Postexposure prophylaxis (PEP) with hepatitis A (HepA) vaccine or immune globulin
(IG) effectively prevents infection with hepatitis A virus (HAV) when administered
within 2 weeks of exposure. Preexposure prophylaxis against HAV infection through
the administration of HepA vaccine or IG provides protection for unvaccinated persons
traveling to or working in countries that have high or intermediate HAV endemicity.
The Advisory Committee on Immunization Practices (ACIP) Hepatitis Vaccines Work Group
conducted a systematic review of the evidence for administering vaccine for PEP to
persons aged >40 years and reviewed the HepA vaccine efficacy and safety in infants
and the benefits of protection against HAV before international travel. The February
21, 2018, ACIP recommendations update and supersede previous ACIP recommendations
for HepA vaccine for PEP and for international travel. Current recommendations include
that HepA vaccine should be administered to all persons aged ≥12 months for PEP. In
addition to HepA vaccine, IG may be administered to persons aged >40 years depending
on the provider’s risk assessment. ACIP also recommended that HepA vaccine be administered
to infants aged 6–11 months traveling outside the United States when protection against
HAV is recommended. The travel-related dose for infants aged 6–11 months should not
be counted toward the routine 2-dose series. The dosage of IG has been updated where
applicable (0.1 mL/kg). HepA vaccine for PEP provides advantages over IG, including
induction of active immunity, longer duration of protection, ease of administration,
and greater acceptability and availability.
Introduction
Postexposure prophylaxis (PEP) with hepatitis A (HepA) vaccine or immune globulin
(IG) effectively prevents infection with hepatitis A virus (HAV) when administered
within 2 weeks of exposure (
1
,
2
). The efficacy of IG or vaccine when administered >2 weeks after exposure has not
been established. Previous ACIP* recommendations for PEP included HepA vaccine for
persons aged 1–40 years and IG for persons outside this age range; if IG was not available
for persons aged >40 years, HepA vaccine could be administered (
1
).
Preexposure prophylaxis against HAV infection through the administration of HepA vaccine
or IG is also recommended for unvaccinated persons traveling to or working in countries
that have high or intermediate HAV endemicity (
3
). Because HepA vaccine is not licensed for use in children aged <1 year, IG has historically
been recommended for travelers in this age group; however, IG cannot be administered
simultaneously with measles, mumps, and rubella (MMR) vaccine, which is also recommended
for infants aged 6–11 months traveling internationally from the United States (
4
–
6
).
This report provides recommendations for PEP use of HepA vaccine and IG, and use of
HepA vaccine and IG for preexposure protection for persons who will be traveling internationally,
including infants aged 6–11 months. This report updates and supersedes previous ACIP
recommendations for HepA vaccine for PEP and for international travel (
1
).
Methods
During November 2016–February 2018, the ACIP Hepatitis Work Group
†
held monthly conference calls to review and discuss relevant scientific evidence,
§
including the use of HepA vaccine and IG for PEP and the use of HepA vaccine for infants
before some international travel. The ACIP Hepatitis Work Group evaluated the quality
of evidence related to the benefits and harms of administering a dose of HepA vaccine
for PEP for persons aged >40 years using the Grading of Recommendations Assessment,
Development, and Evaluation (GRADE) framework (https://www.cdc.gov/vaccines/acip/recs/grade/table-refs.html).
Quality of evidence related to the benefits and harms of administering HepA vaccine
for preexposure prophylaxis to infants aged 6–11 months who will be traveling internationally
was not evaluated using the GRADE framework; instead, studies of HepA vaccine efficacy
and safety in infants (
7
–
9
) and the benefits of protection against HAV before international travel were considered
(
3
).
At the February 2018 ACIP meeting, the following proposed recommendations were presented
to the committee: 1) HepA vaccines should be administered for PEP for all persons
aged ≥12 months; in addition to HepA vaccine, IG may be administered to persons aged
>40 years for PEP, depending on the provider’s risk assessment; and 2) HepA vaccine
should be administered to infants aged 6–11 months traveling outside the United States
when protection against hepatitis A is recommended. After a period for public comment,
the recommendations were approved unanimously by the voting ACIP members.
¶
Summary of Key Findings
Prevention of HAV infection with HepA vaccine following exposure. A randomized, double-blind
clinical trial of HepA vaccine in 1,090 HAV-susceptible persons aged 2–40 years who
were contacts of persons with HAV infection suggested that performance of HepA vaccine
administered <14 days after exposure approaches that of IG in healthy children and
adults aged <40 years (
1
,
10
). Limited data are available comparing HepA vaccine and IG in healthy adults aged
>40 years; available data indicate reduced response to HepA vaccine in older age groups
compared with response in younger adults (
11
).
GRADE quality of evidence summary for HepA vaccine for PEP in persons aged >40 years.
The evidence assessing benefits and harms of administering a dose of HepA vaccine
for PEP to prevent HAV infection in adults aged >40 years was determined to be GRADE
evidence type 4 (i.e., evidence from clinical experience and observations, observational
studies with important limitations, or randomized controlled trials with several major
limitations) for benefits and type 3 (i.e., evidence from observational studies, or
randomized controlled trials with notable limitations) for harms (https://www.cdc.gov/vaccines/acip/recs/grade/table-refs.html).
Prevention of HAV infection among infants aged 6–11 months who received HepA vaccine
before travel. HepA vaccine was demonstrated to be safe and efficacious for infants
as young as age 2 months (
2
,
7
–
9
), although vaccination of infants aged <12 months might result in a suboptimal immune
response because of potential interference with passively acquired maternal antibody,
which could decrease long-term immunity (
7
–
9
).
Rationale for Recommendations
Advantages of HepA vaccine for PEP. HepA vaccine for PEP provides numerous public
health advantages compared with IG, including the induction of active immunity and
longer duration of protection, ease of administration, and greater acceptability and
availability (
11
). Previous recommendations favoring IG for adults aged >40 years were based on the
premise that IG is more efficacious in this group; however, evidence of decreased
IG potency (i.e., reduced titers of anti-HAV antibodies) (
12
) led to a recommendation for an increase in the IG dosage (0.1 mL/kg) for hepatitis
A PEP in 2017, with a consequent increase in IG administration volume (
6
). In addition, when HAV exposure, and thus the need for PEP, is not clear (i.e.,
consumer of recalled food product or patron at a restaurant where a notification occurred),
the benefit of IG compared with vaccine, which provides long-term protection, is less
certain.
Before travel administration of HepA vaccine to infants aged 6–11 months. IG cannot
be administered simultaneously with MMR vaccine because antibody-containing products
such as IG can inhibit the immune response to measles and rubella vaccines for 3 months
(
4
,
6
). However, because MMR vaccine is recommended for all infants aged 6–11 months traveling
internationally from the United States and because measles in infancy is more severe
than HAV infection in infancy, MMR vaccine should be administered preferentially to
preexposure prophylaxis with IG for prevention of HAV infection. Administration of
HepA vaccine (indication for off-label use) and MMR vaccine to infants aged 6–11 months
(
7
–
9
) provides protection against both HAV and measles and allows for simultaneous prophylactic
administration (
4
,
13
).
Recommendations for Postexposure Prophylaxis Against HAV Infection
HepA vaccine should be administered to all persons aged ≥12 months for PEP. In addition
to HepA vaccine, IG may be administered to persons aged >40 years, depending on the
provider’s risk assessment (Supplementary Text 1, https://staging-stacks.cdc.gov/view/cdc/59777).
Recommendations for PEP have been updated to include HepA vaccine for all unvaccinated
persons aged ≥12 months, regardless of risk group, and co-administration of IG when
indicated (Table 1). The dosage of GamaSTAN S/D human IG for PEP (0.1 mL/kg) also
has been updated (
6
). Persons who have recently been exposed to HAV and who have not received HepA vaccine
previously should receive PEP as soon as possible, within 2 weeks of exposure (
1
).
TABLE 1
Recommendations for postexposure prophylaxis and preexposure protection, by age group
and risk category
Indication/Age group
Risk category/Health status
Hepatitis A vaccine
Immune globulin
Postexposure prophylaxis
<12 mos
Healthy
No
0.1 mL/kg*
12 mos–40 yrs
Healthy
1 dose†
None
>40 yrs
Healthy
1 dose†
0.1 mL/kg§
≥12 mos
Immunocompromised or chronic liver disease
1 dose†
0.1 mL/kg¶
≥12 mos
Vaccine contraindicated**
No
0.1 mL/kg
Preexposure protection††
<6 mos
Healthy
No
0.1–0.2 mL/kg§§
6–11 mos
Healthy
1 dose¶¶
None
12 mos–40 yrs
Healthy
1 dose***
None
>40 yrs
Healthy
1 dose***
0.1–0.2 mL/kg§§,†††
All ages
Immunocompromised or chronic liver disease
1 dose***
0.1–0.2 mL/kg§§,†††
>6 mos
Persons who elect not to receive vaccine or for whom vaccine is contraindicated**
No
0.1–0.2 mL/kg§§
* Measles, mumps, and rubella vaccine should not be administered for at least 3 months
after receipt of IG.
† A second dose is not required for postexposure prophylaxis; however, for long-term
immunity, the hepatitis A vaccination series should be completed with a second dose
at least 6 months after the first dose.
§ The provider’s risk assessment should determine the need for immune globulin administration.
If the provider’s risk assessment determines that both vaccine and immune globulin
are warranted, HepA vaccine and immune globulin should be administered simultaneously
at different anatomic sites
¶ Vaccine and immune globulin should be administered simultaneously at different anatomic
sites.
** Life-threatening allergic reaction to a previous dose of hepatitis A vaccine, or
allergy to any vaccine component.
†† IG should be considered before travel for persons with special risk factors for
either HAV infection or increased risk for complications in the event of exposure
to HAV.
§§ 0.1 mL/kg for travel up to 1 month; 0.2 mL/kg for travel up to 2 months, 0.2mL/kg
every 2 months for travel of ≥2 months’ duration.
¶¶ This dose should not be counted toward the routine 2-dose series, which should
be initiated at age 12 months.
*** For persons not previously vaccinated with HepA vaccine, administer dose as soon
as travel is considered, and complete series according to routine schedule.
††† May be administered, based on providers’ risk assessment.
Infants aged <12 months and persons for whom vaccine is contraindicated. Infants aged
<12 months and persons for whom vaccine is contraindicated (persons who have had a
life-threatening allergic reaction after a dose of HepA vaccine, or who have a severe
allergy to any component of this vaccine) should receive IG (0.1 mL/kg) (
6
,
14
) instead of HepA vaccine, as soon as possible and within 2 weeks of exposure. MMR
and varicella vaccines should not be administered sooner than 3 months after IG administration
(
4
–
6
).
Immunocompetent persons aged ≥12 months. Persons aged ≥12 months who have been exposed
to HAV within the past 14 days and have not previously completed the 2-dose HepA vaccine
series should receive a single dose of HepA vaccine (Table 2) as soon as possible.
In addition to HepA vaccine, IG (0.1 mL/kg) may be administered to persons aged >40
years depending on the providers’ risk assessment (Supplementary Text 1, https://staging-stacks.cdc.gov/view/cdc/59777).
For long-term immunity, the HepA vaccine series should be completed with a second
dose at least 6 months after the first dose; however, the second dose is not necessary
for PEP. A second dose should not be administered any sooner than 6 months after the
first dose, regardless of HAV exposure risk.
TABLE 2
Vaccines used to prevent hepatitis A virus (HAV) infection
Vaccine
Trade name (manufacturer)
Age group (yrs)
Dosage
Route
Schedule
Booster
Hepatitis A vaccine, inactivated
Havrix (GlaxoSmithKline)
1–18
0.5 mL (720 ELU)
IM
0, 6–12 mo
None
≥19
1 mL (1,440 ELU)
IM
0, 6–12 mo
None
Hepatitis A vaccine, inactivated
Vaqta (Merck and Co.)
1–18
0.5 mL (25 U)
IM
0, 6–18 mo
None
≥19
1 mL (50 U)
IM
0, 6–18 mo
None
Combined hepatitis A and B vaccine*
Twinrix (GlaxoSmithKline)
≥18 (primary)
1 mL (720 ELU HAV + 20 μg HBsAg)
IM
0, 1, 6 mo
None
≥18 (accelerated)
1 mL (720 ELU HAV + 20 μg HBsAg)
IM
0, 7, 21–30 days
12 mo
Abbreviations: ELU = ELISA units of inactivated HAV; HBsAg = hepatitis B surface antigen;
IM = intramuscular; U = units of HAV antigen.
* Combined hepatitis A and B vaccine (Twinrix) should not be used for postexposure
prophylaxis.
Persons aged ≥12 months who are immunocompromised or have chronic liver disease. Persons
who are immunocompromised or have chronic liver disease and who have been exposed
to HAV within the past 14 days and have not previously completed the 2-dose HepA vaccination
series should receive both IG (0.1 mL/kg) and HepA vaccine simultaneously in a different
anatomic site (e.g., separate limbs) as soon as possible after exposure (
6
,
15
–
17
) (Table 1). For long-term immunity, the HepA vaccination series should be completed
with a second dose at least 6 months after the first dose; however, the second dose
is not necessary for PEP. A second dose should not be administered any sooner than
6 months after the first dose, regardless of HAV exposure risk.
In addition to HepA vaccine, IG should be considered for postexposure prophylaxis
for persons with special risk factors for either HAV infection or increased risk of
complications in the event of an exposure to HAV (Table 3) (Supplementary Text 1,
https://staging-stacks.cdc.gov/view/cdc/59777).
TABLE 3
Categories of persons with increased risk for hepatitis A virus (HAV) infection or
increased risk for complications in the event of exposure to HAV
Type of risk
Risk category
Examples
Increased risk for HAV infection
Close contacts of persons with HAV infection*
Household contacts
Caretakers
Sexual contacts
Occupational risk
Persons working with nonhuman primates
Persons working with HAV in a research laboratory
Increased risk for HAV-associated complications
Immunocompromised persons
Congenital or acquired immunodeficiency
HIV infection
Chronic renal failure/Undergoing dialysis
Solid organ, bone marrow, or stem cell transplant recipients
Persons with diseases requiring treatment with immunosuppressive drugs/biologics (e.g.,
tumor necrosis alpha inhibitors), long-term systemic corticosteroids, radiation therapy
Chronic liver disease
Hepatitis B infection
Hepatitis C infection
Cirrhosis (any etiology)
Fatty liver disease (hepatic steatosis)
Alcoholic liver disease
Autoimmune hepatitis
Alanine aminotransferase (ALT) or aspartate amino transferase (AST) level more than
twice the upper limit of normal or persistently elevated for 6 months
Abbreviation: HIV = human immunodeficiency virus.
* Excludes health care personnel using appropriate personal protective equipment.
Recommendations for Preexposure Protection Against HAV Infection for Travelers
Infants aged 6–11 months. HepA vaccine should be administered to infants aged 6–11
months traveling outside the United States when protection against HAV is recommended
(Table 1). The travel-related dose for infants aged 6–11 months should not be counted
toward the routine 2-dose series. Therefore, the 2-dose HepA vaccination series should
be initiated at age 12 months according to the routine, age-appropriate vaccination
schedule.
Recommendations for preexposure protection against HAV for travelers aged <6 months
and aged ≥12 months remain unchanged from previous recommendations (Table 1), except
for the updated dosage of IG where applicable (Supplementary Text 2, https://staging-stacks.cdc.gov/view/cdc/59778)
(
6
). For travel duration up to 1 month, 0.1 mL/kg of IG is recommended; for travel up
to 2 months, the dose is 0.2 mL/kg, and for travel of ≥2 months, a 0.2 mL/kg dose
should be repeated every 2 months for the duration of travel. All susceptible persons
traveling to or working in countries that have high or intermediate HAV endemicity
are at increased risk for infection and should be vaccinated or receive IG before
departure (
1
,
3
).
Infants aged <6 months and travelers who elect not to receive vaccine or for whom
vaccine is contraindicated. Infants aged <6 months and travelers who elect not to
receive vaccine or for whom vaccine is contraindicated should receive a single dose
of IG before travel when protection against HAV is recommended. If travel is for ≥2
months’ duration, a repeat dose of 0.2 mL/kg every 2 months should be administered
(
6
).
Healthy persons aged 12 months–40 years. Healthy persons aged 12 months–40 years who
are planning travel to an area with high or intermediate HAV endemicity and have not
received HepA vaccine should receive a single dose of HepA vaccine as soon as travel
is considered and should complete the 2-does series according to the routine schedule.
Persons aged >40 years, immunocompromised persons, and persons with chronic liver
disease. Persons with chronic liver disease as well as adults aged >40 years, immunocompromised
persons, and persons with other chronic medical conditions planning to depart to an
area with high or intermediate HAV endemicity in <2 weeks should receive the initial
dose of HepA vaccine, and also simultaneously may be administered IG at a separate
anatomic injection site (e.g., separate limbs) (Table 1) (
6
,
15
–
17
).
In addition to HepA vaccine, IG should be considered before travel for persons with
special risk factors for either HAV infection or increased risk for complications
in the event of an exposure to HAV (Table 3) (Supplementary Text 2, https://staging-stacks.cdc.gov/view/cdc/59778).
Summary
What is already known about this topic?
Postexposure prophylaxis (PEP) with hepatitis A (HepA) vaccine or immune globulin
(IG) prevents infection with hepatitis A virus when administered within 2 weeks of
exposure. Measles, mumps, and rubella vaccine (MMR) is recommended for infants aged
6–11 months traveling outside the United States. IG cannot be administered simultaneously
with MMR.
What is added by this report?
HepA vaccine is recommended for persons aged ≥12 months for PEP. Providers may also
administer IG to adults aged >40 years, if indicated. The dosage of IG has been updated.
Simultaneous administration of MMR and HepA vaccines is recommended for infants aged
6–11 months traveling internationally.
What are the implications for public health practice?
HepA vaccine for PEP provides advantages over IG, including induction of active immunity,
longer duration of protection, ease of administration, and greater acceptability and
availability.