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.

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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

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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.

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HBV Background

Epidemiology

In 2015, a total of 3,370 cases of acute HBV infection were reported to CDC. The actual number of acute cases is believed to be 6.5 times the number of reported cases in any year. It is estimated that 21,900 new cases of HBV occurred in 2015 after under-ascertainment and under-reporting were considered.^[4] The rate of reported acute HBV infections declined 88.5% since recommendations for HepB vaccination were first issued, from 9.6 cases per 100,000 population in 1982 to 1.1 cases per 100,000 population in 2015,^[15] although the rate of acute HBV infections remained fairly stable during 2010–2015^[4] (Figure 1). The 2015 incidence is greatest for persons aged 30–39 years (2.6 per 100,000 population). In 2015, persons aged =19 years had the lowest incidence (0.02 cases per 100,000 population), likely a result of routine infant vaccination. Although the incidence of acute HBV infection is greater for males than for females, the gap has narrowed; in 2015, the rate for males was approximately 1.6 times higher than that for females (1.3 cases and 0.8 cases per 100,000 population, respectively).^[4] During 2009–2013, the combined incidence of acute HBV infection in three states (Kentucky, Tennessee, and West Virginia) increased 114% and was associated with increasing injection-drug use.^[16]

Enlarge

Figure 1. Incidence of hepatitis B virus infection — National Notifiable Diseases Surveillance System, United States, 1980–2015

On the basis of national health survey data, it is estimated that approximately 850,000 persons are living with HBV infection (prevalence) in the United States.^[17,18] Studies based on data from countries of persons migrating to the United States and census data indicate that the total prevalence of chronic hepatitis B might be as high as 2.2 million persons,^[19] suggesting that the national health survey-based estimate might be conservative. Foreign-born persons account for approximately 95% of newly reported chronic infections in the United States^[20]; the prevalence of chronic HBV infection is approximately 3.5% among foreign-born persons,^[19] and the majority of chronic HBV infections in the United States are among Asians/Pacific Islanders.

Strategy to Eliminate HBV

In 1991, the United States adopted a strategy for universal HepB vaccination of infants.^[21] A comprehensive strategy to eliminate HBV transmission evolved over the ensuing 3 decades and encompasses 1) routine testing of all pregnant women for HBsAg and prophylaxis for infants born to HBsAg-positive mothers, 2) universal vaccination of infants beginning at birth, 3) routine vaccination of previously unvaccinated children and adolescents, and 4) vaccination of adults at risk for HBV infection.^[7-11,21-26] Preventing perinatal transmission relies upon testing all pregnant women for HBsAg and administering timely prophylaxis (HepB vaccine and hepatitis B immune globulin [HBIG]) to infants born to infected mothers. Universal HepB vaccination of all infants beginning at birth provides a critical safeguard and prevents infection among infants born to HBsAg-positive mothers not identified prenatally (e.g., in situations where the mother was not tested or when testing, interpretation, or transcription errors occurred). Vaccination of children and adolescents not previously vaccinated and vaccination of adults at risk for HBV infection (e.g., by sexual or percutaneous exposure and international travelers to certain countries) is recommended to prevent HBV transmission outside of the perinatal setting ( Box 2 ).

HBV prevention strategies have been implemented successfully in the United States, but challenges remain. Approximately 88% of commercially insured women and 84% of Medicaid-enrolled women are tested for HBsAg during pregnancy.^[27] In one study of a large health system in northern California, 93% of HBsAg-positive pregnant women were tested for HBV DNA.^[28] Most (94.9%) infants born to infected women receive recommended prophylaxis within 12 hours of birth.^[29] Universal HepB vaccine birth dose coverage, defined as 1 dose of vaccine administered by 3 days of life, is 71.1%,^[30] an increase from 50.1% during 2003–2005 prior to revised ACIP recommendations for the birth dose before hospital discharge,^[31] but below the Healthy People 2020 target of 85%.^[32] HepB vaccine coverage (≥3 doses) among children aged 19–35 months and 13–17 years is 90.5%^[30] and 91.4%,^[33] respectively. Vaccine coverage (≥3 doses) is lower among adults: 27.4% among adults who report chronic liver conditions; 31.6% among adults who traveled outside the United States to countries other than Europe, Japan, Australia, New Zealand, or Canada since 1995; and 24.4% among adults with diabetes aged 19–59 years and 12.6% of adults with diabetes aged ≥60 years.^[34] Among health care personnel (HCP), ≥3-dose coverage was 64.7%, an increase from 51% in 1992 shortly after implementation of the Needlestick Safety and Prevention Act,^[35] but well below the Healthy People 2020 target of 90%.^[32,34]

New strategies for further reducing HBV transmission in this report include testing HBsAg-positive pregnant women for HBV DNA to identify infants at greatest risk for infection and guide the use of maternal antiviral therapy.^[36,37] Published evidence indicates that maternal antiviral therapy during pregnancy further reduces perinatal HBV transmission; hence, AASLD suggests antiviral therapy when maternal HBV DNA is >200,000 IU/mL.^[5,38,39]

Virus Description and Transmission

HBV is a 40–42-nm enveloped virus classified in the Hepadnaviridae family. HBV contains a circular, partially double-stranded DNA genome that is 3.2 kb in length. After a susceptible person is exposed, the virus enters the liver via the bloodstream. The liver is the primary site of HBV replication.^[40-43]

HBV has been classified by two separate systems: serologic subtype and genotype. Nine serologic subtypes initially were described based on the heterogeneity of HBsAg: adrq+, adrq–, ayr, ayw1, ayw2, ayw3, ayw4, adw2, and adw4.^[44,45] Ten HBV genotypes, designated A–J, have been described. HBV serotypes and genotypes vary geographically. Infection or immunization with one genotype generally confers immunity to all genotypes.^[7,44,46,47]

HBV is highly infectious, can be transmitted in the absence of visible blood,^[22] and remains infectious on environmental surfaces for at least 7 days.^[2,3] All HBsAg-positive persons are infectious, but those with elevated HBV DNA or those with hepatitis B e antigen (HBeAg), a protein from the hepatitis B virus that circulates in the blood and is a marker of infectivity, are most infectious. Persons with occult HBV infection (i.e., those who test negative for HBsAg but have detectable HBV DNA) also might transmit infection.^[48]

HBV is transmitted through percutaneous, mucosal, or nonintact skin exposure to infectious blood or body fluids. HBV is concentrated most highly in blood, and percutaneous exposure is an efficient mode of transmission. Semen and vaginal secretions are infectious, and HBV also can be detected in saliva, tears, and bile. Cerebrospinal fluid, synovial fluid, pleural fluid, peritoneal fluid, pericardial fluid, and amniotic fluid are also considered potentially infectious. Urine, feces, vomitus, nasopharyngeal washings, sputum, and sweat are not efficient vehicles of transmission unless they contain blood because they contain low quantities of infectious HBV. HBsAg found in breast milk is also unlikely to lead to transmission, and hence HBV infection is not a contraindication to breastfeeding.^[2,7,22]

Among adults, HBV is transmitted primarily by percutaneous exposure to blood (e.g., by injection-drug use) and sexual contact. HBV is transmitted efficiently by sexual contact both among heterosexuals and among men who have sex with men (MSM). Risk factors for sexual transmission among heterosexuals include having unprotected sex with an infected partner, having unprotected sex with more than one partner, and a history of another sexually transmitted infection (STI). Risk factors associated with sexual transmission among MSM include having multiple sex partners, history of another STI, and anal intercourse. Transmission can occur from interpersonal contact (e.g., sharing a toothbrush or razor, contact with exudates from dermatologic lesions, or contact with HBsAg-contaminated surfaces) and in settings such as schools, child care centers, and facilities for developmentally disabled persons. Transmission of HBV from transfusion of blood or blood products is rare because of donor screening and viral inactivation procedures. Other possible sources of infection include contaminated medical or dental instruments, unsafe injections, needle-stick injuries, organ transplantation, and dialysis.^[49]

Clinical Features and Natural History

Clinical manifestations of HBV infection range from asymptomatic infection to fulminant hepatitis. The average incubation period is 60 days (range: 40–90 days) from exposure to onset of abnormal serum ALT levels and 90 days (range: 60–150 days) from exposure to onset of jaundice.^[8,42,43] Infants, children aged <5 years, and immunosuppressed adults with newly acquired HBV infection typically are asymptomatic, whereas symptomatic illness is noted in 30%–50% of older children, adolescents, and adults.^[7,8,44,50] When present, signs and symptoms include nausea, vomiting, abdominal pain, fever, dark urine, changes in stool color, hepatomegaly, splenomegaly, and jaundice. Malaise and anorexia might precede jaundice by 1–2 weeks. Fulminant HBV infection is uncommon (<1%) but often results in death or liver failure necessitating liver transplantation. Extrahepatic manifestations of disease (e.g., skin rash, arthralgias, and arthritis) also might occur.^[51] The fatality rate among persons with reported cases of acute HBV infection is <1.5%, with the highest rates in adults aged ≥55 years. Because a substantial number of infections are asymptomatic and therefore are not reported, the overall fatality rate among all persons with HBV infection is likely lower.^[8]

Chronic infection occurs among 80%–90% of persons infected during infancy, 30% of persons infected before age 6 years, and <1%–12% of persons infected as an older child or adult.^[7,52-54] Approximately 95% of primary infections in immunocompetent adults are self-limited, with elimination of the virus from blood and generally immunity to reinfection. Chronic infection develops more frequently in immunosuppressed persons (e.g., hemodialysis patients and persons with human immunodeficiency virus [HIV] infection)^[54,55] and persons with diabetes.^[54] Chronic HBV infection can result in cirrhosis of the liver, liver cancer, liver failure, and death. Approximately 25% of persons who become chronically infected during childhood and 15% of those who become chronically infected after childhood will die prematurely from cirrhosis or liver cancer.^[8,56-58]

There are four phases of chronic HBV infection: immune tolerant, immune active, immune inactive, and reactivation. Chronically infected persons do not necessarily pass through these phases in a linear fashion. Persons in the immune tolerant phase have no or minimal hepatic inflammation or fibrosis; most chronically infected children will remain in the immune tolerant phase until late childhood or adolescence. The immune active phase is characterized by an active immune response resulting in hepatic inflammation, with or without fibrosis. Persons who remain in the immune active phase for prolonged periods of time are at high risk for developing cirrhosis and hepatocellular carcinoma. Persons in the immune inactive phase have improvement of hepatic inflammation and fibrosis. Risk for progression to hepatocellular carcinoma is lower among persons in the immune inactive phase compared with the active phase. Persons in the reactivation phase have active liver inflammation with or without fibrosis.^[44,59-61] HBV reactivation might occur with immunosuppressive therapy or treatment for HCV.^[62]

No specific treatment exists for acute HBV infection; supportive care is the mainstay of therapy. Guidelines for management of chronic HBV infection in children and adults, including disease monitoring and antiviral therapy, are available.^[5] Antiviral therapy generally should be initiated in patients with chronic HBV infection who are likely to respond to treatment and who are at high risk for liver-related morbidity.^[5] Maternal antiviral therapy to reduce perinatal transmission is suggested for HBsAg-positive pregnant women whose HBV DNA level is >200,000 IU/mL.^[5]

In areas in which HBV is highly endemic, HBV frequently is transmitted perinatally from HBV-infected pregnant women to their newborns. The majority of cases of perinatal HBV transmission occur during delivery, with rare instances of in utero transmission.^[63] HBV transmission might occur in germ cell lines, as the virus has been detected in sperm, oocytes, and embryos. Available data do not support the need for a cesarean delivery among HBV-infected pregnant women with low HBV DNA.^[63] Prior to the widespread availability of postexposure prophylaxis, the proportion of infants born to HBsAg-positive women acquiring HBV infection was approximately 30% for those born to HBeAg-negative mothers and 85% for those born to HBeAg-positive mothers. With postexposure prophylaxis, comprised of HepB vaccine and HBIG at birth, followed by completion of the HepB vaccine series, 0.7%–1.1% of infants develop infection^[28,29,64]; infants born to mothers with high viral loads are at greatest risk for infection despite receipt of HepB vaccine and HBIG.^[29] Unvaccinated infants and children are also at risk for horizontal transmission from infected household and other contacts.

Interpretation of Serologic Markers

Serologic markers for HBV infection include HBsAg, antibody to HBsAg (anti-HBs), immunoglobulin class M (IgM) antibodies to hepatitis B core antigen (IgM anti-HBc), and immunoglobulin class G (IgG) anti-HBc (IgG anti-HBc).^[49,65,66] At least one serologic marker is present during the different phases of infection. HBV DNA is a measure of viral load and reflects viral replication^[49] ( Table 1 ). Hepatitis B e antigen (HBeAg) can be detected in persons with acute or chronic HBV infection; the presence of HBeAg correlates with viral replication and high infectivity; antibody to HBeAg (anti-HBe) correlates with the loss of replicating virus, although reversion to HBeAg positivity can occur.^[7]

A confirmed positive HBsAg result indicates current HBV infection, either acute or chronic. All HBsAg-positive persons are infectious. If HBsAg persists for >6 months, spontaneous clearance is unlikely, and the infection is deemed chronic. HBV DNA can be detected prior to the detection of HBsAg in an infected person. Occult infection occurs when HBsAg is undetectable despite the presence of HBV DNA.^[66-68] Transient HBsAg positivity can occur up to 18 days following vaccination (up to 52 days among hemodialysis patients) and is clinically insignificant.^[69]

In acute HBV infection, anti-HBc (initially both IgM and IgG) appears 1–2 weeks after the appearance of HBsAg^[49] (Figure 2). IgM anti-HBc often becomes undetectable within 6 months, and IgG anti-HBc predominates and remains detectable for a lengthy period of time, often life-long.^[65,66] The presence of IgM anti-HBc is indicative of acute infection, while IgG anti-HBc indicates past infection.^[65,66] In persons who recover from HBV infection, HBsAg is eliminated from the blood and anti-HBs develops, typically within 3–4 months. The presence of anti-HBs is generally indicative of immunity to HBV infection.^[8] Anti-HBs also can be detected for 4–6 months following HBIG administration.^[10] Persons who recover from natural HBV infection are typically positive for both anti-HBs and anti-HBc, whereas persons who respond to HepB vaccine are positive only for anti-HBs. Approximately 0.5%–2% of persons with chronic infection spontaneously clear HBsAg yearly; anti-HBs will develop in the majority of these persons.^[8]

Enlarge

Figure 2. Acute hepatitis B virus infection with recovery
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; HBsAg = hepatitis B surface antigen; HBV DNA = hepatitis B virus deoxyribonucleic acid; IgM = immunoglobulin class M.

In certain persons, anti-HBc is the only serologic marker detected. Isolated anti-HBc-positivity can be detected following HBV infection in persons who have recovered but whose anti-HBs levels have waned; in populations with a high prevalence of HBV infection, isolated anti-HBc likely indicates previous infection with loss of anti-HBs. Some chronically infected persons with isolated anti-HBc-positivity have circulating HBsAg that is not detectable by a laboratory assay. HBV DNA has been detected in <10% of persons with isolated anti-HBc,^[70,71] although the presence of detectable HBV DNA might fluctuate.^[72] These persons are unlikely to transmit infection except under circumstances in which they are the source of a large exposure, such as a blood transfusion.^[8,73] Persons who are HBsAg-negative and anti-HBc-positive can experience reactivation of infection during chemotherapy or immunosuppressive therapy, with reappearance of HBsAg.^[49] Infection with a mutant HBV strain can result in positive laboratory tests for HBsAg, total anti-HBc, anti-HBs, and HBV DNA, with a negative IgM anti-HBc.

Perinatal HBV infection in a child aged ≤24 months is typically asymptomatic although fulminant hepatitis can occur; a positive HBsAg test, positive HBeAg test, or detectable HBV DNA may be considered laboratory evidence of perinatal HBV in an infant born to an HBV-infected mother if timing criteria are met.^[74] Infants who are born to HBsAg-positive mothers and who do not become infected might have detectable anti-HBc for up to 24 months after birth from passively acquired maternal antibody.^[7]

Adults at Risk for HBV Infection

In 2015, CDC received 3,370 surveillance case-reports of acute HBV infection. Of 2,207 case-reports with risk information, 1,151 (52.2%) indicated no risk for HBV during the 6 weeks to 6 months prior to illness onset, and the remainder indicated at least one risk factor. Injection-drug use and multiple sex partners were the most common reported sources of HBV transmission.^[4]

Injection-drug use. Injection-drug use was reported by 30.3% of 1,657 new reported HBV cases that included information about injection-drug use.^[4] Since 2009, there has been an increase in acute HBV infection among non-Hispanic whites aged 30–39 years residing in nonurban areas reporting injection-drug use as a risk factor.^[16] Chronic HBV infection has been identified in 3.5%-20.0% (midpoint estimate: 11.8%) of persons who inject drugs (PWID) in a variety of settings^[75] and 22.6% of PWID have evidence of past infection.^[75] The proportion of HBV cases reporting injection-drug use in three states (Kentucky, Tennessee, and West Virginia) increased significantly, from 53% during 2006–2009 to 75% during 2010–2013 (p<0.001, chi-square).^[16]

Sexual (heterosexual and MSM) exposure. Among persons with case-reports of HBV infection with information about sexual exposure, 26.4% reported having two or more sexual partners, 3.3% reported sexual contact with an HBV-infected person, and 11.8% of males reported having had sex with another male.^[4] As many as 10%–40% of adults seeking treatment in STI clinics have evidence of current or past HBV infection. Among adults with acute HBV infection, 39% were screened or sought care for an STI prior to becoming infected with HBV.^[76]

Household contacts. An estimated 45% of persons living in households with others with chronic HBV infection have serologic evidence of past HBV infection, and 16% have evidence of current infection (CDC, unpublished data, 2017. Prior to universal infant vaccination, the risk for infection was greatest among unvaccinated children living with a person with chronic HBV infection in a household or in an extended family setting.^[67,77,78]

Developmentally disabled persons in long-term-care facilities. Developmentally disabled persons in residential and nonresidential facilities historically have had a chronic HBV infection prevalence as high as 20%. The prevalence of infection has declined substantially since the implementation of routine HepB vaccination in these settings.^[79-82]

Correctional facilities. The prevalence of chronic HBV infection has been higher among prison inmates (1.0%–3.7%) than among the general population,^[83,84] reflecting an overrepresentation of persons entering correctional facilities with risks for HBV infection (e.g., injection-drug use and histories of multiple sex partners).

Persons at risk for occupational exposure to HBV. Before HepB vaccination was widely implemented, HBV infection was recognized as a common occupational risk among HCP.^[85,86] Routine HepB vaccination of HCP and the use of standard precautions have resulted in a 98% decline in HBV infections from 1983 through 2010 among HCP.^[10] The Occupational Safety and Health Administration mandates that employers offer HepB vaccination to all employees who have occupational risk and that postexposure prophylaxis be available following an exposure.^[10,87]

Hemodialysis patients. Since the initiation of HepB vaccination and additional infection control precautions for hepatitis B in dialysis centers, the incidence of HBV infection among hemodialysis patients has declined approximately 95%.^[88,89] Since 1995, the annual incidence has been stable and HBsAg seroprevalence has remained at 1%.^[90] Receipt of dialysis was reported in <1% of acute HBV surveillance cases with information reported to CDC.^[4]

Persons with HCV infection. The number of reported HCV cases in four Appalachian states (Kentucky, Tennessee, Virginia, and West Virginia) increased 364% during 2006–2012 among persons aged =30 years, with injection-drug use as the most common reported risk factor.^[91] The increase in HCV infections occurred concomitantly with an increase in HBV infections among young adults in rural communities in Appalachian states.

Persons with chronic liver disease. Persons with chronic liver disease (e.g., cirrhosis, fatty liver disease, alcoholic liver disease, and autoimmune hepatitis) are not at increased risk for HBV infection unless they have percutaneous or mucosal exposure to blood or body fluids. However, concurrent chronic HBV infection might increase the risk for progressive chronic liver disease in these persons.^[92]

Travelers to countries where HBV is endemic. Short-term travelers to countries in which HBV infection is of high or intermediate endemicity ( Box 3 ) typically are at risk for infection only through exposure to blood in medical or disaster-relief activities, receipt of medical care that involves parenteral exposures, sexual activity, or drug use. Monthly incidence of 25–420 per 100,000 travelers has been reported among long-term travelers to countries where the disease is endemic.^[93]

Persons with HIV. Approximately 10% of HIV-positive persons are coinfected with HBV.^[94-97] Chronic HBV infection has been identified in 6%–14% of HIV-positive persons, including in 9%–17% of MSM and in 7%–10% of PWID.^[98] Coinfected persons have increased rates of cirrhosis and liver-related mortality.^[99]

Persons with diabetes. Compared with adults without diabetes, adults with diabetes have a 60% higher prevalence of past or present HBV infection and twice the odds of acquiring acute HBV. Repeated outbreaks of HBV infection associated with assisted blood glucose monitoring underscore the continued risk for this population.^[100-102] Data also suggest the possibility of a higher case-fatality proportion among persons with diabetes acutely infected with HBV compared with those without diabetes.^[9]

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Page 5 of 12

Prophylaxis Against HBV Infection

CME / ABIM MOC / CE Information

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: HBV Background

HBV Background

Epidemiology

Strategy to Eliminate HBV

Virus Description and Transmission

Clinical Features and Natural History

Interpretation of Serologic Markers

Adults at Risk for HBV Infection

Table of Contents