIU/mL after vaccine series completion; passive transfer after hepatitis B immune globulin administration

Table 1. Typical interpretation of test results for hepatitis B virus infection

Abbreviations: – = negative; + = positive; anti-HBc = antibody to hepatitis B core antigen; anti-HBs = antibody to hepatitis B surface antigen; HBsAg = hepatitis B surface antigen; HBV DNA = hepatitis B virus deoxyribonucleic acid; IgM = immunoglobulin class M.

Table 2.

Age group (yrs)	Single-antigen vaccine					Combination vaccine
	Recombivax		Engerix			Pediarix*		Twinrix^†
	Dose (µg)	Vol (mL)		Dose (µg)	Vol (mL)	Dose (µg)	Vol (mL)	Dose (µg)	Vol (mL)
Birth–10	5	0.5		10	0.5	10*	0.5	N/A	N/A
11–15	10^§	1		N/A	N/A	N/A	N/A	N/A	N/A
11–19	5	0.5		10	0.5	N/A	N/A	N/A	N/A
≥20	10	1		20	1	N/A	N/A	20^†	1
Hemodialysis patients and other immune-compromised persons
<20	5	0.5		10	0.5	N/A	N/A	N/A	N/A
≥20	40	1		40	2	N/A	N/A	N/A	N/A

Table 2. Recommended doses of hepatitis B vaccine, by group and vaccine type

Abbreviation: N/A = not applicable.
* Pediarix is approved for use in persons aged 6 weeks through 6 years (prior to the 7th birthday).
^† Twinrix is approved for use in persons aged ≥18 years.
^§ Adult formulation administered on a 2-dose schedule.

Table 3.

Birthweight	Maternal HBsAg status	Single-antigen vaccine		Single-antigen + combination vaccine
Birthweight	Maternal HBsAg status	Dose	Age	Dose	Age
≥2,000 g	Positive	1	Birth (≤12 hrs)	1	Birth (≤12 hrs)
		HBIG^§	Birth (≤12 hrs)	HBIG	Birth (≤12 hrs)
		2	1–2 mos	2	2 mos
		3	6 mos^¶	3	4 mos
		3	6 mos^¶	4	6 mos^¶
	Unknown*	1	Birth (≤12 hrs)	1	Birth (≤12 hrs)
		2	1–2 mos	2	2 mos
		3	6 mos^¶	3	4 mos
		3	6 mos^¶	4	6 mos^¶
	Negative	1	Birth (≤24 hrs)	1	Birth (≤24 hrs)
		2	1–2 mos	2	2 mos
		3	6–18 mos^¶	3	4 mos
		3	6–18 mos^¶	4	6 mos^¶
<2,000 g	Positive	1	Birth (≤12 hrs)	1	Birth (≤12 hrs)
		HBIG	Birth (≤12 hrs)	HBIG	Birth (≤12 hrs)
		2	1 mos	2	2 mos
		3	2–3 mos	3	4 mos
		4	6 mos^¶	4	6 mos^¶
	Unknown	1	Birth (≤12 hrs)	1	Birth (≤12 hrs)
		HBIG	Birth (≤12 hrs)	HBIG	Birth (≤12 hrs)
		2	1 mos	2	2 mos
		3	2–3 mos	3	4 mos
		4	6 mos^¶	4	6 mos^¶
	Negative	1	Hospital discharge or age 1 mo	1	Hospital discharge or age 1 mo
		2	2 mos	2	2 mos
		3	6–18 mos^¶	3	4 mos
		3	6–18 mos^¶	4	6 mos^¶

Table 3. Hepatitis B vaccine schedules for infants, by infant birthweight and maternal HBsAg status

Abbreviations: HBIG = hepatitis B immune globulin; HBsAg = hepatitis B surface antigen.
* Mothers should have blood drawn and tested for HBsAg as soon as possible after admission for delivery; if the mother is found to be HBsAg positive, the infant should receive HBIG as soon as possible but no later than age 7 days.
^† Pediarix should not be administered before age 6 weeks.
^§ HBIG should be administered at a separate anatomical site from vaccine.
^¶ The final dose in the vaccine series should not be administered before age 24 weeks (164 days).

Table 4.

Age group	Schedule* (interval represents time in months from first dose)
Children (1–10 yrs)	0, 1, and 6 mos
Children (1–10 yrs)	0, 1, 2, and 12 mos
Adolescents (11–19 yrs)	0, 1, and 6 mos
	0, 12, and 24 mos
	0 and 4–6 mos^†
	0, 1, 2, and 12 mos 0, 7 days, 21–30 days, 12 mos^§
Adults (≥20 yrs)	0, 1, and 6 mos
Adults (≥20 yrs)	0, 1, 2, and 12 mos 0, 1, 2, and 6 mos^¶ 0, 7 days, 21–30 days, 12 mos^§

Table 4. Hepatitis B vaccine schedules for children, adolescents, and adults

* Refer to package inserts for further information. For all ages, when the HepB vaccine schedule is interrupted, the vaccine series does not need to be restarted. If the series is interrupted after the first dose, the second dose should be administered as soon as possible, and the second and third doses should be separated by an interval of at least 8 weeks. If only the third dose has been delayed, it should be administered as soon as possible. The final dose of vaccine must be administered at least 8 weeks after the second dose and should follow the first dose by at least 16 weeks; the minimum interval between the first and second doses is 4 weeks. Inadequate doses of hepatitis B vaccine or doses received after a shorter-than-recommended dosing interval should be readministered, using the correct dosage or schedule. Vaccine doses administered ≤4 days before the minimum interval or age are considered valid. Because of the unique accelerated schedule for Twinrix, the 4-day guideline does not apply to the first three doses of this vaccine when administered on a 0-day, 7-day, 21–30-day, and 12-month schedule (new recommendation).
^†A 2-dose schedule of Recombivax adult formulation (10 µg) is licensed for adolescents aged 11–15 years. When scheduled to receive the second dose, adolescents aged >15 years should be switched to a 3-dose series, with doses 2 and 3 consisting of the pediatric formulation administered on an appropriate schedule.
^§ Twinrix is approved for use in persons aged ≥18 years and is available on an accelerated schedule with doses administered at 0, 7, 21–30 days, and 12 months.
^¶ A 4-dose schedule of Engerix administered in two 1 mL doses (40 µg) on a 0-, 1-, 2-, and 6-month schedule is recommended for adult hemodialysis patients.

Table 5.

HCP status	Postexposure testing		Postexposure prophylaxis		Postvaccination serologic testing
HCP status	Source patient (HBsAg)	HCP testing (anti-HBs)	HBIG	Vaccination	Postvaccination serologic testing
Documented responder after complete series			No action needed
Documented nonresponder after two complete series	Positive/unknown	–*	HBIG x2 separated by 1 month	–	N/A
Documented nonresponder after two complete series	Negative			No action needed
Response unknown after complete series	Positive/unknown	<10 mIU/mL	HBIG x1	Initiate revaccination	Yes
	Negative	<10 mIU/mL	None
	Any result	<10 mIU/mL		No action needed
Unvaccinated/incompletely vaccinated or vaccine refusers	Positive/unknown	–	HBIG x1	Complete vaccination	Yes
Unvaccinated/incompletely vaccinated or vaccine refusers	Negative	–	None	Complete vaccination	Yes

Table 5. Postexposure management of health care personnel after occupational percutaneous or mucosal exposure to blood or body fluids, by health care personnel HepB vaccination and response status

Abbreviations: anti HBs = antibody to hepatitis B surface antigen; HBIG = hepatitis B immune globulin; HBsAg = hepatitis B surface antigen; HCP = health care personnel; N/A = not applicable.
* Not indicated.

Table 6.

Exposure*	Management
Exposure*	Unvaccinated person	Previously vaccinated person
HBsAg-positive source	HepB vaccine series and HBIG	HepB vaccine dose
HBsAg status unknown for source	Hep B vaccine series	No management

Table 6. Postexposure management after distinct nonoccupational percutaneous or mucosal exposure to blood or body fluids

Abbreviations: HepB = hepatitis B; HBsAg = hepatitis B surface antigen; HBIG = hepatitis B immune globulin.
* Exposures include percutaneous (e.g., bite or needlestick) or mucosal exposure to blood or body fluids, sex or needle-sharing contact, or victim of sexual assault/abuse.

Box 1.

AASLD	American Association for the Study of Liver Diseases
ACIP	Advisory Committee on Immunization Practices
anti-HBc	antibody to hepatitis B core antigen
anti-HBe	antibody to hepatitis B e antigen
anti-HBs	antibody to hepatitis B surface antigen
HBeAg	hepatitis B e antigen
HBIG	hepatitis B immune globulin
HBsAg	hepatitis B surface antigen
HBV	hepatitis B virus
HBV	DNA hepatitis B virus deoxyribonucleic acid
HCP	health care personnel
HCV	hepatitis C virus
HepB	hepatitis B
HIV	human immunodeficiency virus
IDSA	Infectious Diseases Society of America
IDU	Injection-drug use
IgM	Immunoglobulin class M
IgG	Immunoglobulin class G
MSM	men who have sex with men
NNDSS	National Notifiable Diseases Surveillance System
PHBPP	Perinatal Hepatitis B Prevention Program
PWID	persons who inject drugs
QALY	quality-adjusted life-year
STI	sexually transmitted infection
VAERS	Vaccine Adverse Events Reporting System
VSD	Vaccine Safety Datalink

Box 1. Abbreviations used in this report

Box 2.

Screening of all pregnant women for HBsAg --HBV DNA testing for HBsAg-positive pregnant women, with suggestion of maternal antiviral therapy to reduce perinatal transmission when HBV DNA is >200,000 IU/mL --Prophylaxis (HepB vaccine and HBIG) for infants born to HBsAg-positive^† women Universal vaccination of all infants beginning at birth^§,¶ as a safeguard for infants born to HBV-infected mothers not identified prenatally Routine vaccination of previously unvaccinated children aged <19 years Vaccination of adults at risk for HBV infection, including those requesting protection from HBV without acknowledgment of a specific risk factor

Screening of all pregnant women for HBsAg
- --HBV DNA testing for HBsAg-positive pregnant women, with suggestion of maternal antiviral therapy to reduce perinatal transmission when HBV DNA is >200,000 IU/mL
- --Prophylaxis (HepB vaccine and HBIG) for infants born to HBsAg-positive^† women
Universal vaccination of all infants beginning at birth^§,¶ as a safeguard for infants born to HBV-infected mothers not identified prenatally
Routine vaccination of previously unvaccinated children aged <19 years
Vaccination of adults at risk for HBV infection, including those requesting protection from HBV without acknowledgment of a specific risk factor

Box 2. Strategy to eliminate HBV transmission in the United States*

*Sources: Mast EE, Margolis HS, 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 1: immunization of infants, children, and adolescents. MMWR Recomm Rep 2005;54(No. RR-16):1–31; 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(No. RR-16):1–33.
^†Refer to Table 3 for prophylaxis recommendations for infants born to women with unknown HBsAg status.
^§Within 24 hours of birth for medically stable infants weighing ≥2,000 grams.
^¶Refer to Table 3 for birth dose recommendations for infants weighing <2,000 grams.

Box 3.

High (≥8% prevalence): Angola, Benin, Burkina Faso, Burundi, Cameroon, Central African Republic, Congo, Côte d’Ivoire, Djibouti, Equatorial Guinea, Gabon, Gambia, Ghana, Guinea, Haiti, Kiribati, Kyrgyzstan, Laos, Liberia, Malawi, Mali, Mauritania, Mongolia, Mozambique, Namibia, Nauru, Niger, Nigeria, Niue, Papua New Guinea, Senegal, Sierra Leone, Solomon Islands, Somalia, South Sudan, Sudan, Swaziland, Togo, Tonga, Uganda, Vanuatu, Vietnam, Yemen, and Zimbabwe. Intermediate (5%–7.9% prevalence): Albania, Bhutan, Cape Verde, China, Democratic Republic of the Congo, Ethiopia, Kazakhstan, Kenya, Marshall Islands, Moldova, Oman, Romania, Rwanda, Samoa, South Africa, Tajikistan, Tanzania, Thailand, Tunisia, Tuvalu, Uzbekistan, and Zambia Low Intermediate (2%–4.9% prevalence): Algeria, Azerbaijan, Bangladesh, Belarus, Belize, Brunei Darussalam, Bulgaria, Cambodia, Colombia, Cyprus, Dominican Republic, Ecuador, Eritrea, Federated States of Micronesia, Fiji, Georgia, Italy, Jamaica, Kosovo, Libya, Madagascar, Myanmar, New Zealand, Pakistan, Palau, Philippines, Peru, Russia, Saudi Arabia, Singapore, South Korea, Sri Lanka, Suriname, Syria, Tahiti, and Turkey. Low (≤1.9% prevalence): Afghanistan, Argentina, Australia, Austria, Bahrain, Barbados, Belgium, Bolivia, Bosnia and Herzegovina, Brazil, Canada, Chile, Costa Rica, Croatia, Cuba, Czech Republic, Denmark, Egypt, France, Germany, Greece, Guatemala, Hungary, Iceland, India, Indonesia, Iran, Iraq, Ireland, Israel, Japan, Jordan, Kuwait, Lebanon, Lithuania, Malaysia, Mexico, Morocco, Nepal, Netherlands, Nicaragua, Norway, Palestine, Panama, Poland, Portugal, Qatar, Serbia, Seychelles, Slovakia, Slovenia, Spain, Sweden, Switzerland, Ukraine, UK, United Arab Emirates, United States of America, and Venezuela. No data: Andorra, Antigua and Barbuda, Armenia, The Bahamas, Botswana, Chad, Comoros, Cook Islands, Dominica, El Salvador, Finland, Grenada, Guinea- Bissau, Guyana, Honduras, Latvia, Lesotho, Lithuania, Luxembourg, Macedonia, Maldives, Malta, Mauritius, Monaco, Montenegro, North Korea, Paraguay, Saint Kitts and Nevis, Saint Lucia, Saint Vincent and the Grenadines, San Marino, Sao Tome and Principe, Timor-Leste, Trinidad and Tobago, Turkmenistan, and Uruguay.

High (≥8% prevalence): Angola, Benin, Burkina Faso, Burundi, Cameroon, Central African Republic, Congo, Côte d’Ivoire, Djibouti, Equatorial Guinea, Gabon, Gambia, Ghana, Guinea, Haiti, Kiribati, Kyrgyzstan, Laos, Liberia, Malawi, Mali, Mauritania, Mongolia, Mozambique, Namibia, Nauru, Niger, Nigeria, Niue, Papua New Guinea, Senegal, Sierra Leone, Solomon Islands, Somalia, South Sudan, Sudan, Swaziland, Togo, Tonga, Uganda, Vanuatu, Vietnam, Yemen, and Zimbabwe.

Intermediate (5%–7.9% prevalence): Albania, Bhutan, Cape Verde, China, Democratic Republic of the Congo, Ethiopia, Kazakhstan, Kenya, Marshall Islands, Moldova, Oman, Romania, Rwanda, Samoa, South Africa, Tajikistan, Tanzania, Thailand, Tunisia, Tuvalu, Uzbekistan, and Zambia

Low Intermediate (2%–4.9% prevalence): Algeria, Azerbaijan, Bangladesh, Belarus, Belize, Brunei Darussalam, Bulgaria, Cambodia, Colombia, Cyprus, Dominican Republic, Ecuador, Eritrea, Federated States of Micronesia, Fiji, Georgia, Italy, Jamaica, Kosovo, Libya, Madagascar, Myanmar, New Zealand, Pakistan, Palau, Philippines, Peru, Russia, Saudi Arabia, Singapore, South Korea, Sri Lanka, Suriname, Syria, Tahiti, and Turkey.

Low (≤1.9% prevalence): Afghanistan, Argentina, Australia, Austria, Bahrain, Barbados, Belgium, Bolivia, Bosnia and Herzegovina, Brazil, Canada, Chile, Costa Rica, Croatia, Cuba, Czech Republic, Denmark, Egypt, France, Germany, Greece, Guatemala, Hungary, Iceland, India, Indonesia, Iran, Iraq, Ireland, Israel, Japan, Jordan, Kuwait, Lebanon, Lithuania, Malaysia, Mexico, Morocco, Nepal, Netherlands, Nicaragua, Norway, Palestine, Panama, Poland, Portugal, Qatar, Serbia, Seychelles, Slovakia, Slovenia, Spain, Sweden, Switzerland, Ukraine, UK, United Arab Emirates, United States of America, and Venezuela.

No data: Andorra, Antigua and Barbuda, Armenia, The Bahamas, Botswana, Chad, Comoros, Cook Islands, Dominica, El Salvador, Finland, Grenada, Guinea- Bissau, Guyana, Honduras, Latvia, Lesotho, Lithuania, Luxembourg, Macedonia, Maldives, Malta, Mauritius, Monaco, Montenegro, North Korea, Paraguay, Saint Kitts and Nevis, Saint Lucia, Saint Vincent and the Grenadines, San Marino, Sao Tome and Principe, Timor-Leste, Trinidad and Tobago, Turkmenistan, and Uruguay.

Box 3. Prevalence of chronic hepatitis B virus infection, by country*

* Source: CDC. Travelers health: infectious diseases related to travel. Atlanta, GA: US Department of Health and Human Services, CDC; 2017.

Box 4.

All infants Unvaccinated children aged <19 years Persons at risk for infection by sexual exposure --Sex partners of hepatitis B surface antigen (HBsAg)–positive persons --Sexually active persons who are not in a long-term, mutually monogamous relationship (e.g., persons with more than one sex partner during the previous 6 months) --Persons seeking evaluation or treatment for a sexually transmitted infection --Men who have sex with men Persons at risk for infection by percutaneous or mucosal exposure to blood --Current or recent injection-drug users --Household contacts of HBsAg-positive persons --Residents and staff of facilities for developmentally disabled persons --Health care and public safety personnel with reasonably anticipated risk for exposure to blood or blood-contaminated body fluids --Hemodialysis patients and predialysis, peritoneal dialysis, and home dialysis patients --Persons with diabetes aged 19–59 years; persons with diabetes aged ≥60 years at the discretion of the treating clinician Others --International travelers to countries with high or intermediate levels of endemic hepatitis B virus (HBV) infection (HBsAg prevalence of ≥2%) --Persons with hepatitis C virus infection --Persons with chronic liver disease (including, but not limited to, persons with cirrhosis, fatty liver disease, alcoholic liver disease, autoimmune hepatitis, and an alanine aminotransferase [ALT] or aspartate aminotransferase [AST] level greater than twice the upper limit of normal) --Persons with HIV infection --Incarcerated persons --All other persons seeking protection from HBV infection

All infants
Unvaccinated children aged <19 years
Persons at risk for infection by sexual exposure
- --Sex partners of hepatitis B surface antigen (HBsAg)–positive persons
- --Sexually active persons who are not in a long-term, mutually monogamous relationship (e.g., persons with more than one sex partner during the previous 6 months)
- --Persons seeking evaluation or treatment for a sexually transmitted infection
- --Men who have sex with men
Persons at risk for infection by percutaneous or mucosal exposure to blood
- --Current or recent injection-drug users
- --Household contacts of HBsAg-positive persons
- --Residents and staff of facilities for developmentally disabled persons
- --Health care and public safety personnel with reasonably anticipated risk for exposure to blood or blood-contaminated body fluids
- --Hemodialysis patients and predialysis, peritoneal dialysis, and home dialysis patients
- --Persons with diabetes aged 19–59 years; persons with diabetes aged ≥60 years at the discretion of the treating clinician
Others
- --International travelers to countries with high or intermediate levels of endemic hepatitis B virus (HBV) infection (HBsAg prevalence of ≥2%)
- --Persons with hepatitis C virus infection
- --Persons with chronic liver disease (including, but not limited to, persons with cirrhosis, fatty liver disease, alcoholic liver disease, autoimmune hepatitis, and an alanine aminotransferase [ALT] or aspartate aminotransferase [AST] level greater than twice the upper limit of normal)
- --Persons with HIV infection
- --Incarcerated persons
- --All other persons seeking protection from HBV infection

Box 4. Persons recommended to receive hepatitis B vaccination

Box 5.

The issue: An increasing number of HCP have received routine hepatitis B (HepB) vaccination during childhood. No postvaccination serologic testing is recommended after routine infant or adolescent HepB vaccination. Because vaccine-induced antibody to hepatitis B surface antigen (anti-HBs) wanes over time, testing HCP for anti-HBs years after vaccination might not distinguish vaccine nonresponders from responders. Guidance for health care institutions: Health care institutions may measure anti-HBs upon hire or matriculation for HCP who have documentation of a complete HepB vaccine series in the past (e.g., as part of routine infant or adolescent vaccination). HCP with anti-HBs <10 mIU/mL should receive one or more additional doses of HepB vaccine and retesting (Figure 3). Institutions that decide to not measure anti-HBs upon hire or matriculation for HCP who have documentation of a complete HepB vaccine series in the past should ensure timely assessment and postexposure prophylaxis following an exposure (Table 5). Considerations: The risk for occupational HBV infection for vaccinated HCP might be low enough in certain settings so that assessment of anti-HBs status and appropriate follow-up should be done at the time of exposure to potentially infectious blood or body fluids. This approach relies on HCP recognizing and reporting blood and body fluid exposures and therefore may be applied on the basis of documented low risk, implementation, and cost considerations. Certain HCP occupations have lower risk for occupational blood and body fluid exposures (e.g., occupations involving counseling versus performing procedures), and nontrainees have lower risks for blood and body fluid exposures than trainees. Some settings also will have a lower prevalence of HBV infection in the patient population served than in other settings, which will influence the risk for HCP exposure to HBsAg-positive blood and body fluids.

The issue: An increasing number of HCP have received routine hepatitis B (HepB) vaccination during childhood. No postvaccination serologic testing is recommended after routine infant or adolescent HepB vaccination. Because vaccine-induced antibody to hepatitis B surface antigen (anti-HBs) wanes over time, testing HCP for anti-HBs years after vaccination might not distinguish vaccine nonresponders from responders.

Guidance for health care institutions: Health care institutions may measure anti-HBs upon hire or matriculation for HCP who have documentation of a complete HepB vaccine series in the past (e.g., as part of routine infant or adolescent vaccination). HCP with anti-HBs <10 mIU/mL should receive one or more additional doses of HepB vaccine and retesting (Figure 3). Institutions that decide to not measure anti-HBs upon hire or matriculation for HCP who have documentation of a complete HepB vaccine series in the past should ensure timely assessment and postexposure prophylaxis following an exposure (Table 5).

Considerations: The risk for occupational HBV infection for vaccinated HCP might be low enough in certain settings so that assessment of anti-HBs status and appropriate follow-up should be done at the time of exposure to potentially infectious blood or body fluids. This approach relies on HCP recognizing and reporting blood and body fluid exposures and therefore may be applied on the basis of documented low risk, implementation, and cost considerations. Certain HCP occupations have lower risk for occupational blood and body fluid exposures (e.g., occupations involving counseling versus performing procedures), and nontrainees have lower risks for blood and body fluid exposures than trainees. Some settings also will have a lower prevalence of HBV infection in the patient population served than in other settings, which will influence the risk for HCP exposure to HBsAg-positive blood and body fluids.

Box 5. Testing anti-HBs for health care personnel (HCP) vaccinated in the past

Box 6.

Household, sexual, or needle contacts of hepatitis B surface antigen (HBsAg)–positive persons^† HIV-positive persons^† Persons with elevated alanine aminotransferase/aspartate aminotransferase of unknown etiology^† Hemodialysis patients^† Men who have sex with men^† Past or current persons who inject drugs^† Persons born in countries of high and intermediate hepatitis B virus (HBV) endemicity (HBsAg prevalence ≥2%) U.S.-born persons not vaccinated as infants whose parents were born in countries with high HBV endemicity (≥8%) Persons needing immunosuppressive therapy, including chemotherapy, immunosuppression related to organ transplantation, and immunosuppression for rheumatologic or gastroenterologic disorders Donors of blood, plasma, organs, tissues, or semen

Household, sexual, or needle contacts of hepatitis B surface antigen (HBsAg)–positive persons^†
HIV-positive persons^†
Persons with elevated alanine aminotransferase/aspartate aminotransferase of unknown etiology^†
Hemodialysis patients^†
Men who have sex with men^†
Past or current persons who inject drugs^†
Persons born in countries of high and intermediate hepatitis B virus (HBV) endemicity (HBsAg prevalence ≥2%)
U.S.-born persons not vaccinated as infants whose parents were born in countries with high HBV endemicity (≥8%)
Persons needing immunosuppressive therapy, including chemotherapy, immunosuppression related to organ transplantation, and immunosuppression for rheumatologic or gastroenterologic disorders
Donors of blood, plasma, organs, tissues, or semen

Box 6. Persons recommended to receive serologic testing prior to vaccination*

* Serologic testing comprises testing for hepatitis B surface antigen (HBsAg), antibody to HBsAg, and antibody to hepatitis B core antigen.
^† Denotes persons also recommended for hepatitis B vaccination. Serologic testing should occur prior to vaccination. Serologic testing should not be a barrier to vaccination of susceptible persons. The first dose of vaccine should typically be administered immediately after collection of the blood for serologic testing.

Box 7.

Infants born to hepatitis B surface antigen (HBsAg)–positive mothers or mothers whose HBsAg status remains unknown (e.g., when a parent or person with lawful custody safely surrenders an infant confidentially shortly after birth infants safely surrendered at or shortly after birth)^† Health care personnel and public safety workers Hemodialysis patients and others who might require outpatient hemodialysis (e.g., predialysis, peritoneal dialysis, and home dialysis) HIV-infected persons Other immunocompromised persons (e.g., hematopoietic stem-cell transplant recipients or persons receiving chemotherapy) Sex partners of HBsAg-positive persons

Infants born to hepatitis B surface antigen (HBsAg)–positive mothers or mothers whose HBsAg status remains unknown (e.g., when a parent or person with lawful custody safely surrenders an infant confidentially shortly after birth infants safely surrendered at or shortly after birth)^†
Health care personnel and public safety workers
Hemodialysis patients and others who might require outpatient hemodialysis (e.g., predialysis, peritoneal dialysis, and home dialysis)
HIV-infected persons
Other immunocompromised persons (e.g., hematopoietic stem-cell transplant recipients or persons receiving chemotherapy)
Sex partners of HBsAg-positive persons

Box 7. Persons recommended to receive postvaccination serologic testing* following a complete series of HepB vaccination

* Postvaccination serologic testing for persons other than infants born to HBsAg-positive (or HBsAg-unknown) mothers consists of anti-HBs.
^† Postvaccination serologic testing for infants born to HBsAg-positive (or HBsAg-unknown) mothers consists of anti-HBs and HBsAg. Persons with anti-HBs <10 mIU/mL after the primary vaccine series should be revaccinated. Infants born to HBsAg-positive mothers or mothers with an unknown HBsAg status should be revaccinated with a single dose of HepB vaccine and receive postvaccination serologic testing 1–2 months later. Infants whose anti-HBs remains <10 mIU/mL following single dose revaccination should receive two additional doses of HepB vaccine, followed by postvaccination serologic testing 1–2 months after the final dose. Based on clinical circumstances or family preference, HBsAg-negative infants with anti-HBs <10 mIU/mL may instead be revaccinated with a second, complete 3-dose series, followed by postvaccination serologic testing performed 1–2 months after the final dose of vaccine. For others with anti-HBs <10 mIU/mL after the primary series, administration of 3 additional HepB vaccine doses on an appropriate schedule, followed by anti-HBs testing 1–2 months after the final dose, is usually more practical than serologic testing after ≥1 dose of vaccine.

CDC. Updated U.S. Public Health Service guidelines for the management of occupational exposures to HBV, HCV, and HIV and recommendations for postexposure prophylaxis. MMWR Recomm Rep 2001;50(No. RR-11):1–52. PubMed
Preboth M. PHS guidelines for management of occupational exposure to HBV, HCV and HIV: management of occupational blood exposures. Am Fam Physician 2001;64:2012–4. PubMed
Bond WW, Favero MS, Petersen NJ, Gravelle CR, Ebert JW, Maynard JE. Survival of hepatitis B virus after drying and storage for one week. Lancet 1981;317:550–1. CrossRef PubMed
CDC. Viral hepatitis—statistics and surveillance. Atlanta, GA: US Department of Health and Human Services, CDC; 2017. https://www.cdc.gov/hepatitis/statistics/
Terrault NA, Bzowej NH, Chang KM, Hwang JP, Jonas MM, Murad MH; American Association for the Study of Liver Diseases. AASLD guidelines for treatment of chronic hepatitis B. Hepatology 2016;63:261–83. CrossRef PubMed
Rubin LG, Levin MJ, Ljungman P, et al. ; Infectious Diseases Society of America. 2013 IDSA clinical practice guideline for vaccination of the immunocompromised host. Clin Infect Dis 2014;58:e44–100. CrossRef PubMed
Mast EE, Margolis HS, Fiore AE, et al. ; Advisory Committee on Immunization Practices (ACIP). 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 1: immunization of infants, children, and adolescents. MMWR Recomm Rep 2005;54(No. RR-16):1–31. PubMed
Mast EE, Weinbaum CM, Fiore AE, et al. ; Advisory Committee on Immunization Practices (ACIP) Centers for Disease Control and Prevention (CDC). 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(No. RR-16):1–33, quiz CE1–4. PubMed
CDC. Use of hepatitis B vaccination for adults with diabetes mellitus: recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Morb Mortal Wkly Rep 2011;60:1709–11. PubMed
Schillie S, Murphy TV, Sawyer M, et al. CDC guidance for evaluating health-care personnel for hepatitis B virus protection and for administering postexposure management. MMWR Recomm Rep 2013;62(No. RR-10):1–19. PubMed
Schillie S, Murphy TV, Fenlon N, Ko S, Ward JW. Update: shortened interval for postvaccination serologic testing of infants born to hepatitis b-infected mothers. MMWR Morb Mortal Wkly Rep 2015;64:1118–20. CrossRef PubMed
Shimabukuro TT, Nguyen M, Martin D, DeStefano F. Safety monitoring in the Vaccine Adverse Event Reporting System (VAERS). Vaccine 2015;33:4398–405. CrossRef PubMed
Zhou W, Pool V, Iskander JK, et al. Surveillance for safety after immunization: Vaccine Adverse Event Reporting System (VAERS)—United States, 1991–2001. MMWR Surveill Summ 2003;52(No. SS-1):1–24. PubMed
McNeil MM, Gee J, Weintraub ES, et al. The Vaccine Safety Datalink: successes and challenges monitoring vaccine safety. Vaccine 2014;32:5390–8. CrossRef PubMed
CDC. Surveillance data for acute viral hepatitis—United States, 2008. Atlanta, GA: US Department of Health and Human Services, CDC; 2010. https://www.cdc.gov/hepatitis/statistics/2008surveillance/index.htm
Harris AM, Iqbal K, Schillie S, et al. Increases in acute hepatitis B virus infections—Kentucky, Tennessee, and West Virginia, 2006–2013. MMWR Morb Mortal Wkly Rep 2016;65:47–50. CrossRef PubMed
Roberts H, Kruszon-Moran D, Ly KN, et al. Prevalence of chronic hepatitis B virus (HBV) infection in U.S. households: National Health and Nutrition Examination Survey (NHANES), 1988-2012. Hepatology 2016;63:388–97. CrossRef PubMed
Wasley A, Kruszon-Moran D, Kuhnert W, et al. The prevalence of hepatitis B virus infection in the United States in the era of vaccination. J Infect Dis 2010;202:192–201. CrossRef PubMed
Kowdley KV, Wang CC, Welch S, Roberts H, Brosgart CL. Prevalence of chronic hepatitis B among foreign-born persons living in the United States by country of origin. Hepatology 2012;56:422–33. CrossRef PubMed
Mitchell T, Armstrong GL, Hu DJ, Wasley A, Painter JA. The increasing burden of imported chronic hepatitis B—United States, 1974–2008. PLoS One 2011;6:e27717. CrossRef PubMed
CDC. Hepatitis B virus: a comprehensive strategy for eliminating transmission in the United States through universal childhood vaccination. Recommendations of the Immunization Practices Advisory Committee (ACIP). MMWR Recomm Rep 1991;40(No. RR-13):1–25. PubMed
CDC. Recommendation of the Immunization Practices Advisory Committee (ACIP). Inactivated hepatitis B virus vaccine. MMWR Morb Mortal Wkly Rep 1982;31:317–22, 327–8. PubMed
CDC. Changing patterns of groups at high risk for hepatitis B in the United States. MMWR Morb Mortal Wkly Rep 1988;37:429–32, 437. PubMed
CDC. Update: universal precautions for prevention of transmission of human immunodeficiency virus, hepatitis B virus, and other bloodborne pathogens in health-care settings. MMWR Morb Mortal Wkly Rep 1988;37:377–82, 387–8. PubMed
CDC. Prevention of perinatal transmission of hepatitis B virus: prenatal screening of all pregnant women for hepatitis B surface antigen. MMWR Morb Mortal Wkly Rep 1988;37:341–6, 351. PubMed
CDC. Update: recommendations to prevent hepatitis B virus transmission—United States. MMWR Morb Mortal Wkly Rep 1999;48:33–4. PubMed
Kolasa MS, Tsai Y, Xu J, Fenlon N, Schillie S. Hepatitis B surface antigen testing among pregnant women, United States 2014. Pediatr Infect Dis J 2017;36:e175–80. CrossRef PubMed
Kubo A, Shlager L, Marks AR, et al. Prevention of vertical transmission of hepatitis B: an observational study. Ann Intern Med 2014;160:828–35. CrossRef PubMed
Schillie S, Walker T, Veselsky S, et al. Outcomes of infants born to women infected with hepatitis B. Pediatrics 2015;135:e1141–7. CrossRef PubMed
Hill HA, Elam-Evans LD, Yankey D, Singleton JA, Kang Y. Vaccination coverage among children aged 19–35 months—United States, 2016. MMWR Morb Mortal Wkly Rep 2017;66:1171–7. CrossRef PubMed
CDC. Newborn hepatitis B vaccination coverage among children born January 2003-June 2005—United States. MMWR Morb Mortal Wkly Rep 2008;57:825–8. PubMed
US Department of Health and Human Services, Office of Disease Prevention and Health Promotion. Healthy people 2020. Washington, DC: US Department of Health and Human Services; 2014. https://www.healthypeople.gov/
Walker TY, Elam-Evans LD, Singleton JA, et al. National, regional, state, and selected local area vaccination coverage among adolescents aged 13–17 years—United States, 2016. MMWR Morb Mortal Wkly Rep 2017;66:874–82. CrossRef PubMed
Williams WW, Lu PJ, O’Halloran A, et al. Surveillance of vaccination coverage among adult populations—United States, 2015. MMWR Surveill Summ 2017;66(No. SS-11):1–28. CrossRef PubMed
Agerton TB, Mahoney FJ, Polish LB, Shapiro CN. Impact of the bloodborne pathogens standard on vaccination of healthcare workers with hepatitis B vaccine. Infect Control Hosp Epidemiol 1995;16:287–91. CrossRef PubMed
Fan L, Owusu-Edusei K Jr, Schillie SF, Murphy TV. Cost-effectiveness of testing hepatitis B-positive pregnant women for hepatitis B e antigen or viral load. Obstet Gynecol 2014;123:929–37. CrossRef PubMed
CDC; The American College of Obstetricians and Gynecologists. Screening pregnant women for hepatitis B virus (HBV) infection. Atlanta, GA: US Department of Health and Human Services, CDC; 2015. https://www.cdc.gov/hepatitis/hbv/pdfs/prenatalhbsagtesting.pdf
Pan CQ, Duan ZP, Bhamidimarri KR, et al. An algorithm for risk assessment and intervention of mother to child transmission of hepatitis B virus. Clin Gastroenterol Hepatol 2012;10:452–9. CrossRef PubMed
Pan CQ, Han GR, Jiang HX, et al. Telbivudine prevents vertical transmission from HBeAg-positive women with chronic hepatitis B. Clin Gastroenterol Hepatol 2012;10:520–6. CrossRef PubMed
Chang JJ, Lewin SR. Immunopathogenesis of hepatitis B virus infection. Immunol Cell Biol 2007;85:16–23. CrossRef PubMed
Gish RG, Given BD, Lai CL, et al. Chronic hepatitis B: Virology, natural history, current management and a glimpse at future opportunities. Antiviral Res 2015;121:47–58. CrossRef PubMed
Hoofnagle JH, Di Bisceglie AM. Serologic diagnosis of acute and chronic viral hepatitis. Semin Liver Dis 1991;11:73–83. CrossRef PubMed
Krugman S, Overby LR, Mushahwar IK, Ling CM, Frösner GG, Deinhardt F. Viral hepatitis, type B. Studies on natural history and prevention re-examined. N Engl J Med 1979;300:101–6. CrossRef PubMed
Long SS, Prober CG, Fischer M. Principles and practice of pediatric infectious diseases. 5th ed. Amsterdam, the Netherlands: Elsevier; 2017.
Magnius LO, Norder H. Subtypes, genotypes and molecular epidemiology of the hepatitis B virus as reflected by sequence variability of the S-gene. Intervirology 1995;38:24–34. CrossRef PubMed
Kramvis A. Genotypes and genetic variability of hepatitis B virus. Intervirology 2014;57:141–50. CrossRef PubMed
Kramvis A. The clinical implications of hepatitis B virus genotypes and HBeAg in pediatrics. Rev Med Virol 2016;26:285–303. CrossRef PubMed
Allain JP. Occult hepatitis B virus infection. Transfus Clin Biol 2004;11:18–25. CrossRef PubMed
Trépo C, Chan HL, Lok A. Hepatitis B virus infection. Lancet 2014;384:2053–63. CrossRef PubMed
McMahon BJ, Alward WL, Hall DB, et al. Acute hepatitis B virus infection: relation of age to the clinical expression of disease and subsequent development of the carrier state. J Infect Dis 1985;151:599–603. CrossRef PubMed
Dienstag JL. Immunopathogenesis of the extrahepatic manifestations of hepatitis B virus infection. Springer Semin Immunopathol 1981;3:461–72. CrossRef PubMed
Beasley RP, Hwang LY, Lee GC, et al. Prevention of perinatally transmitted hepatitis B virus infections with hepatitis B immune globulin and hepatitis B vaccine. Lancet 1983;322:1099–102. CrossRef PubMed
Edmunds WJ, Medley GF, Nokes DJ, Hall AJ, Whittle HC. The influence of age on the development of the hepatitis B carrier state. Proc Biol Sci 1993;253:197–201. CrossRef PubMed
Hyams KC. Risks of chronicity following acute hepatitis B virus infection: a review. Clin Infect Dis 1995;20:992–1000. CrossRef PubMed
Hadler SC, Judson FN, O’Malley PM, et al. Outcome of hepatitis B virus infection in homosexual men and its relation to prior human immunodeficiency virus infection. J Infect Dis 1991;163:454–7. CrossRef PubMed
Beasley RP, Lin CC, Hwang LY, Chien CS. Hepatocellular carcinoma and hepatitis B virus. A prospective study of 22 707 men in Taiwan. Lancet 1981;318:1129–33. CrossRef PubMed
Goldstein ST, Zhou F, Hadler SC, Bell BP, Mast EE, Margolis HS. A mathematical model to estimate global hepatitis B disease burden and vaccination impact. Int J Epidemiol 2005;34:1329–39. CrossRef PubMed
McMahon BJ, Alberts SR, Wainwright RB, Bulkow L, Lanier AP. Hepatitis B-related sequelae. Prospective study in 1400 hepatitis B surface antigen-positive Alaska native carriers. Arch Intern Med 1990;150:1051–4. CrossRef PubMed
Jonas MM, Lok AS, McMahon BJ, et al. Antiviral therapy in management of chronic hepatitis B viral infection in children: a systematic review and meta-analysis. Hepatology 2016;63:307–18. CrossRef PubMed
Lok AS, McMahon BJ, Brown RS Jr, et al. Antiviral therapy for chronic hepatitis B viral infection in adults: A systematic review and meta-analysis. Hepatology 2016;63:284–306. CrossRef PubMed
McMahon BJ. Chronic hepatitis B virus infection. Med Clin North Am 2014;98:39–54. CrossRef PubMed
Wang C, Ji D, Chen J, et al. Hepatitis due to reactivation of hepatitis B virus in endemic areas among patients with hepatitis C treated with direct-acting antiviral agents. Clin Gastroenterol Hepatol 2017;15:132–6. CrossRef PubMed
Nelson NP, Jamieson DJ, Murphy TV. Prevention of perinatal hepatitis B virus transmission. J Pediatric Infect Dis Soc 2014;3(Suppl 1):S7–12. CrossRef PubMed
Schillie SF, Murphy TV. Seroprotection after recombinant hepatitis B vaccination among newborn infants: a review. Vaccine 2013;31:2506–16. CrossRef PubMed
Pondé RA. Atypical serological profiles in hepatitis B virus infection. Eur J Clin Microbiol Infect Dis 2013;32:461–76. >CrossRef PubMed
Pondé RA, Cardoso DD, Ferro MO. The underlying mechanisms for the ‘anti-HBc alone’ serological profile. Arch Virol 2010;155:149–58. CrossRef PubMed
Franks AL, Berg CJ, Kane MA, et al. Hepatitis B virus infection among children born in the United States to Southeast Asian refugees. N Engl J Med 1989;321:1301–5. CrossRef PubMed
Mortensen E, Kamali A, Schirmer PL, et al. Are current screening protocols for chronic hepatitis B virus infection adequate? Diagn Microbiol Infect Dis 2016;85:159–67. CrossRef PubMed
Calisti G, Herman O, Powley M, Haque T. Persistence of hepatitis B surface antigen in blood in a chronic haemodialysis patient following vaccination booster. BMJ Case Rep 2014;2014(jun10 1):bcr2013202191. CrossRef PubMed
Grob P, Jilg W, Bornhak H, et al. Serological pattern “anti-HBc alone”: report on a workshop. J Med Virol 2000;62:450–5. CrossRef PubMed
Silva AE, McMahon BJ, Parkinson AJ, Sjogren MH, Hoofnagle JH, Di Bisceglie AM. Hepatitis B virus DNA in persons with isolated antibody to hepatitis B core antigen who subsequently received hepatitis B vaccine. Clin Infect Dis 1998;26:895–7. CrossRef PubMed
Candotti D, Lin CK, Belkhiri D, et al. Occult hepatitis B infection in blood donors from South East Asia: molecular characterisation and potential mechanisms of occurrence. Gut 2012;61:1744–53. CrossRef PubMed
De Feo TM, Poli F, Mozzi F, Moretti MP, Scalamogna M; Collaborative Kidney, Liver and Heart North Italy Transplant Program Study Groups. Risk of transmission of hepatitis B virus from anti-HBC positive cadaveric organ donors: a collaborative study. Transplant Proc 2005;37:1238–9. CrossRef PubMed
Council of State and Territorial Epidemiologists. Hepatitis B, perinatal virus infection 2017 case definition. Atlanta, GA: Council of State and Territorial Epidemiologists; 2017. https://wwwn.cdc.gov/nndss/conditions/hepatitis-b-perinatal-virus-infection/case-definition/2017/
Nelson PK, Mathers BM, Cowie B, et al. Global epidemiology of hepatitis B and hepatitis C in people who inject drugs: results of systematic reviews. Lancet 2011;378:571–83. CrossRef PubMed
CDC. Viral hepatitis—CDC recommendations for specific populations and settings. Atlanta, GA: US Department of Health and Human Services, CDC; 2015. https://www.cdc.gov/hepatitis/populations/stds.htm
Hurie MB, Mast EE, Davis JP. Horizontal transmission of hepatitis B virus infection to United States-born children of Hmong refugees. Pediatrics 1992;89:269–73. PubMed
Chaudhary RK, Perry E, Cleary TE. Prevalence of hepatitis B infection among residents of an institution for the mentally retarded. Am J Epidemiol 1977;105:123–6. CrossRef PubMed
Thompson ND, Perz JF, Moorman AC, Holmberg SD. Nonhospital health care-associated hepatitis B and C virus transmission: United States, 1998-2008. Ann Intern Med 2009;150:33–9. CrossRef PubMed
Williams RE, Sena AC, Moorman AC, et al. Hepatitis B vaccination of susceptible elderly residents of long term care facilities during a hepatitis B outbreak. Vaccine 2012;30:3147–50. CrossRef PubMed
Woodruff BA, Vazquez E. Prevalence of hepatitis virus infections in an institution for persons with developmental disabilities. Am J Ment Retard 2002;107:278–92. CrossRef PubMed
Rosenberg SD, Goodman LA, Osher FC, et al. Prevalence of HIV, hepatitis B, and hepatitis C in people with severe mental illness. Am J Public Health 2001;91:31–7. CrossRef PubMed
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(No. RR-8):1–20. PubMed
Weinbaum C, Lyerla R, Margolis HS. Prevention and control of infections with hepatitis viruses in correctional settings. MMWR Recomm Rep 2003;52(No. RR-1):1–36, quiz CE1–4. PubMed
Dienstag JL, Ryan DM. Occupational exposure to hepatitis B virus in hospital personnel: infection or immunization? Am J Epidemiol 1982;115:26–39. CrossRef PubMed
Hadler SC, Doto IL, Maynard JE, et al. Occupational risk of hepatitis B infection in hospital workers. Infect Control 1985;6:24–31. CrossRef PubMed
US Department of Labor. Occupational Safety and Health Administration. OSHA Law and Regulations. https://www.osha.gov/law-regs.html
CDC. Recommendations for preventing transmission of infections among chronic hemodialysis patients. MMWR Recomm Rep 2001;50(No. RR-5):1–43. PubMed
Alter MJ, Favero MS, Maynard JE. Impact of infection control strategies on the incidence of dialysis-associated hepatitis in the United States. J Infect Dis 1986;153:1149–51. CrossRef PubMed
Finelli L, Miller JT, Tokars JI, Alter MJ, Arduino MJ. National surveillance of dialysis-associated diseases in the United States, 2002. Semin Dial 2005;18:52–61. CrossRef PubMed
Zibbell JE, Iqbal K, Patel RC, et al. Increases in hepatitis C virus infection related to injection drug use among persons aged =30 years—Kentucky, Tennessee, Virginia, and West Virginia, 2006–2012. MMWR Morb Mortal Wkly Rep 2015;64:453–8. PubMed
Bell BP. Hepatitis A and hepatitis B vaccination of patients with chronic liver disease. Acta Gastroenterol Belg 2000;63:359–63. PubMed
Johnson DF, Leder K, Torresi J. Hepatitis B and C infection in international travelers. J Travel Med 2013;20:194–202. CrossRef PubMed
Kellerman SE, Hanson DL, McNaghten AD, Fleming PL. Prevalence of chronic hepatitis B and incidence of acute hepatitis B infection in human immunodeficiency virus-infected subjects. J Infect Dis 2003;188:571–7. CrossRef PubMed
Chun HM, Fieberg AM, Hullsiek KH, et al. ; Infectious Disease Clinical Research Program HIV Working Group. Epidemiology of Hepatitis B virus infection in a US cohort of HIV-infected individuals during the past 20 years. Clin Infect Dis 2010;50:426–36. CrossRef PubMed
Homann C, Krogsgaard K, Pedersen C, Andersson P, Nielsen JO. High incidence of hepatitis B infection and evolution of chronic hepatitis B infection in patients with advanced HIV infection. J Acquir Immune Defic Syndr 1991;4:416–20. PubMed
Thio CL. Hepatitis B in the human immunodeficiency virus-infected patient: epidemiology, natural history, and treatment. Semin Liver Dis 2003;23:125–36. CrossRef PubMed
Alter MJ. Epidemiology of viral hepatitis and HIV co-infection. J Hepatol 2006;44(Suppl):S6–9. CrossRef PubMed
Thio CL, Seaberg EC, Skolasky R Jr, et al. ; Multicenter AIDS Cohort Study. HIV-1, hepatitis B virus, and risk of liver-related mortality in the Multicenter Cohort Study (MACS). Lancet 2002;360:1921–6. CrossRef PubMed
Reilly ML, Schillie SF, Smith E, et al. Increased risk of acute hepatitis B among adults with diagnosed diabetes mellitus. J Diabetes Sci Technol 2012;6:858–66. CrossRef PubMed
Schillie SF, Xing J, Murphy TV, Hu DJ. Prevalence of hepatitis B virus infection among persons with diagnosed diabetes mellitus in the United States, 1999–2010. J Viral Hepat 2012;19:674–6. CrossRef PubMed
Polish LB, Shapiro CN, Bauer F, et al. Nosocomial transmission of hepatitis B virus associated with the use of a spring-loaded finger-stick device. N Engl J Med 1992;326:721–5. CrossRef PubMed
Emini EA, Ellis RW, Miller WJ, McAleer WJ, Scolnick EM, Gerety RJ. Production and immunological analysis of recombinant hepatitis B vaccine. J Infect 1986;13(Suppl A):3–9. CrossRef PubMed
Stephenne J. Development and production aspects of a recombinant yeast-derived hepatitis B vaccine. Vaccine 1990;8(Suppl):S69–73, discussion S79–80.
CDC. Update: expanded availability of thimerosal preservative-free hepatitis B vaccine. MMWR Morb Mortal Wkly Rep 2000;49:642–51
US Food and Drug Administration. Licensed biological products with supporting documents. Silver Spring, MD: US Department of Health and Human Services, Food and Drug Administration; 2017. https://www.fda.gov/biologicsbloodvaccines/ucm133705.htm
Jack AD, Hall AJ, Maine N, Mendy M, Whittle HC. What level of hepatitis B antibody is protective? J Infect Dis 1999;179:489–92. CrossRef PubMed
Bruce MG, Bruden D, Hurlburt D, et al. Antibody levels and protection after hepatitis B vaccine: results of a 30-year follow-up study and response to a booster dose. J Infect Dis 2016;214:16–22. CrossRef PubMed
Leuridan E, Van Damme P. Hepatitis B and the need for a booster dose. Clin Infect Dis 2011;53:68–75. CrossRef PubMed
Simons BC, Spradling PR, Bruden DJ, et al. A longitudinal hepatitis B vaccine cohort demonstrates long-lasting hepatitis B virus (HBV) cellular immunity despite loss of antibody against HBV surface antigen. J Infect Dis 2016;214:273–80. CrossRef PubMed
André FE. Summary of safety and efficacy data on a yeast-derived hepatitis B vaccine. Am J Med 1989;87(3a):S14–20. CrossRef PubMed
Schillie SF, Spradling PR, Murphy TV. Immune response of hepatitis B vaccine among persons with diabetes: a systematic review of the literature. Diabetes Care 2012;35:2690–7. CrossRef PubMed
Averhoff F, Mahoney F, Coleman P, Schatz G, Hurwitz E, Margolis H. Immunogenicity of hepatitis B Vaccines. Implications for persons at occupational risk of hepatitis B virus infection. Am J Prev Med 1998;15:1–8. CrossRef PubMed
Shaw FE Jr, Guess HA, Roets JM, et al. Effect of anatomic injection site, age and smoking on the immune response to hepatitis B vaccination. Vaccine 1989;7:425–30. CrossRef PubMed
Bowman S, Grau LE, Singer M, Scott G, Heimer R. Factors associated with hepatitis B vaccine series completion in a randomized trial for injection drug users reached through syringe exchange programs in three US cities. BMC Public Health 2014;14:820. CrossRef PubMed
Drachman R, Isacsohn M, Rudensky B, Drukker A. Vaccination against hepatitis B in children and adolescent patients on dialysis. Nephrol Dial Transplant 1989;4:372–4. CrossRef PubMed
Lee C, Gong Y, Brok J, Boxall EH, Gluud C. Effect of hepatitis B immunisation in newborn infants of mothers positive for hepatitis B surface antigen: systematic review and meta-analysis. BMJ 2006;332:328–36. CrossRef PubMed
Patel DM, Butler J, Feldman S, Graves GR, Rhodes PG. Immunogenicity of hepatitis B vaccine in healthy very low birth weight infants. J Pediatr 1997;131:641–3. CrossRef PubMed
Marsano LS, West DJ, Chan I, et al. A two-dose hepatitis B vaccine regimen: proof of priming and memory responses in young adults. Vaccine 1998;16:624–9. CrossRef PubMed
Cassidy WM, Watson B, Ioli VA, Williams K, Bird S, West DJ. A randomized trial of alternative two- and three-dose hepatitis B vaccination regimens in adolescents: antibody responses, safety, and immunologic memory. Pediatrics 2001;107:626–31. CrossRef PubMed
Fabrizi F, Dixit V, Messa P, Martin P. Hepatitis B virus vaccine in chronic kidney disease: improved immunogenicity by adjuvants? A meta-analysis of randomized trials. Vaccine 2012;30:2295–300. CrossRef PubMed
Hovi L, Valle M, Siimes MA, Jalanko H, Saarinen UM. Impaired response to hepatitis B vaccine in children receiving anticancer chemotherapy. Pediatr Infect Dis J 1995;14:931–4. CrossRef PubMed
Zuin G, Principi N, Tornaghi R, et al. Impaired response to hepatitis B vaccine in HIV infected children. Vaccine 1992;10:857–60. CrossRef PubMed
World Health Organization. Information sheet observed rate of vaccine reactions: hepatitis B vaccine. Geneva, Switzerland: World Health Organization; 2012. http://www.who.int/vaccine_safety/initiative/tools/Hep_B_Vaccine_rates_information_sheet.pdf
Bohlke K, Davis RL, Marcy SM, et al. ; Vaccine Safety Datalink Team. Risk of anaphylaxis after vaccination of children and adolescents. Pediatrics 2003;112:815–20. CrossRef PubMed
Stratton K, Ford A, Rusch E, Clayton EW, eds. Adverse effects of vaccines: evidence and causality. Washington, DC: National Academy Press; 2012.
Stratton K, Almario D, McCormick MC, editors. Immunization safety review: hepatitis B vaccine and demyelinating neurological disorders. Washington, DC: National Academies Press; 2002.
Halsey NA, Duclos P, Van Damme P, Margolis H; Viral Hepatitis Prevention Board. Hepatitis B vaccine and central nervous system demyelinating diseases. Pediatr Infect Dis J 1999;18:23–4. CrossRef PubMed
DeStefano F, Weintraub ES, Chen RT. Hepatitis B vaccine and risk of multiple sclerosis. Pharmacoepidemiol Drug Saf 2007;16:705–7, author reply 707–8. CrossRef PubMed
Ray P, Black S, Shinefield H, et al. ; Vaccine Safety Datalink Team. Risk of rheumatoid arthritis following vaccination with tetanus, influenza and hepatitis B vaccines among persons 15–59 years of age. Vaccine 2011;29:6592–7. CrossRef PubMed
Rowhani-Rahbar A, Klein NP, Lewis N, et al. Immunization and Bell’s palsy in children: a case-centered analysis. Am J Epidemiol 2012;175:878–85. CrossRef PubMed
Yu O, Bohlke K, Hanson CA, et al. Hepatitis B vaccine and risk of autoimmune thyroid disease: a Vaccine Safety Datalink study. Pharmacoepidemiol Drug Saf 2007;16:736–45. CrossRef PubMed
Naleway AL, Belongia EA, Donahue JG, Kieke BA, Glanz JM; Vaccine Safety Datalink. Risk of immune hemolytic anemia in children following immunization. Vaccine 2009;27:7394–7. CrossRef PubMed
McNeil MM, Weintraub ES, Duffy J, et al. Risk of anaphylaxis after vaccination in children and adults. J Allergy Clin Immunol 2016;137:868–78. CrossRef PubMed
Baxter R, Lewis E, Fireman B, DeStefano F, Gee J, Klein NP. Case-centered analysis of optic neuritis after vaccines. Clin Infect Dis 2016;63:79–81. CrossRef PubMed
Baxter R, Bakshi N, Fireman B, et al. Lack of association of Guillain-Barré syndrome with vaccinations. Clin Infect Dis 2013;57:197–204. CrossRef PubMed
Baxter R, Lewis N, Bohrer P, Harrington T, Aukes L, Klein NP. Sudden-onset sensorineural hearing loss after immunization: a case-centered analysis. Otolaryngol Head Neck Surg 2016;155:81–6. CrossRef PubMed
138.Haber P, Moro PL, Ng C, et al. Safety of currently licensed hepatitis B surface antigen vaccines in the United States, Vaccine adverse event reporting system (VAERS), 2005–2015. Vaccine 2017. http://www.sciencedirect.com/science/article/pii/S0264410X1731722X
Hadler SC, de Monzon MA, Lugo DR, Perez M. Effect of timing of hepatitis B vaccine doses on response to vaccine in Yucpa Indians. Vaccine 1989;7:106–10. CrossRef PubMed
Halsey NA, Moulton LH, O’Donovan JC, et al. Hepatitis B vaccine administered to children and adolescents at yearly intervals. Pediatrics 1999;103:1243–7. CrossRef PubMed
Wiström J, Ahlm C, Lundberg S, Settergren B, Tärnvik A. Booster vaccination with recombinant hepatitis B vaccine four years after priming with one single dose. Vaccine 1999;17:2162–5. CrossRef PubMed
Jilg W, Schmidt M, Deinhardt F. Vaccination against hepatitis B: comparison of three different vaccination schedules. J Infect Dis 1989;160:766–9. CrossRef PubMed
Tan KL, Goh KT, Oon CJ, Chan SH. Immunogenicity of recombinant yeast-derived hepatitis B vaccine in nonresponders to perinatal immunization. JAMA 1994;271:859–61. CrossRef PubMed
Brown RS Jr, McMahon BJ, Lok AS, et al. Antiviral therapy in chronic hepatitis B viral infection during pregnancy: A systematic review and meta-analysis. Hepatology 2016;63:319–33. CrossRef PubMed
Jourdain G, Ngo-Giang-Huong N, Cressey TR, et al. Prevention of mother-to-child transmission of hepatitis B virus: a phase III, placebo-controlled, double-blind, randomized clinical trial to assess the efficacy and safety of a short course of tenofovir disoproxil fumarate in women with hepatitis B virus e-antigen. BMC Infect Dis 2016;16:393. CrossRef PubMed
Han GR, Jiang HX, Yue X, et al. Efficacy and safety of telbivudine treatment: an open-label, prospective study in pregnant women for the prevention of perinatal transmission of hepatitis B virus infection. J Viral Hepat 2015;22:754–62. CrossRef PubMed
Fan L, Owusu-Edusei K Jr, Schillie SF, Murphy TV. Cost-effectiveness of active-passive prophylaxis and antiviral prophylaxis during pregnancy to prevent perinatal hepatitis B virus infection. Hepatology 2016;63:1471–80. CrossRef PubMed
Barbosa C, Smith EA, Hoerger TJ, et al. Cost-effectiveness analysis of the national Perinatal Hepatitis B Prevention Program. Pediatrics 2014;133:243–53. CrossRef PubMed
Hoerger TJ, Schillie S, Wittenborn JS, et al. Cost-effectiveness of hepatitis B vaccination in adults with diagnosed diabetes. Diabetes Care 2013;36:63–9. CrossRef PubMed
Hoerger TJ, Bradley C, Schillie SF, Reilly M, Murphy TV. Cost-effectiveness of ensuring hepatitis B protection for previously vaccinated healthcare personnel. Infect Control Hosp Epidemiol 2014;35:845–54. CrossRef PubMed
CDC. General recommendations on immunization—recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Recomm Rep 2011;60(No. RR-2):1–64. PubMed

CME / ABIM MOC / CE

Prevention of Hepatitis B Virus Infection in the United States: Recommendations of the Advisory Committee on Immunization Practices

Authors: Sarah Schillie, MD; Claudia Vellozzi, MD; Arthur Reingold, MD; Aaron M. Harris, MD; Penina Haber, MPH; John W. Ward, MD; Noele P. Nelson, MD
CME / ABIM MOC / CE Released: 3/12/2018
THIS ACTIVITY HAS EXPIRED FOR CREDIT
Valid for credit through: 3/12/2019, 11:59 PM EST

Start Activity

Target Audience and Goal Statement

This activity is intended for infectious disease specialists, family medicine specialists, gastroenterologists, internists, nephrologists, obstetrician-gynecologists, pediatricians, public health officials, nurses, pharmacists, and other clinicians caring for patients with or at risk for hepatitis B virus (HBV) infection.

Describe recommendations regarding prevention of HBV infection in the United States, based on updated guidance from the Advisory Committee on Immunization Practices.

Upon completion of this activity, participants will be able to:

Discuss new or updated recommendations regarding prevention of hepatitis B virus (HBV) infection in the United States, based on updated guidance from the Advisory Committee on Immunization Practices (ACIP)
Identify previously issued ACIP recommendations regarding prevention of HBV infection in the United States, including recommendations for HBV vaccination of infants, children, and adolescents
Describe ACIP/Centers for Disease Control and Prevention recommendations for HBV prophylaxis after occupational and nonoccupational exposures

Disclosures

As an organization accredited by the ACCME, Medscape, LLC, requires everyone who is in a position to control the content of an education activity to disclose all relevant financial relationships with any commercial interest. The ACCME defines "relevant financial relationships" as financial relationships in any amount, occurring within the past 12 months, including financial relationships of a spouse or life partner, that could create a conflict of interest.

Medscape, LLC, encourages Authors to identify investigational products or off-label uses of products regulated by the US Food and Drug Administration, at first mention and where appropriate in the content.

Author(s)

Sarah Schillie, MD

Division of Viral Hepatitis, National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention, Centers for Disease Control and Prevention, Atlanta, Georgia

Disclosures

Disclosure: Sarah Schillie, MD, has disclosed no relevant financial relationships.

Claudia Vellozzi, MD

Division of Viral Hepatitis, National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention, Centers for Disease Control and Prevention, Atlanta, Georgia

Disclosures

Disclosure: Claudia Vellozzi, MD, has disclosed no relevant financial relationships.

Arthur Reingold, MD

University of California, Berkeley School of Public Health, Berkeley, California

Disclosures

Disclosure: Arthur Reingold, MD, has disclosed no relevant financial relationships.

Aaron M. Harris, MD

Division of Viral Hepatitis, National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention, Centers for Disease Control and Prevention, Atlanta, Georgia

Disclosures

Disclosure: Aaron M. Harris, MD, has disclosed no relevant financial relationships.

Penina Haber, MPH

Division of Healthcare Quality Promotion, National Center for Emerging and Zoonotic Infectious Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia

Disclosures

Disclosure: Penina Haber, MPH, has disclosed no relevant financial relationships.

John W. Ward, MD

Division of Viral Hepatitis, National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention, Centers for Disease Control and Prevention, Atlanta, Georgia

Disclosures

Disclosure: John W. Ward, MD, has disclosed no relevant financial relationships.

Noele P. Nelson, MD

Division of Viral Hepatitis, National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention, Centers for Disease Control and Prevention, Atlanta, Georgia

Disclosures

Disclosure: Noele P. Nelson, MD, has disclosed no relevant financial relationships.

CME Author

Laurie Barclay, MD

Freelance writer and reviewer, Medscape, LLC

Disclosures

Disclosure: Laurie Barclay, MD, has disclosed the following relevant financial relationships:
Owns stock, stock options, or bonds from: Pfizer

CME Reviewer/Nurse Planner

Amy Bernard, MS, BSN, RN-BC

Lead Nurse Planner, Medscape, LLC

Disclosures

Disclosure: Amy Bernard, MS, BSN, RN-BC, has disclosed no relevant financial relationships.

Accreditation Statements

In support of improving patient care, Medscape, LLC is jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team.

For Physicians

Medscape, LLC designates this enduring material for a maximum of 2.5 AMA PRA Category 1 Credit(s)™ . Physicians should claim only the credit commensurate with the extent of their participation in the activity.

Medscape, LLC staff have disclosed that they have no relevant financial relationships.

Successful completion of this CME activity, which includes participation in the evaluation component, enables the participant to earn up to 2.5 MOC points in the American Board of Internal Medicine's (ABIM) Maintenance of Certification (MOC) program. Participants will earn MOC points equivalent to the amount of CME credits claimed for the activity. It is the CME activity provider's responsibility to submit participant completion information to ACCME for the purpose of granting ABIM MOC credit. Aggregate participant data will be shared with commercial supporters of this activity.

Contact This Provider

For Nurses

Awarded 2.5 contact hour(s) of continuing nursing education for RNs and APNs; 2.5 contact hours are in the area of pharmacology.

Contact This Provider

For Pharmacists

Medscape, LLC designates this continuing education activity for 2.5 contact hour(s) (0.250 CEUs) (Universal Activity Number JA0007105-0000-18-022-H01-P).

Contact This Provider

For questions regarding the content of this activity, contact the accredited provider for this CME/CE activity noted above. For technical assistance, contact [email protected]

Instructions for Participation and Credit

There are no fees for participating in or receiving credit for this online educational activity. For information on applicability and acceptance of continuing education credit for this activity, please consult your professional licensing board.

This activity is designed to be completed within the time designated on the title page; physicians should claim only those credits that reflect the time actually spent in the activity. To successfully earn credit, participants must complete the activity online during the valid credit period that is noted on the title page. To receive AMA PRA Category 1 Credit™, you must receive a minimum score of 75% on the post-test.

Follow these steps to earn CME/CE credit*:

Read the target audience, learning objectives, and author disclosures.
Study the educational content online or printed out.
Online, choose the best answer to each test question. To receive a certificate, you must receive a passing score as designated at the top of the test. We encourage you to complete the Activity Evaluation to provide feedback for future programming.

You may now view or print the certificate from your CME/CE Tracker. You may print the certificate but you cannot alter it. Credits will be tallied in your CME/CE Tracker and archived for 6 years; at any point within this time period you can print out the tally as well as the certificates from the CME/CE Tracker.

*The credit that you receive is based on your user profile.

processing....

Prophylaxis Against HBV Infection

Hepatitis B Vaccines and Hepatitis B Immune Globulins

HepB vaccination is the mainstay of HBV prevention efforts; HBIG is generally used as an adjunct to HepB vaccine in infants born to HBsAg-positive mothers and in certain other postexposure prophylaxis situations. The first HepB vaccines consisted of plasma-derived HBsAg. Recombinant HepB vaccines containing yeast-derived HBsAg purified by biochemical and biophysical separation techniques replaced the plasma-derived vaccines in the United States by the late 1980s.^[64,103,104] HepB vaccines recommended for use in the United States are formulated to contain 10–40 µg of HBsAg protein/mL and do not contain thimerosal as a preservative.^[105] HBIG can augment protection until a response to vaccination is attained. For those who do not respond to HepB vaccination, HBIG administered alone is the primary means of protection after an HBV exposure. HBIG provides passively acquired anti-HBs and temporary protection (i.e., 3–6 months). Passively acquired anti-HBs can be detected for 4–6 months after administration of HBIG.^[10]

HepB vaccines are available as a single-antigen formulation and in combination with other vaccines. The two single-antigen vaccines recommended for use in the United States, Engerix-B (GlaxoSmithKline Biologicals, Rixensart, Belgium) and Recombivax HB (Merck & Co., Inc., Whitehouse Station, New Jersey), are used for the vaccination of persons starting at birth. Of the two combination vaccines, Pediarix (GlaxoSmithKline Biologicals, Rixensart, Belgium) is used for the vaccination of persons aged 6 weeks–6 years and contains recombinant HBsAg, diphtheria and tetanus toxoids and acellular pertussis adsorbed, and inactivated poliovirus and Twinrix (GlaxoSmithKline Biologicals, Rixensart, Belgium) is used for the vaccination of persons aged ≥18 years and contains recombinant HBsAg and inactivated hepatitis A virus ( Table 2 ). Comvax (Merck & Co., Inc., Whitehouse Station, New Jersey), which was used previously for the vaccination of persons aged 6 weeks–15 months and contained recombinant HBsAg and Haemophilus b conjugate vaccine, has not been available for purchase directly from Merck since January 1, 2015. Discontinuation of Comvax was not related to any product safety or manufacturing issues. Aluminum salts generally are used as adjuvants to enhance the immune response of vaccinated persons.

Two HBIG products are licensed for use in the United States: HepaGam B (Cangene Corporation, Winnipeg, Canada) and Nabi-HB (Biotest Pharmaceuticals Corporation, Boca Raton, Florida). HBIG is prepared from the plasma of donors with high concentrations of anti-HBs. Source plasma tests negative for evidence of HIV, HBV, and HCV. Investigational nucleic acid testing for hepatitis A virus and parvovirus B19 also is performed on pooled samples of source plasma. The manufacturing process contains two steps to inactivate viruses in the final product: the solvent and detergent step inactivates enveloped viruses, and the virus filtration step removes viruses based on their size. HBIG products licensed for use in the United States contain no preservative and are intended for single use only.^[106]

Vaccine-Induced Seroprotection

The presence of anti-HBs typically indicates immunity against HBV infection. Immunocompetent children and adults who have vaccine-induced anti-HBs levels of ≥10 mIU/mL 1–2 months after having received a complete HepB vaccine series are considered seroprotected and deemed vaccine responders.^[107] Vaccine-induced seroprotection is considered a surrogate of clinical protection. Anti-HBs levels wane over time following vaccination related in part to the age at vaccination. Approximately 16% of persons vaccinated at age <1 year have antibody levels of ≥10 mIU/mL 18 years following vaccination, compared with 74% for those vaccinated at age ≥1 year.^[10] However, persons initially responding to the full 3-dose HepB vaccine series and who are later found to have anti-HBs <10 mIU/mL remain protected. Most persons (88%) who receive a challenge dose of HepB vaccine 30 years after HepB vaccination as children or adults develop an antibody response of ≥10 mIU/mL indicating persistent immunity to HBV infection.^[108] Data from this and other studies suggests protection against acute symptomatic and chronic HBV infection persists for 30 years or more among immunocompetent persons who originally responded to HepB vaccine.^[108-110]

The 3-dose HepB vaccine series produces a protective antibody response (anti-HBs ≥10 mIU/mL) in approximately 95% of healthy infants overall (response is lower for infants with lower birth weights)^[64] and >90% of healthy adults aged <40 years.^[111,112] Among healthy infants, 25% and 63% achieve anti-HBs levels ≥10 mIU/mL after the first and second dose, respectively. Among healthy adults aged <40 years, 30%–55% and 75% achieve anti-HBs levels ≥10 mIU/mL after the first and second dose, respectively.^[7,8,64] Vaccine response is decreased among infants weighing <2000 grams and older adults. Other factors (e.g., smoking, obesity, aging, chronic medical conditions, drug use, diabetes, male sex, genetic factors, and immune suppression) contribute to a decreased response to vaccine.^[113-116] Although immunogenicity is lower among immunocompromised persons, those who achieve and maintain seroprotective antibody levels before exposure to HBV have a high level of protection.^[8]

Birth dose. A birth dose of HepB vaccine serves as postexposure prophylaxis to prevent perinatal HBV infection among infants born to HBV-infected mothers. Although infants requiring postexposure prophylaxis should be identified by maternal HBsAg testing, administration of a birth dose to all infants (even without HBIG) serves as a safeguard to prevent perinatal transmission among infants born to HBsAg-positive mothers not identified prenatally because of lack of maternal HBsAg testing or failures in reporting test results. HepB vaccine or HBIG given alone are 75% and 71% effective in preventing perinatal HBV transmission, respectively; their combined efficacy is 94%.^[29,52,117] The birth dose also provides protection to infants at risk from household exposure after the perinatal period.^[29,64]

Vaccination produces seroprotection in 98% of healthy term infants. Vaccine response is lower among infants with birth weights <2000 grams.^[64] A study among low birth weight infants demonstrated that more infants achieved seroprotective anti-HBs levels when vaccine was initiated at 1 month of age versus within the first 3 days of life (96% vs. 68%, p<0.02).^[118] Vaccine response among infants does not vary appreciably by maternal HBsAg status or HBIG administration.^[64]

Adolescents. Approximately 95% of adolescents achieve seroprotection following HepB vaccination with a complete series.^[7] The adult (10 µg) dose of Recombivax HB administered using a 2-dose compressed schedule at 0 and 4 months or 0 and 6 months for persons aged 11–15 years produces seroprotection proportions nearly equivalent to those obtained with the standard regimen of 5 µg administered on a 3-dose schedule at 0, 1, and 6 months (99.2% vs. 98.3%).^[119,120] Data on long-term antibody persistence or protection among adolescents for 2-dose schedules are lacking.

Adults. Vaccination with a complete series results in seroprotection in >90% of healthy adults aged <40 years. Response decreases with age, and seroprotection is achieved in 75% of persons aged 60 years.^[8]

Diabetes. A review of studies assessing HepB vaccine response among persons with diabetes mellitus demonstrated seroprotection in 93.9% for children with diabetes mellitus compared with 100% for children without diabetes mellitus.^[112,121]

Among adults, 88.2% of those with diabetes mellitus, compared with 93.6% of those without diabetes mellitus, achieved seroprotection.^[112] Among hemodialysis/chronic kidney disease patients, the median proportion protected was 60.1% for those with diabetes mellitus, compared with 75.1% for those without diabetes mellitus.^[112]

Immunocompromising conditions. The humoral response to HepB vaccine is reduced in children and adults who are immunocompromised (e.g., hematopoietic stem cell transplant recipients, patients undergoing chemotherapy, and HIV-infected persons).^[122,123] Modified dosing regimens, including a doubling of the standard antigen dose or administration of additional doses, might increase response rates. However, data on response to these alternative vaccination schedules are limited.^[6]

Vaccine Safety

In prelicensure trials, adverse events following HepB vaccination were most commonly injection site reactions and mild systemic reactions.^[106] Commonly reported mild adverse events from postmarketing data include pain (3%–29%), erythema (3%), swelling (3%), fever (1%–6%), and headache (3%).^[124] The estimated incidence of anaphylaxis among HepB vaccine recipients is 1.1 per million vaccine doses.^[125] In 2011, the Institute of Medicine concluded that the evidence convincingly supports a causal relationship between HepB vaccine and anaphylaxis in yeast-sensitive persons, and that the evidence is inadequate to accept or reject a causal relation between HepB vaccine and several neurologic, chronic, and autoimmune diseases.^[126]

During early postlicensure surveillance, several adverse events following HepB vaccination have been described in the scientific literature, including Guillain-Barré Syndrome (GBS), chronic fatigue syndrome, optic neuritis, multiple sclerosis, and diabetes mellitus; however, multiple studies have demonstrated no association between receipt of HepB vaccine and these conditions.^[126-129] In addition, no evidence of a causal association between rheumatoid arthritis,^[130] Bell’s palsy,^[131] autoimmune thyroid disease,^[132] hemolytic anemia in children,^[133] anaphylaxis,^[134] optic neuritis,^[135] Guillain-Barré Syndrome,^[136] sudden-onset sensorineural hearing loss,^[137] or other chronic illnesses and receipt of HepB vaccine has been demonstrated through analysis of VSD data.

During 2005–2015, a total of 20,231 reports of adverse events following HepB vaccination among all ages were submitted to VAERS. The majority of primary U.S. reports (15,787 of 20,231, 78%) were following HepB vaccine administered with other vaccines on the same visit. Among these, the percentage classified as serious (i.e., if one or more of the following is reported: death, life-threatening illness, hospitalization or prolongation of existing hospitalization, or permanent disability)^† was 16.7%, including 402 deaths, of which 388 were among infants aged 6 weeks–23 months.^[138] The most frequently reported adverse events for vaccines given in combination were fever (23%), injection site erythema (11%), and vomiting (10%).^[138] Among the 4,444 single-antigen HepB reports, 6.5% were classified as serious, including 43 deaths, of which 27 were among infants aged ≤4 weeks. The most frequently reported adverse events for single-antigen HepB vaccine were nausea/dizziness (8%) and fever/headache (7%).

Vaccination Schedules

Vaccine schedules are determined on the basis of immunogenicity data, and, for infants and children, the need to integrate HepB vaccine into a harmonized immunization schedule ( Table 3 and Table 4 ). Primary vaccination generally consists of three intramuscular doses administered on a 0-, 1-, and 6-month schedule ( Table 4 ). Recombivax HB may be administered in a 2-dose schedule at 0 and 4–6 months for persons aged 11–15 years using the adult formulation. Pediarix is administered at ages 2, 4, and 6 months; it is not used for the birth dose. Twinrix may be administered before travel or any other potential exposure on an accelerated schedule at 0, 7, and 21–30 days, followed by a dose at 12 months. HepB vaccination of adult hemodialysis patients consists of high-dose (40 µg) Recombivax HB administered on a 0-, 1-, and 6-month schedule or high-dose (40 µg) Engerix-B administered on a 0-, 1-, 2-, and 6-month schedule.^[106]

Alternative vaccination schedules (e.g., 0, 1, and 4 months or 0, 2, and 4 months) have been demonstrated to elicit dose-specific and final rates of seroprotection similar to those obtained on a 0-, 1-, and 6-month schedule. Increasing the interval between the first 2 doses has little effect on immunogenicity or the final antibody concentration.^[139-141] The third dose confers the maximum level of seroprotection and provides long-term protection.^[142] Longer intervals between the last 2 doses (e.g., 11 months) result in higher final antibody levels^[142] but might increase the risk for acquisition of HBV infection among persons who have a delayed response to vaccination. Higher geometric mean titers are associated with longer persistence of measurable anti-HBs.

Response to Revaccination

A challenge dose of HepB vaccine may be used to determine the presence of vaccine-induced immunologic memory through generation of an anamnestic response. The term “booster dose” has been used to refer to a dose of HepB vaccine administered after a primary vaccination series to provide rapid protective immunity against significant infection (i.e., infection resulting in serologic test results positive for HBV and/or clinically significant disease). Among persons who were vaccinated prior to age 1 year and found to have anti-HBs levels <10 mIU/mL 6–18 years later, a single challenge dose of HepB vaccine resulted in anti-HBs levels ≥10 mIU/mL in 60%–97% of those tested. Similar results were found among persons initially vaccinated at age ≥1 year.^[10] Immunocompetent persons with a response ≥10 mIU/mL following a challenge dose are considered protected, regardless of subsequent declines in anti-HBs.^[10,109]

One study found that of infants born to HBsAg-positive women who were not infected at birth and who did not respond to a primary vaccine series, all developed seroprotective levels of anti-HBs after receipt of 3 additional doses.^[143] No data exist that suggest that children who have no detectable antibody after 6 doses of vaccine benefit from additional doses.

Maternal Antiviral Therapy for Preventing Perinatal HBV Transmission

Antiviral therapy (i.e., lamivudine, telbivudine, and tenofovir) has been studied as an intervention to reduce perinatal HBV transmission among pregnant women with high HBV DNA levels (e.g., average HBV DNA levels of 7.6 log10 IU/mL).^[144] Maternal antiviral therapy started at 28–32 weeks’ gestation, as an adjunct to HepB vaccine and HBIG administered to the infant shortly after delivery, has been associated with significantly reduced rates of perinatal HBV transmission.^[5] The use of lamivudine and telbivudine is limited by viral resistance and mutations. Tenofovir is not associated with resistance and is the preferred agent.^[5] Available data support the safety of tenofovir during pregnancy, although its use might be associated with reduced bone mineral content in infants with in utero exposure.^{[5,39,63,144-146]} AASLD suggests antiviral therapy to reduce perinatal HBV transmission when maternal HBV DNA is >200,000 IU/mL. Maternal therapy is generally discontinued at birth to 3 months postpartum.^[5]

Cost-Effectiveness Considerations

HBV prevention strategies targeting perinatal transmission are considered very cost-effective (i.e., an incremental cost-effectiveness ratio <$25,000). The current strategy of administering HepB vaccine and HBIG within 12 hours of birth for infants born to HBsAg-positive mothers and universal infant vaccination prior to hospital discharge has an incremental cost-effectiveness ratio of $6,957 per quality-adjusted life year (QALY) saved when compared with a strategy of universal infant HepB vaccination prior to hospital discharge alone.^[147] CDC’s U.S. Perinatal Hepatitis B Prevention Program (https://www.cdc.gov/hepatitis/partners/perihepbcoord.htm), which provides case management services to infants born to HBsAg-positive women, also has been demonstrated to decrease infections, increase QALYs saved, and be a cost-effective use of resources.^[148] A strategy of testing HBsAg-positive pregnant women for HBV DNA, followed by maternal antiviral prophylaxis for women with high HBV DNA, would cost an additional $3 million but would save 2,080 QALYs and prevent 324 chronic HBV infections, and therefore would be considered cost-effective, with an incremental cost-effectiveness ratio of $1,583 per QALY saved.^[36]

Cost-effectiveness also has been assessed for HBV prevention strategies outside of the perinatal setting. Vaccinating adults aged 20–59 years with diabetes mellitus costs $75,094 per QALY saved; cost-effectiveness ratios increase with age at vaccination.^[149] Among previously vaccinated current HCP (including those in training), pre-exposure anti-HBs testing followed by revaccination and retesting (if necessary, based on anti-HBs levels), compared with no intervention, was not considered cost-effective with an incremental cost per QALY saved of $3–$4 million at year one and approximately $800,000 over 10 years.^[150]

« Back

Page 6 of 12

Recommendations

CME / ABIM MOC / CE Information

Summary
Introduction
New or Updated Recommendations
Methods
HBV Background
Prophylaxis Against HBV Infection
Recommendations
Persons Recommended for HepB Vaccination
Implementation Strategies
Postexposure Prophylaxis
Immunization Management Issues
Future Directions

References

Table 1.

Table 2.

Table 3.

Table 4.

Table 5.

Table 6.

Box 1.

Box 2.

Box 3.

Box 4.

Box 5.

Box 6.

Box 7.

References

Faculty and Disclosures

Author(s)

Sarah Schillie, MD

Claudia Vellozzi, MD

Arthur Reingold, MD

Aaron M. Harris, MD

Penina Haber, MPH

John W. Ward, MD

Noele P. Nelson, MD

CME Author

Laurie Barclay, MD

CME Reviewer/Nurse Planner

Amy Bernard, MS, BSN, RN-BC

CME / ABIM MOC / CE

Prevention of Hepatitis B Virus Infection in the United States: Recommendations of the Advisory Committee on Immunization Practices

Target Audience and Goal Statement

Disclosures

Author(s)

Sarah Schillie, MD

Claudia Vellozzi, MD

Arthur Reingold, MD

Aaron M. Harris, MD

Penina Haber, MPH

John W. Ward, MD

Noele P. Nelson, MD

CME Author

Laurie Barclay, MD

CME Reviewer/Nurse Planner

Amy Bernard, MS, BSN, RN-BC

Accreditation Statements

For Physicians

For Nurses

For Pharmacists

Instructions for Participation and Credit

Prevention of Hepatitis B Virus Infection in the United States: Recommendations of the Advisory Committee on Immunization Practices: Prophylaxis Against HBV Infection

Prophylaxis Against HBV Infection

Hepatitis B Vaccines and Hepatitis B Immune Globulins

Vaccine-Induced Seroprotection

Vaccine Safety

Vaccination Schedules

Response to Revaccination

Maternal Antiviral Therapy for Preventing Perinatal HBV Transmission

Cost-Effectiveness Considerations

Table of Contents