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Morbidity and Mortality Weekly Report


Recommendations and Reports / Vol. 72 / No. 1 March 10, 2023

Screening and Testing for Hepatitis B Virus Infection:


CDC Recommendations — United States, 2023

U.S. Department of Health and Human Services


Centers for Disease Control and Prevention
Recommendations and Reports

CONTENTS
Introduction.............................................................................................................1
Methods.....................................................................................................................5
Universal Screening Systematic Review and Review of
Evidence Summary.............................................................................................6
Cost-Effectiveness of Screening Strategies...................................................8
Universal Screening Summary of Findings...................................................9
Rationale for New Recommendations......................................................... 13
HBV Screening and Testing Recommendations....................................... 14
Recommendations and Guidance from Non-CDC Sources................. 19
Future Directions................................................................................................. 20
Conclusion............................................................................................................. 20
References.............................................................................................................. 20

The MMWR series of publications is published by the Office of Science, Centers for Disease Control and Prevention (CDC), U.S. Department of Health and
Human Services, Atlanta, GA 30329-4027.
Suggested citation: [Author names; first three, then et al., if more than six.] [Title]. MMWR Suppl 2023;72(Suppl-#):[inclusive page numbers].

Centers for Disease Control and Prevention


Rochelle P. Walensky, MD, MPH, Director
Debra Houry, MD, MPH, Chief Medical Officer and Deputy Director for Program and Science
Rebecca Bunnell, PhD, MEd, Director, Office of Science

MMWR Editorial and Production Staff (Serials)


Charlotte K. Kent, PhD, MPH, Editor in Chief Martha F. Boyd, Lead Visual Information Specialist Ian Branam, MA,
Rachel Gorwitz, MD, MPH, Acting Executive Editor Alexander J. Gottardy, Maureen A. Leahy, Lead Health Communication Specialist
Christine G. Casey, MD, Editor Julia C. Martinroe, Stephen R. Spriggs, Tong Yang, Kiana Cohen, MPH, Symone Hairston, MPH,
Mary Dott, MD, MPH, Online Editor Visual Information Specialists Leslie Hamlin, Lowery Johnson,
Terisa F. Rutledge, Managing Editor Quang M. Doan, MBA, Phyllis H. King, Health Communication Specialists
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Marella Meadows, Project Editor Information Technology Specialists Visual Information Specialists

MMWR Editorial Board


Timothy F. Jones, MD, Chairman
Matthew L. Boulton, MD, MPH David W. Fleming, MD Patrick L. Remington, MD, MPH
Carolyn Brooks, ScD, MA William E. Halperin, MD, DrPH, MPH Carlos Roig, MS, MA
Virginia A. Caine, MD Jewel Mullen, MD, MPH, MPA William Schaffner, MD
Jonathan E. Fielding, MD, MPH, MBA Jeff Niederdeppe, PhD Morgan Bobb Swanson, BS
Patricia Quinlisk, MD, MPH
Recommendations and Reports

Screening and Testing for Hepatitis B Virus Infection:


CDC Recommendations — United States, 2023
Erin E. Conners, PhD1; Lakshmi Panagiotakopoulos, MD1; Megan G. Hofmeister, MD1; Philip R. Spradling, MD1; Liesl M. Hagan, MPH1;
Aaron M. Harris, MD1; Jessica S. Rogers-Brown, PhD1; Carolyn Wester, MD1; Noele P. Nelson, MD, PhD1

1Division of Viral Hepatitis, National Center for HIV, Viral Hepatitis, STD, and TB Prevention, CDC

Summary
Chronic hepatitis B virus (HBV) infection can lead to substantial morbidity and mortality. Although treatment is not considered
curative, antiviral treatment, monitoring, and liver cancer surveillance can reduce morbidity and mortality. Effective vaccines
to prevent hepatitis B are available. This report updates and expands CDC’s previously published Recommendations for
Identification and Public Health Management of Persons with Chronic Hepatitis B Virus Infection (MMWR Recomm
Rep 2008;57[No. RR-8]) regarding screening for HBV infection in the United States. New recommendations include hepatitis B
screening using three laboratory tests at least once during a lifetime for adults aged ≥18 years. The report also expands risk-based
testing recommendations to include the following populations, activities, exposures, or conditions associated with increased risk for
HBV infection: persons incarcerated or formerly incarcerated in a jail, prison, or other detention setting; persons with a history
of sexually transmitted infections or multiple sex partners; and persons with a history of hepatitis C virus infection. In addition,
to provide increased access to testing, anyone who requests HBV testing should receive it, regardless of disclosure of risk, because
many persons might be reluctant to disclose stigmatizing risks.

Introduction an increase in the proportion of persons with HBV infection


who are aware of their infection from 32% (2013–2016) to
Persons with chronic hepatitis B virus (HBV) infection are at 90% by 2030 (12,13). In support of this goal, this report
increased risk for liver cancer and cirrhosis and are 70%–85% updates the 2008 CDC recommendations for risk-based testing
more likely to die prematurely than the general population and management of persons with chronic HBV infection in the
(1–4). An estimated 580,000 to 2.4 million persons are living United States (14). This report is a resource to advise health
with HBV infection in the United States (5,6), two thirds care professionals, public health officials, and organizations
of whom might be unaware of their infection (5). Chronic supporting awareness, prevention, and linkage to care about
HBV infection disproportionately affects persons born outside who to screen for HBV infection and which groups at risk for
the United States; non-U.S.–born persons account for 14% infection to test periodically (Box 1).
of the general population, but account for 69% of the U.S.
population living with chronic HBV infection (5–7).
HBV is transmitted through contact with infected blood Interpretation of Screening Tests
or body fluids, such as during pregnancy or delivery, through The three main serologic markers used to determine HBV
sex, or by injection drug use (IDU), with the greatest risk for infection status are hepatitis B surface antigen (HBsAg),
chronic infection occurring during perinatal infection (8). antibody to hepatitis B surface antigen (anti-HBs), and
Hepatitis B (HepB) vaccination is highly effective in preventing antibody to hepatitis B core antigen (anti-HBc) (Table 1).
HBV infection and subsequent liver disease; however, 70% of Serologic markers change over typical courses of resolved acute
adults in the United States self-reported they were unvaccinated infection and progression to chronic infection (Figure 1) (15).
as of 2018 (9). Although treatment is not considered curative, • HBsAg: The presence of HBsAg indicates HBV infection,
antiviral treatment, monitoring, and liver cancer surveillance either acute or chronic, except when it might be transiently
can reduce morbidity and mortality (10,11). positive shortly after a dose of HepB vaccine (16). The
To provide a framework for reaching the World Health American Association for the Study of Liver Diseases
Organization’s viral hepatitis elimination goals, the Viral (AASLD) defines chronic infection as the presence of
Hepatitis National Strategic Plan for the United States calls for HBsAg for at least 6 months (11).
• Anti-HBs: The appearance of anti-HBs after a decline of
Corresponding author: Erin E. Conners, Division of Viral Hepatitis, HBsAg indicates recovery from HBV infection. Among
National Center for HIV, Viral Hepatitis, STD, and TB Prevention, immunocompetent persons never infected with HBV,
CDC. Telephone: 404-718-7086; Email: econners@cdc.gov.
anti-HBs at concentrations of ≥10 mIU/mL at 1–2 months

US Department of Health and Human Services/Centers for Disease Control and Prevention MMWR / March 10, 2023 / Vol. 72 / No. 1 1
Recommendations and Reports

after completion of a HepB vaccine series indicates identifying a person with HBV infection, testing for
immunity. Although certain persons might have anti-HBs HBeAg, anti-HBe, and HBV DNA can provide
of ≥10 mIU/mL after partial vaccination, whether this information on the level of viral replication and infectivity
confers long-term protection is unknown. Among vaccine and help guide clinical management.
responders who completed a vaccine series, anti-HBs can Background information on HBV, including virus
decline over time to levels of <10 mIU/mL; however, the description, transmission, clinical features, natural history,
majority are still immune and will mount an immune and HepB vaccination seroprotection and coverage, is available
response to a vaccine challenge ≥35 years after vaccination (Supplementary Appendix 1, https://stacks.cdc.gov/view/
(17–20). Hepatitis B immune globulin (HBIG) can cdc/124432).
provide anti-HBs for 4–6 months after administration;
therefore, testing for anti-HBs ≤6 months after HBIG Epidemiology and Risk Factors
administration is not an accurate measure of a person’s
immune status (21). Acute HBV Infection
• Total anti-HBc: Total anti-HBc develops in all HBV Of 3,192 acute HBV infection cases reported to CDC in 2019,
infections, resolved or current, and typically persists for an estimated 20,700 new infections (95% CI = 11,800–50,800)
life. Persons whose immunity to HBV is from a vaccine were identified after adjusting for underascertainment and
do not develop anti-HBc. Assays for total anti-HBc detect underreporting. During 2012–2019, the number of reported
both immunoglobulin M (IgM) and immunoglobulin G acute HBV infection cases in the United States remained
(IgG) antibodies to HBcAg; no test for IgG anti-HBc relatively stable (22,23).
alone is commercially available. During the typical course Geographic differences exist, with the highest rate of cases
of chronic infection, total anti-HBc and HBsAg will be (≥2.5 per 100,000 persons) in 2019 reported by Florida,
present, whereas IgM anti-HBc will disappear (Figure 1). Indiana, Kentucky, Maine, Ohio, Tennessee, and West Virginia
IgM anti-HBc should be ordered only when acute HBV (23). From 2011 to 2017, the percentage of acute HBV
infection is a concern. infections among women of childbearing age was stable
• Other markers (HBV DNA, HBeAg, and anti-HBe): nationally but increased in Alabama (from 0% to 0.3%),
HBV DNA is a measure of viral load. HBeAg is a marker Indiana (from 0% to 0.1%), and Kentucky (from 0.1% to
for viral replication and high infectivity; antibody to 0.2%) (24). Geographic differences in new infections might
HBeAg (anti-HBe) can be used to monitor response to be because of the opioid crisis; during 2006–2013, increases in
treatment and chronic HBV infection progression. After

BOX 1. Hepatitis B virus screening and testing recommendations — CDC, 2023

Universal hepatitis B virus (HBV) screening


• HBV screening at least once during a lifetime for adults aged ≥18 years (new recommendation)
• During screening, test for hepatitis B surface antigen (HBsAg), antibody to HBsAg, and total antibody to HBcAg (total
anti-HBc) (new recommendation)
Screening pregnant persons
• HBV screening for all pregnant persons during each pregnancy, preferably in the first trimester, regardless of vaccination
status or history of testing*
• Pregnant persons with a history of appropriately timed triple panel screening and without subsequent risk for exposure
to HBV (i.e., no new HBV exposures since triple panel screening) only need HBsAg screening
Risk-based testing
• Testing for all persons with a history of increased risk for HBV infection, regardless of age, if they might have been
susceptible during the period of increased risk†
• Periodic testing for susceptible persons, regardless of age, with ongoing risk for exposures, while risk for exposures persists†

* Source: Schillie S, Vellozzi C, Reingold A, et al. Prevention of hepatitis B virus infection in the United States: recommendations of the Advisory Committee
on Immunization Practices. MMWR Recomm Rep 2018;67(No. RR-1):1–31.
† Susceptible persons include those who have never been infected with HBV (i.e., total anti-HBc negative) and either did not complete a HepB vaccine series per
Advisory Committee on Immunization Practices recommendations or who are known to be vaccine nonresponders.

2 MMWR / March 10, 2023 / Vol. 72 / No. 1 US Department of Health and Human Services/Centers for Disease Control and Prevention
Recommendations and Reports

incident cases of acute HBV infection in Kentucky, Tennessee, of the estimated 1.89 million persons (range = 1.49–2.40 million)
and West Virginia were among persons who reported IDU as chronically infected with HBV living in the United States,
a risk factor (25). 0.42 million (range = 0.28–0.67 million) were U.S. born
During 2019, the overall rate of reported acute infections and 1.47 million (95% CI = 1.21–1.73) were non-U.S. born
in the United States was 1.0 per 100,000 population. The (6,26). By region, the highest proportions of persons with
rate of reported acute HBV infections among persons aged chronic HBV infection in the United States were born in
0–19 years has remained at ≤0.1 case per 100,000 population East Asia, Southeast Asia, the Caribbean, South Central Asia,
since 2006, in part because of routine childhood vaccination and West Africa (6).
(23). However, transmission of HBV infection persists among From 2011 to 2017, the percentage of chronic HBV
adults, especially among older adults for whom vaccine uptake infection among women of childbearing age who were tested
is suboptimal. for HBV infection increased in Kentucky (from 0.2% to 0.4%),
Rates of acute HBV infection were higher among males Mississippi (from 0.2% to 0.4%), and West Virginia (from
(1.3 per 100,000 population) than females (0.7) and were 0.3% to 0.4%) (24). In 2019, the rate of newly reported cases
highest among not Hispanic or Latino (non-Hispanic) White of chronic HBV infection among adults varied by age, with
(1.0) persons and non-Hispanic Black persons (0.9). Among the highest rate (11.3 per 100,000 persons) reported among
the 1,780 case reports that included risk information for IDU, persons aged 30–39 years and the lowest rate (0.5) reported
35% reported IDU (23). Among the 1,042 case reports that among persons aged 0–19 years (23). During 2015–2017,
included sex partner data, 23% reported multiple sex partners. an estimated 20,678–21,314 infants were born to pregnant
Of the 2,009 case reports that included any risk information, women who were HBsAg positive (27). National Perinatal
47% had no risk identified. Hepatitis B Prevention Program data indicated that only half
(52.6%) of these infants were identified through prenatal
Chronic HBV Infection screening in 2017.
Data from the National Health and Nutrition Examination During 2019, a total of 1,662 deaths attributable to
Survey (NHANES) indicated an estimated 880,000 persons HBV infection in the United States were reported on death
were living with chronic HBV infection during 2013–2018 certificates, resulting in an age-adjusted rate of 0.42 per
(95% CI = 580,000–1,170,000) (5). The prevalence of resolved 100,000 persons (95% CI = 0.40–0.44) (23). The highest
HBV infection or HBV infection was 11.7 million persons death rates occurred among Asian and other Pacific Islander
(95% CI = 10.2–13.5 million). NHANES does not include persons (2.10), males (0.66), and persons aged 65–74 years
institutionalized populations and might underestimate the (1.54). However, deaths attributable to HBV infection have
prevalence among ethnic minority groups that are not well been found to be underreported on death certificates (1).
represented in the survey. In a 2018 meta-analysis of prevalence,

TABLE 1. Interpretation of screening test results for hepatitis B virus infection and recommended actions
Clinical state HBsAg Anti-HBs Total anti-HBc* IgM anti-HBc Action†
Acute infection Positive Negative Positive Positive Link to HBV infection care
Chronic infection Positive Negative Positive Negative§ Link to HBV infection care
Resolved infection Negative Positive Positive Negative Counsel about HBV infection reactivation risk
Immune (immunity inferred Negative Positive¶ Negative Negative Reassure if history of HepB vaccine series
from receipt of previous completion; if partially vaccinated, complete
vaccination) vaccine series per ACIP recommendations
Susceptible, never infected Negative Negative** Negative Negative Offer HepB vaccine per ACIP recommendations
Isolated core antibody positive†† Negative Negative Positive Negative Depends on cause of positive result
Abbreviations: ACIP = Advisory Committee on Immunization Practices; anti-HBs = antibody to hepatitis B surface antigen; HBcAg = hepatitis B core antigen;
HBsAg = hepatitis B surface antigen; HBV = hepatitis B virus; HepB = hepatitis B; IgG = immunoglobulin G; IgM anti-HBc = immunoglobulin M antibodies to hepatitis B
core antigen; total anti-HBc = total antibody to hepatitis B core antigen.
* Total anti-HBc is a measure of both IgM and IgG antibodies to HBcAg.
† Source: Abara WE, Qaseem A, Schillie S, et al. Hepatitis B vaccination, screening, and linkage to care: best practice advice from the American College of Physicians
and the Centers for Disease Control and Prevention. Ann Intern Med 2017;167:794–804.
§ IgM anti-HBc also might be positive in persons with chronic infection during severe HBV infection flares or reactivation.
¶ Immune if anti-HBs concentration is >10 mIU/mL after vaccine series completion.
** Anti-HBs concentrations might wane over time among vaccine responders (Source: Schillie S, Vellozzi C, Reingold A, et al. Prevention of hepatitis B virus infection
in the United States: recommendations of the Advisory Committee on Immunization Practices. MMWR Recomm Rep 2018;67[No. RR-1]:1–31).
†† Can be the result of a past infection when anti-HBs levels have waned, occult infection, passive transfer of anti-HBc to an infant born to an HBsAg-positive gestational
parent, a false positive, or mutant HBsAg strain that is not detectable by laboratory assay.

US Department of Health and Human Services/Centers for Disease Control and Prevention MMWR / March 10, 2023 / Vol. 72 / No. 1 3
Recommendations and Reports

FIGURE 1. Typical serologic courses of acute and chronic hepatitis B virus infection

A. Typical serologic course of acute HBV infection to recovery


HBV DNA
Symptoms
HBeAG Anti-HBe
Relative concentration

HBsAg
Total anti-HBc
IgM anti-HBc
Anti-HBs

0 4 8 12 16 20 24 28 32 36 52 100
Weeks after exposure

B. Typical serologic course of progression to chronic HBV infection


HBV DNA

Acute (6 months) Chronic (years)


HBeAG Anti-HBe
Relative concentration

HBsAg
Total anti-HBc
IgM anti-HBc

0 4 8 12 16 20 24 28 32 36 52
Weeks after exposure Years

Source: Adapted from Weinbaum CM, Williams I, Mast EE, et al.; CDC. 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.
Abbreviations: 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 = hepatitis B virus; IgM = immunoglobulin M.

4 MMWR / March 10, 2023 / Vol. 72 / No. 1 US Department of Health and Human Services/Centers for Disease Control and Prevention
Recommendations and Reports

Methods CDC solicited nominations for reviewers from AASLD, the


Infectious Disease Society of America, and the American
This report updates and expands CDC recommendations College of Physicians (ACP). Five clinicians with expertise in
for hepatitis B screening of adults published in 2008 hepatology, gastroenterology, internal medicine, or infectious
(14). CDC evaluated the addition of a universal screening diseases provided structured peer reviews and any edits made
recommendation among adults as well as testing persons in response were documented (Supplementary Appendices 2
expected to be at increased risk for HBV infection that were and 3, https://stacks.cdc.gov/view/cdc/124432). No CDC
not included in the 2008 testing recommendations. staff or external peer reviewers reported a conflict of interest.
Members of the CDC Guidelines Work Group (hereafter In addition, feedback from the public was solicited through a
referred to as the work group) followed CDC guideline Federal Register notice announcing the availability of the draft
development and reporting standards (28) to develop recommendations for public comment from April 4 through
research questions needed to assess the proposed updates; June 3, 2022. CDC received 28 public comments on the
conduct systematic reviews; assess the quality of the evidence; draft document from nonprofit/advocacy groups, providers,
and review existing systematic reviews, meta-analyses, and industry groups, medical professional organizations, the public,
cost-effectiveness analyses, when available (Supplementary academia, and a consulting group. Public comments were
Appendix 2; Supplementary Tables 1, 4, and 7, https:// considered by the work group and any edits made in response
stacks.cdc.gov/view/cdc/124432). Comprehensive systematic were documented (Supplementary Appendix 4, https://stacks.
literature reviews were conducted for recommendations on cdc.gov/view/cdc/124432).
1) expanding screening to all adults (i.e., universal screening), The work group also presented these guidelines to the
2) periodic testing for HBV infection among persons with CDC/Health Resources and Services Administration (HRSA)
hepatitis C virus (HCV) infection, and 3) testing for HBV Advisory Committee on HIV, Viral Hepatitis and STD
infection among persons with a history of incarceration. Prevention and Treatment, but did not seek consensus decision-
For all three systematic reviews, literature searches were making from this advisory committee. The steering committee
conducted by CDC librarians with direction from subject considered results of the systematic reviews in conjunction with
matter experts. Searches were conducted for English- cost-effectiveness analyses, supplemental literature, practicality
language literature published worldwide in Medline of implementing guidelines, public health benefits, subject
(OVID), Embase (OVID), CINAHL (Ebsco), and Cochrane matter expertise, and reviewer and public feedback.
Library. Duplicates were identified and removed using
Endnote (version 20; Clarivate Analytics) and DistillerSR
systematic review software (version 2.35; Evidence Partners) Systematic Review Methods
automated “find duplicates” functions. Universal Screening
CDC’s Viral Hepatitis Steering Committee considered
multiple methods to assess quality of evidence. The Mixed The search period was January 1, 2008 (the year of the
Methods Appraisal Tool (MMAT) was selected because it last CDC screening guidelines) through February 8, 2021
is a validated tool for assessing nonrandomized analytic and (Supplementary Table 2, https://stacks.cdc.gov/view/
descriptive studies, which comprise most of the HBV infection cdc/124432). Search results were supplemented by relevant
prevalence literature (29). MMAT users rate each study on studies identified through reference lists in review articles and
methodological quality criteria, indicating whether criteria were by newly published studies. DistillerSR was used to organize
met with “Yes,” “No,” or “Can’t Tell.” Calculating a summary the review process. Each article was reviewed for inclusion by
score is not recommended for the tool because presenting a single two of the authors (EC and LP). Differences in decisions to
number is not informative about which aspects of the studies include were discussed until consensus was reached. Articles were
are problematic. Economic analyses were evaluated by assessing included if they contained the prevalence or incidence of HBV
whether the study met the Consolidated Health Economic infection among adults aged ≥18 years or linkage-to-care data.
Evaluation Reporting Standards (CHEERS) (30). Articles were excluded if they were conducted outside the United
CDC determined that the new recommendations constituted States and U.S. territories; only reported data from a study not
influential scientific information that will have a clear and conducted in humans, environmental studies, or technology
substantial impact on important public policies and private assessments; lacked original data (e.g., editorials, reviews, and
sector decisions. Therefore, the Information Quality Act modeled data); were case reports; or only included self-reported
required peer review by specialists in the field who were not (i.e., unconfirmed) HBV infection prevalence (Supplementary
involved in the development of these recommendations. Table 3, https://stacks.cdc.gov/view/cdc/124432). When a

US Department of Health and Human Services/Centers for Disease Control and Prevention MMWR / March 10, 2023 / Vol. 72 / No. 1 5
Recommendations and Reports

reviewer identified an article as meeting any exclusion criterion, Universal Screening


additional exclusion criteria were not assessed or recorded.
When multiple articles reported data on the same cohort, only Systematic Review and Review of
the article with the most complete data was included. Data Evidence Summary
were independently abstracted by two reviewers (EC and LP) After deduplication, 2,580 records were available for initial
and discrepancies were discussed until consensus was reached title screen; 1,374 articles were excluded during title screen.
or they were resolved by a third reviewer (NN). Finally, two An additional 1,028 articles were excluded during abstract
independent assessors (LP, JB, or NN) used MMAT to assess review. Among the 178 full text articles, 136 did not meet
the quality of articles used to calculate the prevalence of HBV inclusion criteria after review; 42 articles were included in the
infection in the general population. final review (Supplementary Table 11, https://stacks.cdc.gov/
Persons with HCV Infection view/cdc/124432). An additional article met inclusion criteria,
but was published after the search period, and was abstracted
The search period was January 1, 2005 through
to supplement evidence from the systematic search.
September 22, 2020 (Supplementary Table 5, https://stacks.
Eighteen articles had any HBV testing data from the general
cdc.gov/view/cdc/124432). DistillerSR and Endnote were used
population (i.e., screening persons not known to be at increased
to organize the review process. Titles were reviewed by one
risk for HBV infection) (Supplementary Table 11, https://
reviewer (PS or EC), and those that were clearly irrelevant to
stacks.cdc.gov/view/cdc/124432). Testing recommendations
the research question were excluded. Each potentially relevant
are risk based; therefore, studies with convenience samples
article was reviewed for inclusion by two of the authors (MH
of persons already tested for HBV infection were considered
and PS). Differences in decisions to include were discussed
biased toward overestimating the prevalence of HBV infection
until consensus was reached (Supplementary Table 6, https://
even if the study did not explicitly state that there was risk-based
stacks.cdc.gov/view/cdc/124432). Data from the included full
testing. The remainder of the articles (n = 25) included persons
text articles were independently abstracted by two reviewers
at increased risk for HBV infection who were not considered to
(MH, PS, or EC). The quality of the articles was assessed using
be representative of the general U.S. population. The individual
MMAT. The population was considered at “increased risk” if
MMAT quality ratings are available (Supplementary Tables 14
the prevalence of HBV infection was ≥1%.
and 15, https://stacks.cdc.gov/view/cdc/124432).
Persons with a History of Incarceration in a Jail,
Prison, or Other Detention Setting Key Research Questions
The work group used an existing literature search of articles
Q1: How would adult universal screening for
on HBV and HCV infections in correctional and detention
hepatitis B affect the number (and composition)
facilities. The search period was January 1, 2000 through
of persons who screen positive for HBV infection?
March 3, 2021 (Supplementary Table 8, https://stacks.cdc.gov/
view/cdc/124432). Abstracts were reviewed by two reviewers
Q1a: What is the prevalence of chronic HBV infection
(AH, LH, JB, OR, or EC) for relevance, and discrepancies
in the United States? In the general population, by
in inclusion were resolved by the first author (EC) or by
age groups?
consensus discussion. Only articles containing incidence or
prevalence of HBV infection among persons with a history of The work group defined patients who have chronic HBV
incarceration or incarceration as a risk factor for HBV infection infection as those who were HBsAg positive, except for one
were included in this review (Supplementary Table 9, https:// study in which authors classified patients as having chronic
stacks.cdc.gov/view/cdc/124432). Data from the included HBV infection without providing a definition. Studies among
full text articles or abstracts were independently abstracted first-time blood donors, organ donors, pregnant women
by two reviewers (LP and EC) and differences were resolved (among whom universal screening is already recommended),
by consensus discussion. Because of the limited amount NHANES enrollees, and patients seeking care for a condition
of literature available about HBV infection in correctional other than HBV infection were included.
settings, the work group included conference abstracts, which On the basis of 17 studies conducted both in the
are labeled as such because of their presumed lower quality. United States and U.S. territories, the median prevalence of
The quality of the articles was assessed using MMAT. The chronic HBV infection in the general population was 0.4%
population was considered at “increased risk” if the prevalence (range = 0.0%–2.0%) (Supplementary Table 11, https://
of HBV infection was ≥1%. stacks.cdc.gov/view/cdc/124432). On the basis of studies

6 MMWR / March 10, 2023 / Vol. 72 / No. 1 US Department of Health and Human Services/Centers for Disease Control and Prevention
Recommendations and Reports

conducted in the United States alone, the prevalence was The diagnostic accuracy of HBV tests has been evaluated
0.38% (range = 0%–0.74%) (Supplementary Table 11, https:// by the Food and Drug Administration (FDA) and was
stacks.cdc.gov/view/cdc/124432). Eight studies reported the not included as part of the systematic review. Any assay
prevalence of a history of infection (i.e., anti-HBc positive, HBsAg that receives FDA approval for clinical use must meet high
negative); the median was 6.2% (range = 4.8%–14.0%) (31–38). standards of diagnostic accuracy. A list of FDA-approved HBV
The ages of patients with chronic HBV infection (when serologic assays, including links to detailed information on
available) are included in the summary table (Supplementary their performance characteristics, is available (Supplementary
Table 11, https://stacks.cdc.gov/view/cdc/124432). No clear Table 21, https://stacks.cdc.gov/view/cdc/124432).
trends were identified in the prevalence of chronic HBV Q2b: What are the harms of hepatitis B screening?
infection by age across studies. Therefore, the work group
considered the economic analysis, vaccination rates and Data on harms in the systematic review were limited. In one
efficacy, the epidemiology of acute and chronic infections study, women with public insurance and who self-paid for
from surveillance data, ease of implementation, and harms of health care services were less likely to be screened, even though
missed identification of chronic infections in determining the HBsAg screening costs should have been covered; the authors
age thresholds for universal adult screening. hypothesized that out-of-pocket payments might be a barrier
Q1b: What is the yield (number of new diagnoses per to screening (45). In another study assessing acceptability
tests completed) and sensitivity of alternative of hepatitis screening among patients during colonoscopies,
HBV screening strategies (e.g., universal versus acceptance was 78% (46).
targeted screening or screening strategies based on Harms of screening for HBV would be expected to be
alternative risk factors)? similar to those for HCV. In a previous review, possible
harms of screening for hepatitis C were physical pain, anxiety,
As part of their HBV screening recommendations systematic cost, interpersonal problems related to learning infection
review, the U.S. Preventive Services Task Force (USPSTF) assessed status, stigma, time, fear, and reluctance to disclose illegal
the yield (number of new diagnoses per tests completed) and risk behaviors (47). Other plausible harms included concern
sensitivity of alternative HBV infection screening strategies (39). caused by false-positive results, distress resulting from lack of
USPSTF identified three fair quality, non-U.S.–based studies, education or understanding of resolved infection, insurability
which might limit applicability (40–42). On the basis of these and employment issues, and treatment adverse effects.
studies, the number of persons who need to be screened to identify The work group concluded that potential harms of screening
one HBV infection using risk-based strategies ranged from 32 to did not outweigh the benefits. In addition, universal screening
148. In comparison, fewer than 20 persons need to be screened to might reduce harms compared with risk-based screening by
identify a case of HCV infection using risk-based screening (43). not requiring persons to disclose potentially stigmatizing risk
Only one of the studies, conducted in France, assessed conditions (e.g., immigration status and IDU) to get tested.
CDC’s risk-based testing criteria (41). Using risk-based testing Q2c: What proportion of persons who screen positive for
had 100% sensitivity (i.e., 100% of infected persons were HBV infection are linked to care?
identified), and self-report identified 70% of persons with at
least one risk factor; however, the study population specifically Q2d: What proportion of persons who screen positive for
overrepresented persons at increased risk for infection. HBV infection are treatment eligible?
The work group also considered a prospective cohort study of
patients with cancer at one U.S. health center, where applying Q2e: What proportion of eligible persons who screen
CDC risk criteria to screening had 97% sensitivity (44). The positive for HBV infection are treated?
proportion of patients who met at least one risk criterion was 91%.
Therefore, in terms of provider time, universal screening might be Only two studies from the universal screening review
more efficient than risk-based testing. Because no studies directly reported on linkage to care. In a study among persons
assessed universal screening, the work group could not provide the attending free clinics, 69% of patients with a diagnosis of
yield of universal screening versus risk-based screening. chronic HBV infection enrolled in follow-up care (48).
Q2: How many additional persons would be linked In a free screening clinic, 78% of patients with HBV
to care? infection elected to undergo follow-up monitoring (i.e.,
alanine aminotransferase [ALT]) and HBV DNA), and 24%
Q2a: What is the diagnostic accuracy of HBV testing? (11 of 45) of those monitored were eligible for treatment
(i.e., viral load of >20,000 copies per mL) (49).

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Recommendations and Reports

Data on treatment were only available in two studies of HBsAg positive, and 30% had a history of infection
antiviral treatment during chemotherapy. In one study, 23% (anti-HBc positive) (55). In 2019, surveillance data indicated
of patients at risk for reactivation were prescribed a preventive that 10% (92 of 899) of persons with acute cases had a sexual
nucleoside analog (50). In the other study, 12% (18 of 152) of contact and 2% (17 of 899) had a nonsexual household contact
patients with a previous HBV infection received antiviral drugs, (23). However, relying on self-reports of close contacts with
and 73% (11 of 15) of patients with chronic HBV infection HBV infection likely underestimates the risk. Global studies
received antiviral drugs (36). conducted during 1974–2007 found that 14%–60% of
To answer these key questions, the work group also assessed persons living in households with persons with chronic HBV
evidence from two additional studies that were not part of the infection have serologic evidence of resolved HBV infection,
systematic review but included the general population. In a and 3%–30% have chronic infection (14). Although screening
2008–2016 study of adults with chronic HBV infection and can prevent further spread of HBV infection, the work group
commercial insurance, 36% (6,004 of 16,644) of patients were was unable to estimate the size of that impact.
linked to care (defined as having had an ALT test and HBV Q4: Do desirable management and treatment effects
DNA or HBeAg test) (51). Of the patients with chronic HBV outweigh undesirable effects?
infection with prescription claims, 18% (2,926 of 16,572) were
treated. Among 2,338 patients with chronic HBV infection Key Q4 was not assessed by the systematic review because it
followed in a prospective cohort study, 78% had one or more has been reported elsewhere. USPSTF reviewed effectiveness
ALT tests annually, 37% had one or more HBV DNA tests of treatment on reducing viral load, HBeAg, HBsAg, cirrhosis,
annually, and 32% were treated (52). Not all patients with hepatocellular carcinoma (HCC), and death (39). Antiviral
chronic HBV infection require treatment; estimates of patients therapy was associated with viral suppression, HBsAg loss,
with HBV infection meeting AASLD criteria for treatment normalization of ALT levels, and HBeAg loss. Antiviral
range from 24% to 48% (53,54). These two studies did not therapy was associated with decreased risk for HCC and death
assess the proportion of persons treated among those who were compared with placebo or no therapy; however, data were
eligible. Overall, the work group found that linkage-to-care sparse and estimates imprecise. Therapy was not associated
rates ranged from 36% to 78%, and from 18% to 32% of with an increased risk for serious adverse events. The conclusion
patients with chronic HBV infection were prescribed treatment. of AASLD’s systematic review used in the development of
Q3: How many new infections of HBV would its treatment guidelines was that recommended treatment
be prevented? reduces cirrhosis, decompensated cirrhosis, HCC, and death
in adults with active chronic HBV infection and is strongly
Q3a: What proportion of close contacts are at risk recommended (10).
for infection?

The work group did not identify evidence directly assessing the Cost-Effectiveness
proportion of close contacts (excluding perinatal transmission)
who are at risk for infection and thus could not estimate the
of Screening Strategies
proportion of new infections that would be prevented by Universal Screening
universal adult screening. However, the work group found
A 2021 economic analysis on the cost-effectiveness of
evidence of the proportion of close contacts of persons with
one-time universal HBV screening of adults aged 18–69 years
HBV infection who themselves have HBV infection.
provided information for these guidelines (56). With an
From the systematic review, a cohort study of patients with
estimated prevalence of undiagnosed chronic HBV infection
cancer and previous HBV infection found that 8.1% reported
of 0.24%, universal HBsAg screening among adults
having a household contact with HBV infection (who was
aged 18–69 years was cost-saving compared with current
not a sex partner), and 15.2% reported sexual contact with
practice, assuming antiviral treatment drug costs remain at
a person with HBV infection. Of the patients with chronic
<$894 per year. Antiviral treatment drug costs would need to
HBV infection, 0.5% reported a nonsexual household contact
rise to $9,692 a year (approximately 19 times the cost at the
with HBV infection, and 1.5% reported sexual contact with a
time of the study) for universal screening to be no longer cost-
person with HBV infection (36).
effective. Undiagnosed prevalence was based on the NHANES
In a study of programs testing and linking patients with
estimate of 0.36% and the finding that 67% of persons with
hepatitis B to care in the United States, 14% of household
HBV infection were unaware of their infection (57). Current
contacts of persons who were HBsAg positive were themselves

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practice was based on the literature and assumed that 33% of it identified persons with previous vaccination and averted the
persons with HBV infection were currently diagnosed, 36% cost of additional vaccine doses.
were linked to care, and 18% were receiving treatment (56).
Compared with current practice, universal screening would
be expected to avert an additional 7.4 cases of compensated Universal Screening Summary
cirrhosis, 3.3 cases of decompensated cirrhosis, 5.5 cases of
HCC, 1.9 liver transplants, and 10.3 HBV-related deaths per
of Findings
100,000 persons screened (56). Universal HBsAg screening The steering committee considered results of the systematic
of adults aged 18–69 years would save $262,857 per quality- review in conjunction with cost-effectiveness analyses,
adjusted life year (QALY) and would result in a gain of supplemental literature, practicality of implementing
135 QALYs per 100,000 adults screened. A probabilistic guidelines, public health benefits, subject matter expertise,
sensitivity analysis that varied all parameters in the model and reviewer and public feedback. Because of limited data,
simultaneously indicated a >99% likelihood that universal the steering committee was only indirectly able to assess
screening would be cost-effective compared with current the key question “How would adult universal screening for
practice at a maximum willingness-to-pay threshold of hepatitis B affect the number [and composition] of persons
$50,000 per QALY. who screen positive for HBV infection?” A summary of
Study authors conducted an unpublished analysis using the the evidence considered, rationale for screening (Box 2),
same methods as those in the economic analysis described in conclusions of the steering committee, and limitations is
this report, but with an upper age limit of 80 years instead available (Supplementary Table 10, https://stacks.cdc.gov/
of 69. They found one-time universal screening of adults aged view/cdc/124432). The steering committee concluded that
18–80 years with an HBsAg test would save $200,334 and simplifying the implementation of screening from a risk-
result in a gain of 128 QALYs per 100,000 adults screened. based to a universal approach might increase the number of
A sensitivity analysis found that using the triple panel persons aware of their infection. Overall, risk-based testing
(HBsAg, anti-HBc, anti-HBs) and assuming Medicare has been insufficient to identify persons with HBV infection
reimbursement of $28.27, universal screening with the in the United States and has been a barrier to appropriately
triple panel would be cost-effective, with an incremental screening populations with a disproportionate prevalence of
cost-effectiveness ratio of $11,207 per QALY (56). Using a disease. Assessment of risk is difficult for providers and might
cost-effectiveness threshold of $50,000 per QALY, universal be stigmatizing to the patient.
screening with the triple panel remained cost-effective if the A one-time HBV screening of adults would be complementary
HBV infection prevalence was >0.15%. A summary of the to the 2022 Advisory Committee on Immunization Practices
CHEERS checklist is available (Supplementary Table 20,
https://stacks.cdc.gov/view/cdc/124432). Minor deviations BOX 2. Rationale for universal hepatitis B virus screening
from the recommended standards were not considered a
• Hepatitis B virus (HBV) infection has substantial
substantial risk to quality.
morbidity and mortality.
• Chronic HBV infection can be detected before the
Screening in Higher Prevalence Settings development of severe liver disease using reliable and
A 2022 cost-effectiveness analysis evaluated whether inexpensive screening tests.
screening in STI clinics (i.e., a high-prevalence setting) with • Treatment for chronic HBV infection can reduce
universal vaccination can reduce costs and improve care (58). morbidity and mortality.
The researchers assumed the study population was aged • Management of chronic HBV infection might
18–69 years, had an estimated HBsAg prevalence of 4.2%, prevent transmission to others.
and had no previous HepB vaccination or known HBV • Universal screening of adults is cost-effective.
infection. One-time screening with the triple panel was cost- • Screening enables identification and management of
saving and prevented an additional 138 cases of cirrhosis, pregnant persons infected with HBV and their infants,
47 cases of decompensated cirrhosis, 90 cases of HCC, 33 which can reduce the risk for perinatal transmission.
liver transplants, and 163 HBV-related deaths per 100,000 • Screening can identify persons who are at risk for
adults screened. Even if chronic HBV infection prevalence in reactivation of HBV infection.
the STI clinic population was assumed to be zero, screening • Screening might identify persons who would benefit
plus vaccination was less costly than vaccination alone because from hepatitis B vaccination.

US Department of Health and Human Services/Centers for Disease Control and Prevention MMWR / March 10, 2023 / Vol. 72 / No. 1 9
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(ACIP) recommendation to vaccinate all adults aged risk for HBV reactivation was 24% (95% CI = 19%–30%)
19–59 years for HBV infection because screening establishes in patients with untreated chronic HBV infection and 1.4%
any history of infection, and vaccination protects from (95% CI = 0.8%–2.4%) in patients with resolved HBV
future infection and need for additional testing (59). The infection (72). The risk for HBV reactivation–related hepatitis
recommendations were supported by peer reviewers who are (i.e., symptomatic) was 9% (95% CI = 5%–16%) in patients
experts in the field as well as the majority of public comments. with chronic HBV infection; HBV reactivation–related
Patients with HBV infection have increased morbidity and hepatitis did not occur in patients with resolved infection.
mortality, and monitoring and treatment can improve health Three of 1,621 patients with chronic HBV infection had
outcomes. If more efficacious treatments are approved in the a major clinical event related to the reactivation (liver
future, this benefit will increase further. Although increasing decompensation or failure), but there were no deaths.
awareness of infection is expected to reduce transmission to Four studies (62,69,73,74) were published after the 2018
close contacts, this assumption is hypothetical because of the systematic review (72). In two national cohort studies of U.S.
lack of direct evidence. No studies directly compared universal veterans with chronic HCV infection prescribed DAA therapy,
screening with risk-based screening; therefore, the steering HBV reactivation was rare (<0.1%) and more frequent among
committee relied on the cost-effectiveness study finding that a patients who were HBsAg positive (62,73). Similarly, two other
one-time universal screen of adults is cost-effective and results U.S.-based cohort studies of patients with HCV coinfected
in improved health outcomes as compared with risk-based with HBV did not detect any cases of DAA-associated HBV
screening (56). reactivation (69,74).
Outcomes of HCV/HBV Coinfection
Persons with an Increased Risk for HBV In a study comparing patients with HCV infection
Infection Recommended for Testing achieving sustained virologic response to HCV treatment,
Persons with HCV Infection or anti-HBc positivity was identified as an independent risk
factor for the development of HCC (hazard ratio [HR] = 5.57;
a Past HCV Infection
95% CI = 1.45–21.39) (75). Conversely, a nested, case-
The systematic review found 8,295 articles for review; after control study of patients who were HBsAg negative with
title review, 1,233 potentially relevant articles remained. After HCV infection indicated that neither previous nor occult
review of articles meeting inclusion and exclusion criteria, HBV infection was associated with the development of
17 articles were included (Supplementary Table 12, https://stacks. HCC (76). Clinically significant hepatic events, including
cdc.gov/view/cdc/124432). In 10 U.S. studies, the prevalence of HBV reactivation, were more common among patients
current HBV infection (on the basis of HBsAg positivity, HBV who were cirrhotic than patients who were noncirrhotic
DNA positivity, or International Classification of Diseases, Tenth anti-HBc positive with chronic HCV infection undergoing
Revision codes) among persons with HCV infection ranged DAA therapy (73). Among a cohort of 51,781 veterans who
from 0.2% to 5.8% (median = 1.2%) (60–69). Among persons were HCV infected and who initiated DAA treatment, those
with HCV infection, the prevalence of ever being exposed to who were HBV/HCV coinfected (odds ratio [OR] = 2.25;
HBV ranged from 24.7% to 62.6% (median = 43.0%); this 95% CI = 1.17–4.31) and those with resolved HBV infection
finding was based on anti-HBc positivity, regardless of other (OR = 1.09; 95% CI = 1.03–1.15) were more likely to achieve
HBV test results (62–65,69,70). Isolated anti-HBc positivity sustained virologic response compared with patients who were
ranged from 36.9% to 53.8% (median = 39.5%) among HCV monoinfected (64).
patients with HCV infection (62,65,69). In a national cohort of 99,548 U.S. veterans, patients
HBV Reactivation During Direct-Acting Antiviral with HCV infection and documented HBV viremia
Therapy for HCV (HBV DNA detected) were at significantly higher risk for cirrhosis
(adjusted hazard ratio [aHR] = 1.89; 95% CI = 1.46–2.45),
FDA requires a boxed warning about the risk for HBV
HCC (aHR = 2.12; 95% CI = 1.26–3.60), and death
reactivation to be added to drug labels of direct-acting antiviral
(aHR = 1.62; 95% CI = 1.33–1.99) than patients who
(DAA) medication for HCV infection. The boxed warning
were HCV monoinfected, after controlling for demographic,
directs health care professionals to screen and monitor for
clinical, and antiviral treatment–related factors (68). In this
HBV infection in all patients receiving DAA treatment (71).
cohort, absence of HBV replication was associated with a
In a published systematic review of HBV reactivation during
clinical course similar to that of patients who were HCV
DAA therapy among patients with HCV infection, the overall
monoinfected. Compared with patients who were HCV

10 MMWR / March 10, 2023 / Vol. 72 / No. 1 US Department of Health and Human Services/Centers for Disease Control and Prevention
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monoinfected, patients with HBV/HCV coinfection had more Three studies found an increased risk for HBV infection
advanced fibrosis, a faster fibrosis progression rate, and more associated with incarceration. In a study of blood donors,
severe steatosis (63). In a matched case-control study, patients persons detained ≥3 nights in a jail or detention facility had
with HBsAg-negative HCV infection with HCC were more three times higher odds of having serologic evidence of HBV
likely to have had previous HBV infection (anti-HBc positive), infection; however, the comparison group was not provided
regardless of anti-HBs status (anti-HBs negative [OR = 2.98; (p≤0.001) (86). In another study, persons incarcerated
95% CI = 2.12–5.08]; anti-HBs positive [OR = 1.84; >14 years had 1.68 (95% CI = 1.08–2.59) higher odds of ever
95% CI = 1.22–3.08]), compared with HCV-infected controls acquiring HBV infection compared with those incarcerated
without HCC (77). ≤7 years (81). Finally, a third study indicated that persons
Many studies had incomplete test data and used descriptive with any self-reported history of incarceration had increased
tests of significance rather than models that controlled for other odds (OR = 1.84; 95% CI = 1.02–3.31) of ever having
variables. The results from the MMAT quality assessment are HBV infection compared with persons with no history of
available (Supplementary Tables 18 and 19, https://stacks. incarceration (87).
cdc.gov/view/cdc/124432). The work group concluded that The work group determined that persons incarcerated or
because the prevalence estimate was ≥1% for HBV infection formerly incarcerated in a jail, prison, or other detention setting
and because of the boxed warning for DAAs, persons with should be considered at increased risk. This conclusion was
HCV infection or a past HCV infection should be considered based on the HBV infection prevalence estimate of ≥1% and
at increased risk for HBV infection. the studies directly indicating an association between HBV
infection and incarceration. The reasons for increased risk for
Persons Incarcerated or Formerly Incarcerated in HBV infection among persons who have been incarcerated
a Jail, Prison, or Other Detention Setting might include behaviors that occur before or during
The systematic review of HBV infection in correctional incarceration, including drug use, higher-risk sex, percutaneous
settings used for these testing guidelines was part of a larger exposures (e.g., tattooing), and structural factors that affect the
review that also contained articles on HCV infection in level of risk for these behaviors (e.g., availability of condoms,
correctional settings (“review 1”). The initial search of literature clean syringes, and engagement in health care). To ensure
on HBV infection and HCV infection in correctional settings all incarcerated persons receive recommended HBV testing,
yielded 2,395 unique articles for review; of these, 1,961 were correctional and detention facilities should consider offering
deemed irrelevant by title and abstract screening, resulting HBV screening at intake, periodic testing for susceptible
in 434 potential articles for review 1. A secondary abstract persons serving long-term sentences, and HepB vaccination
review (“review 2”), which applied the inclusion and exclusion for susceptible persons (16).
criteria for these guidelines, resulted in 57 articles that met
the inclusion criteria for full text review; three of these Persons with Sexually Transmitted Infections or
articles also were included in the HBV universal screening a History of Sexually Transmitted Infections or
systematic review. After full text review, 10 articles were Multiple Sex Partners
included (Supplementary Table 13, https://stacks.cdc.gov/ The work group used a published systematic review and
view/cdc/124432). The individual MMAT quality ratings are meta-analysis to assess risk among persons with a history
available (Supplementary Tables 16 and 17, https://stacks.cdc. of a non-HIV sexually transmitted infection (STI) (88).
gov/view/cdc/124432). This analysis of studies worldwide found positive and
Among eight studies, the prevalence of chronic HBV statistically significant associations between the prevalence
infection in persons with a history of incarceration ranged of HBV infection and other STIs. Three U.S. studies,
from 0.6% to 8.7% (median = 1.0%) (78–85). Two studies of published during 2008–2009, included four estimates of
men who were incarcerated assessed incidence, which ranged HBsAg prevalence among persons with syphilis or any STI;
from 2,700 to 3,579 infections per 100,000 persons per year the median prevalence was 1.6% (range = 0.9%–33.2%).
(78,81). One study reported 41 acute HBV infections acquired Among the four estimates, two were among groups with other
in prison; however, the total number tested was not reported risk factors for HBV infection (e.g., persons being processed
and therefore a prevalence or incidence rate could not be into jail and men who have sex with men [MSM]). Seven
calculated (85). Another study reported an infection rate of U.S. studies, published during 1998–2000, included nine
1.2% during an outbreak of HBV infection in a high-security estimates of prevalence of HBV infection or a history of HBV
correctional facility (83). infection (HBsAg or anti-HBc positive) among persons with

US Department of Health and Human Services/Centers for Disease Control and Prevention MMWR / March 10, 2023 / Vol. 72 / No. 1 11
Recommendations and Reports

STIs or a history of STIs; the median prevalence was 22.4% Persons Who Use Injection Drugs or Have a
(range = 8.6%–83.5%). Among the nine estimates of past History of IDU
infection, four were among groups with other risk factors for
A systematic review estimated the prevalence of HBV
HBV infection (e.g., persons who use drugs, persons with HIV
infection among persons who use injection drugs to be 11.8%
infection, and MSM).
(range = 3.5%–20%) and ever having had an infection to be
A study of national surveillance reports and survey data during
22.6% (93). Transmission of HBV among persons who use
2013–2018 found 1,324 (38.2%) cases of sexually transmitted
injection drugs might be increasing. A study of prevalence of
acute HBV infection after excluding cases with a report of
anti-HBc in national survey data found an increase among
IDU; 5.3% of persons reported sexual contact with a person
persons who use injection drugs from 35.3% during 2001–
with HBV infection, 3.1% reported being male and having sex
2006 to 58.4% during 2013–2018 (94).
with another male partner, 27.8% reported having multiple sex
partners, and 2% reported a history of STI treatment 6 weeks Persons with HIV Infection
to 6 months before their HBV infection diagnosis (89). Cases Multiple studies with varying inclusion criteria and periods
were classified into mutually exclusive categories in the order during 1986–2012 used prospective cohort data from the
listed. The work group considered the HBsAg prevalence of U.S. Military HIV Natural History Study (NHS) to calculate
>1% among persons with an STI to be sufficient evidence of the prevalence of HBV infection among persons with HIV
increased risk. Although the recommendation for multiple infection. Among patients in NHS, coinfection ranged from
partners is not directly supported by the literature, it aligns 3.0% to 6.0% (95–97). In a large prospective cohort study
with AASLD recommendations to screen persons who are not of adults with HIV infection, annual chronic HBV infection
in a long-term, mutually monogamous relationship (i.e., more prevalence during 1996–2007 ranged from 7.8% to 8.6% (98).
than one sex partner during the previous 6 months) (11).
MSM
Infants Born to Pregnant Persons Who Are
Among a sample of Los Angeles County, California, residents
HBsAg Positive
from the National HIV Behavioral Surveillance system,
Without preventive steps, 90% of infants born to women 19% (95% CI = 15%–24%) of MSM had HBV infection
who are HBsAg and HBeAg positive and 5%–20% of infants or a history of HBV infection, and 35% of the sample were
born to women who are HBsAg positive, HBeAg negative will coinfected with HIV (99). In a survey of MSM from six U.S.
become infected (90–92). Additional information is available metropolitan areas during 1998–2000, the prevalence of ever
in Prevention of Hepatitis B Virus Infection in the United States: infection was 20.6%, and 2.3% of participants had active
Recommendations of the Advisory Committee on Immunization HBV infection; HBV infection was independently associated
Practices (15) and from AASLD (11). with a history of another STI, having more lifetime partners,
Persons Born in Regions with HBV Infection ever engaging in anal intercourse, and ever using injection
drugs (100).
Prevalence of ≥2%
A 2021 systematic review and meta-analysis estimated the Household, Needle-Sharing, or Sexual Contacts
prevalence of non-U.S.–born persons with chronic HBV of Persons with Known HBV Infection
infection in the United States to be 3.1% (95% CI = 2.5%–3.6%). HBV is highly infectious and can survive in the environment
Africa had the highest regional prevalence (8.6%), followed by for prolonged periods. Close (i.e., household, needle-sharing,
Asia (5.9%) and Oceania (4.5%) (6) (Box 3). or sexual) contacts of persons with known HBV infection are
Persons Born in the United States Not Vaccinated at greater risk (see Universal Screening Systematic Review and
Review of Evidence Summary).
as Infants Whose Parents Were Born in Regions
with HBV Infection Prevalence of ≥8% Persons on Dialysis, Hemodialysis, or
The population of persons born in the United States who Peritoneal Dialysis
were not vaccinated as infants whose parents were born in A study during 1997–2001 of adult hemodialysis patients
regions with HBV infection prevalence of ≥8% is at increased found an adjusted prevalence of HBV infection of 2.4%
risk for infection. The higher underlying prevalence in this (95% CI = 2.1–2.7) (101). Dialysis was reported only in 3%
population increases the likelihood of perinatal or close contact (34 of 1,292) of 2,019 acute HBV infection cases; however,
exposures (Box 3). the risk for developing chronic infection was higher among

12 MMWR / March 10, 2023 / Vol. 72 / No. 1 US Department of Health and Human Services/Centers for Disease Control and Prevention
Recommendations and Reports

BOX 3. Prevalence of chronic hepatitis B virus infection, by country or territory

• High prevalence (≥8%): Angola, Cabo Verde, Central African Republic, Chad, Eswatini, Ghana, Guinea,
Guinea-Bissau, Kiribati, Lesotho, Liberia, Mali, Mauritania, Niger, Nigeria, Philippines, Sao Tome and Principe,
Sierra Leone, Solomon Islands, Taiwan, Timor-Leste, Togo, Tonga, Turkmenistan, Tuvalu, and Zimbabwe.
• Intermediate prevalence (5%–7.9%): Albania, Benin, Burkina Faso, Cameroon, China, Côte d’Ivoire,
Democratic People’s Republic of Korea, Djibouti, Eritrea, Ethiopia, Federated States of Micronesia, Gabon, Indonesia,
Kyrgyzstan, Moldova, Mongolia, Mozambique, Myanmar, Papua New Guinea, Senegal, Somalia, South Sudan, Syria,
Tajikistan, Uzbekistan, Vanuatu, and Vietnam.
• Low–intermediate prevalence (2%–4.9%): Afghanistan, Azerbaijan, Bangladesh, Belarus, Bosnia and Herzegovina,
Bulgaria, Burundi, Cambodia, Comoros, Congo, Democratic Republic of Congo, Gambia, Georgia, Guyana, Haiti,
Hong Kong, India, Iraq, Jamaica, Jordan, Kazakhstan, South Korea, Laos, Madagascar, Malawi, Malaysia,
Marshall Islands, Oman, Pakistan, Romania, Rwanda, Samoa, Singapore, South Africa, Sri Lanka, Sudan, Tanzania,
Thailand, Trinidad and Tobago, Tunisia, Turkey, Uganda, Yemen, and Zambia.
• Low prevalence (≤1.9%): Algeria, Argentina, Armenia, Australia, Austria, Bahrain, Belgium, Belize, Bhutan, Bolivia,
Brazil, Canada, Chile, Colombia, Costa Rica, Croatia, Cuba, Czechia, Denmark, Dominican Republic, Ecuador, Egypt,
El Salvador, Estonia, Fiji, Finland, France, Germany, Greece, Guatemala, Honduras, Hungary, Iran, Ireland, Israel, Italy,
Japan, Kenya, Kosovo, Kuwait, Lebanon, Libya, Mexico, Morocco, Nepal, Netherlands, New Zealand, Nicaragua,
Norway, Palestine, Panama, Paraguay, Peru, Poland, Portugal, Qatar, Russia, Saudi Arabia, Slovakia, Slovenia, Spain,
Suriname, Sweden, Switzerland, Ukraine, United Arab Emirates, United Kingdom, United States, and Venezuela.
• Unknown prevalence (data not available): American Samoa, Andorra, Anguilla, Antigua and Barbuda, Aruba,
Bahamas, Barbados, Bermuda, Bonaire Sint Eustatius and Saba, Botswana, British Virgin Islands, Brunei,
Cayman Islands, Cook Islands, Curaçao, Cyprus, Dominica, Equatorial Guinea, Falkland Islands, Faroe Islands,
French Guiana, French Polynesia, Gibraltar, Greenland, Grenada, Guadeloupe, Guam, Holy See, Iceland, Isle of Man,
Latvia, Liechtenstein, Lithuania, Luxembourg, Macao, Macedonia, Maldives, Malta, Martinique, Mauritius, Mayotte,
Monaco, Montenegro, Montserrat, Namibia, Nauru, New Caledonia, Niue, Northern Mariana Islands, Palau,
Puerto Rico, Réunion, Saint Barthélemy, Saint Helena, Saint Kitts and Nevis, Saint Lucia, Saint Martin,
Saint Pierre and Miquelon, Saint Vincent and the Grenadines, San Marino, Serbia, Seychelles, Sint Maarten, Tokelau,
Turks and Caicos Islands, U.S. Virgin Islands, Uruguay, Wallis and Futuna, and Western Sahara.

Source: Polaris Observatory [Internet]. Lafayette, CO: Center for Disease Analysis Foundation; 2021. https://cdafound.org/polaris

persons who are immunosuppressed and undergoing dialysis Rationale for New Recommendations
than persons who are immunocompetent (23,102,103).
Recommendations for Preventing Transmission of Infections Chronic HBV infection can lead to substantial morbidity
Among Chronic Hemodialysis Patients includes testing and mortality but is detectable before the development of
recommendations for patients on hemodialysis (104). severe liver disease using reliable and inexpensive screening
tests. Routine monitoring and treatment for chronic HBV
Persons with Elevated ALT or Aspartate infection can reduce morbidity and mortality, supporting the
Aminotransferase Levels of Unknown Origin importance of early detection of HBV infection. In addition,
Persons with known chronic liver disease (e.g., cirrhosis, although not quantifiable, management of chronic infection
fatty liver disease, alcoholic liver disease, or autoimmune through prevention efforts can prevent further transmission
hepatitis) are not at increased risk for HBV infection unless to others. These recommendations consider a simpler and less
they have additional exposures or risk factors. However, persons stigmatizing implementation strategy than previous risk-based
with persistently elevated ALT or aspartate aminotransferase HBV screening recommendations. The recommendations also
(AST) levels without a known cause should be tested for HBV provide guidance that is complementary to the 2022 ACIP
infection as part of a medical evaluation of these abnormal recommendations to vaccinate all adults aged 19–59 years
laboratory values. against HBV infection (59) by providing a means to establish
immunity or any history of infection or the need for

US Department of Health and Human Services/Centers for Disease Control and Prevention MMWR / March 10, 2023 / Vol. 72 / No. 1 13
Recommendations and Reports

vaccination to protect from future infection. Specific rationales at increased risk for exposure to HBV. “Testing” refers to
for recommendations are as follows: conducting serologic testing of persons with symptoms or who
• Universal screening: Universal screening of adults is cost- are identified to be at increased risk for exposure to HBV. The
effective compared with risk-based screening and averts following evidence-based recommendations for HBV screening
liver disease and death (56). Although a curative treatment update and expand those issued by CDC in 2008 (14).
is not yet available, early diagnosis and treatment of Screening is recommended for the following persons (Box 1):
chronic HBV infections reduces the risk for cirrhosis, liver • All adults aged ≥18 years at least once during a lifetime
cancer, and death (10,11). Risk-based testing alone has (new recommendation).
not identified most persons living with chronic HBV • All pregnant persons* during each pregnancy, preferably
infection and is considered inefficient for in the first trimester, regardless of vaccination status or
providers to implement. history of testing (15) (see Clinical Considerations).
• Triple panel screening: Using the triple panel (HBsAg, Testing is recommended for the following persons (Box 1):
anti-HBs, and total anti-HBc) is recommended for initial • Everyone with a history of risk for HBV infection,
screening because it can help identify persons who have regardless of age, if they might have been susceptible
an active HBV infection and could be linked to care, have during the period of risk (Box 4) (Figure 2). Susceptible
resolved infection and might be susceptible to reactivation persons include those who have never been infected with
(e.g., immunosuppressed persons), are susceptible and HBV (i.e., total anti-HBc negative) and either did not
need vaccination, or are vaccinated. When someone complete a HepB vaccine series per ACIP recommendations
receives triple panel screening, any future periodic testing or who are known vaccine nonresponders (15).
can use tests as appropriate (e.g., only HBsAg and anti- • Susceptible persons, regardless of age, with ongoing risk
HBc if the patient is unvaccinated). should be tested periodically, while risk persists (Figure 2)
• Adults aged ≥18 years: An “all adults” recommendation (see Clinical Considerations).
was considered more feasible to implement (e.g., for ű Offer testing if the risk for exposure occurred after

integrating into electronic medical record alerts) than one previous HBV serologic testing and while the person
among specific age groups. Considerations included the was susceptible.
favorable economic analysis across adult age groups, • Anyone who requests HBV testing. These persons should
similarly low vaccination rates among adult age groups, receive testing, regardless of disclosure of risk, because
comparable epidemiology of acute and chronic infections many persons might be reluctant to disclose stigmatizing
from surveillance data among age groups, and harms of risks (new recommendation).
missed identification of chronic infections. • Persons who have an increased risk for acquiring HBV
• Children and adolescents aged <18 years: Children and infection, including the following:
adolescents aged <18 years were not included in the ű Infants born to HBsAg-positive pregnant persons (15)

universal screening recommendation because of the low ű Persons born in regions with HBV infection prevalence

prevalence of HBV infection in this age group and high of ≥2% (Box 3)
levels of HepB vaccination. Children and adolescents aged ű U.S.-born persons not vaccinated as infants whose

<18 years who have risk factors and did not receive a parents were born in regions with HBV infection
complete vaccine series should be tested (Figure 2). prevalence of ≥8% (Box 3)
• New risk groups: The addition of three new risk groups ű Persons who are injecting drug users or have a history

was based on the HBV infection prevalence cutoff of ≥1%. of IDU


The selection of the three groups for which to conduct ű Persons incarcerated or formerly incarcerated in a jail,

systematic reviews was based on expert judgment, and the prison, or other detention setting (new recommendation)
work group recognizes other populations might also be at ű Persons with HIV infection

increased risk. ű Persons with HCV infection or a past HCV infection

(new recommendation)
ű Men who have sex with men

HBV Screening and Testing


Recommendations * Pregnant person refers to anyone who can give birth, regardless of gender,
because these recommendations are inclusive of persons of any gender
In these guidelines, “screening” refers to conducting (https://uspreventiveser vicestaskforce.org/uspstf/about-uspstf/
serologic testing of asymptomatic persons not known to be methods-and-processes).

14 MMWR / March 10, 2023 / Vol. 72 / No. 1 US Department of Health and Human Services/Centers for Disease Control and Prevention
Recommendations and Reports

FIGURE 2. Incorporating hepatitis B virus screening and testing into a clinic workflow, by age
A. Nonpregnant adults aged ≥18 years without a known history of HBV infection

No/Unknown Offer screening


and vaccine

Previously Had an activity,


No/Unknown screened No Offer
exposure, or
for HBV Yes vaccine
condition associated
infection? with increased risk
since the last
screening?
Yes Offer testing
and vaccine
Completed
HepB
vaccine
series? No/Unknown Offer
screening

No No
Yes Previously Had an activity, action
screened exposure, or
for HBV Yes condition
infection? associated with
increased risk Offer testing, if the exposure
since the last Yes occurred before vaccination
screening? (while susceptible) and after
the previous HBV test(s)

B. Children and adolescents aged 1–17 years without a known history of HBV infection

No Offer vaccine,
if susceptible
Has/had an
activity,
exposure, or
No/Unknown condition
Completed associated Offer testing,
HepB with increased if the exposure occurred
vaccine Yes while susceptible
risk since the
series last screening?
as an Offer vaccine,
infant? if susceptible

Yes No
action

Per ACIP guidelines, providers should only accept dated records as evidence of HepB vaccination. Previous screening for HBV infection should include
HBsAg, anti-HBc, and anti-HBs. After the collection of blood for serologic testing, persons who have not completed a vaccine series should be offered
vaccination per ACIP guidelines at the same visit. Susceptible persons have never been infected with HBV (i.e., total anti-HBc negative) and did not
complete a HepB vaccine series per ACIP recommendations.

Abbreviations: ACIP = Advisory Committee on Immunization Practices; anti-HBc = antibody to hepatitis B core antigen; anti-HBs = antibody to hepatitis B surface
antigen; HBV = hepatitis B virus; HBsAg = hepatitis B surface antigen; HepB = hepatitis B.

US Department of Health and Human Services/Centers for Disease Control and Prevention MMWR / March 10, 2023 / Vol. 72 / No. 1 15
Recommendations and Reports

ű Persons with STIs or past STIs or multiple sex partners in this report to include a total anti-HBc test during universal
(new recommendation) (see Clinical Considerations) adult screening will support identification of persons with
ű Household contacts or former household contacts of past HBV infection who should be aware of their risk for
persons with known HBV infection reactivation in the context of immunosuppression.
ű Needle-sharing or sexual contacts of persons with known

HBV infection Clinical Considerations


ű Persons on maintenance dialysis, including in-center or
Frequency of periodic testing should be a shared decision
home hemodialysis and peritoneal dialysis (104)
ű Persons with elevated ALT or AST levels of unknown origin
between the patient and provider and based on individual
risk factors, including age and immune status. For periodic
Providers should follow these recommendations when
testing, providers should consider using the triple panel test or
offering screening and testing:
AASLD’s testing strategies (e.g., anti-HBc followed by HBsAg
• During the initial screening, test for HBsAg, anti-HBs,
and anti-HBs, if positive).
and total anti-HBc (new recommendation).
ű Screening with the three tests (triple panel) can help
Having multiple sex partners can increase the risk for
exposure to HBV and other STIs; however, evidence is
identify persons who have an active HBV infection and
insufficient to specify the number of sex partners and the
could be linked to care, have resolved infection and might
optimal time frame for screening to identify cases of chronic
be susceptible to reactivation (e.g., immunosuppressed
infection. Thus, clinical judgment should be used to determine
persons), are susceptible and need vaccination, or are
risk for exposure with consideration of the number of partners,
vaccinated (Table 1). Anti-HBs of ≥10 mIU/mL is a
type of sex, frequency of sex, and timing of the last serologic
known correlate of protection only when testing follows
test when recommending testing for persons with multiple
a complete HepB vaccine series.
sex partners.
• After the collection of blood for serologic testing, persons
In the interest of completing adult HBV screening, prenatal
who have not completed a vaccine series should be offered
visits are an opportunity to offer the triple panel to a pregnant
vaccination per ACIP recommendations at the same visit
person and link the patient to care or vaccinate as needed.
or at an associated provider visit (105). Blood collection
Pregnant persons with a history of appropriately timed triple
before vaccination is recommended because transient
panel screening and without subsequent risk for exposure to
HBsAg positivity has been reported for up to 18 days
HBV (i.e., no new HBV exposures since triple panel screening)
after vaccination.
ű Providers do not need to wait for the serologic testing
only need HBsAg screening. Testing pregnant persons known
to be chronically infected or immune enables documentation
results to administer the first or next dose of vaccine.
ű Although screening can identify persons who are
of the HBsAg test result during that pregnancy to ensure timely
prophylaxis for exposed infants.
unvaccinated and susceptible to HBV infection,
Universal screening complements a robust HepB vaccination
screening should not be a barrier to HepB vaccination,
program. Documentation of HepB vaccine administration in
especially in populations that have decreased engagement
the medical record provides verification of vaccination. Per
with or access to health care (59). In settings where
ACIP recommendations, providers should only accept dated
testing is not feasible or is refused by the patient,
records as evidence of HepB vaccination (15). For persons
vaccination of persons should continue according to
who are unvaccinated or partially vaccinated (e.g., did not
ACIP recommendations. Serologic testing should
complete a full series), HepB vaccine should be administered
continue to be offered at future visits.
immediately after collection of the blood for serologic testing.
Additional screening might be recommended for certain
Persons with evidence of active HBV infection (i.e., HBsAg
populations, including blood donors, newly arrived refugees,
positive) or a past HBV infection (i.e., total anti-HBc positive)
and persons initiating cytotoxic or immunosuppressive therapy,
do not need additional vaccine doses (15).
and additional testing might be recommended for patients on
hemodialysis, health care personnel, perinatally exposed infants,
and persons involved in exposure events that might warrant Follow-Up After HBV Testing
postexposure prophylaxis and postvaccination serologic testing.
Persons with Active HBV Infection
Recommendations for these groups are described elsewhere
(14,15,104,106–110). The new recommendation described Patients with acute infection should be counseled about
their risk for developing chronic HBV infection, the risk for
reactivation, and the risk for transmission to others. Treatment

16 MMWR / March 10, 2023 / Vol. 72 / No. 1 US Department of Health and Human Services/Centers for Disease Control and Prevention
Recommendations and Reports

BOX 4. Persons and activities, exposures, or conditions associated for acute HBV infection is not typically indicated except among
with an increased risk for hepatitis B virus infection — CDC testing patients with severe disease (11).
recommendations, 2023
Persons who receive a diagnosis of chronic HBV infection
• Infants born to pregnant persons who are hepatitis B can benefit from monitoring and counseling, including
surface antigen positive mental health support (111). CDC treatment guidelines
• Persons born in regions with hepatitis B virus (HBV) have not been developed and are beyond the scope of these
infection prevalence of ≥2% screening guidelines. However, AASLD has guidance for the
• U.S.-born persons not vaccinated as infants whose monitoring and treatment of chronic HBV infection (11).
parents were born in regions with HBV infection Simplified guidance for primary care medical providers or
prevalence of ≥8% other nonspecialists is available from the Hepatitis B Primary
• Injection drug use Care Workgroup (Table 2) (112).
• Incarceration in a jail, prison, or other detention All patients who test positive for active HBV infection should
setting (new recommendation) be provided information on how to prevent transmission to
• HIV infection others (Box 5). Notification, testing, and vaccination of their
• Hepatitis C virus infection (new recommendation) household contacts or former household contacts, sex partners,
• Men who have sex with men and needle-sharing contacts are recommended, as appropriate.
• Sexually transmitted infections or multiple sex As resources allow, viral hepatitis or STI programs within local
partners (new recommendation) or state health departments might be available to support
• Household contacts of persons with known providers with contact tracing and notification.
HBV infection Persons living with HBV infection have rights protected
• Needle-sharing or sexual contacts of persons with under the Americans with Disabilities Act (113). Persons
known HBV infection should not be excluded from practicing in the health care field
• Maintenance dialysis, including in-center or home or from school, play, child care, work, or other settings because
hemodialysis and peritoneal dialysis of their HBV infection (114,115).
• Elevated alanine aminotransferase or aspartate
Persons with Resolved (Past) HBV Infection
aminotransferase levels of unknown origin
• Persons who request HBV testing Patients should be counseled about their history of HBV
(new recommendation) infection and risk for reactivation. Therapies with the highest

TABLE 2. Initial medical evaluation of persons who are hepatitis B surface antigen positive
History/Examination Patient education Routine laboratory tests Serology/Virology Imaging/Staging studies
• Symptoms/signs of cirrhosis • Educate patients on how to • CBC • HBeAg/anti-HBe • Abdominal ultrasound with or
• Alcohol screening and prevent transmission to others • Comprehensive metabolic panel, • HBV DNA without AFP§
brief intervention • Identify household contacts, including AST/ALT, total bilirubin, • Anti-HAV (total or IgG) to • Elastography (e.g., FibroScan)
• Metabolic risk factors sex partners, or needle-sharing alkaline phosphatase, albumin, determine need for or serum fibrosis assessment
• Family history of contacts for screening and creatinine, and INR vaccination if none (e.g., APRI, FibroSure, FIB-4)
hepatocellular carcinoma vaccination documented
• Hepatitis A vaccination status; • Recommend abstinence or • Anti-HCV
offer vaccine if unvaccinated limited use of alcohol* • Anti-HDV†
• Recommend steps to reduce risk • Anti-HIV
for metabolic syndrome and • Other STIs (as indicated)
fatty liver
• Refer to harm reduction
counseling or drug treatment
services, as needed
Source: Table adapted from Tang AS, Thornton K; Hepatitis B Primary Care Workgroup. Hepatitis B management: guidance for the primary care provider. Seattle, WA:
University of Washington National Hepatitis Training Center; 2020.
Abbreviations: AFP = alpha fetoprotein; anti-HAV = antibody to hepatitis A virus; anti-HBe = antibody to hepatitis B e antigen; anti-HCV = antibody to hepatitis C virus;
anti-HDV = antibody to hepatitis D virus; APRI = AST to platelet ratio index; AST/ALT = aspartate aminotransferase/alanine aminotransferase; CBC = complete blood
count; HBeAg = hepatitis B e antigen; HBsAg = hepatitis B surface antigen; HBV = hepatitis B virus; INR = international normalized ratio; STI = sexually transmitted infection.
* More than seven alcoholic drinks/week for women and more than 14 drinks/week for men is associated with increased risk for liver disease (Source: Terrault NA, Lok
ASF, McMahon BJ, et al. Update on prevention, diagnosis, and treatment of chronic hepatitis B: AASLD 2018 hepatitis B guidance. Hepatology 2018;67:1560–99).
† Source: AASLD Practice Guidelines (https://www.aasld.org/practice-guidelines).
§ Ultrasound for hepatocellular carcinoma surveillance has higher diagnostic accuracy than AFP; therefore, AFP alone is not recommended except when ultrasound
is unavailable or unaffordable (Source: Terrault NA, Lok ASF, McMahon BJ, et al. Update on prevention, diagnosis, and treatment of chronic hepatitis B: AASLD 2018
hepatitis B guidance. Hepatology 2018;67:1560–99).

US Department of Health and Human Services/Centers for Disease Control and Prevention MMWR / March 10, 2023 / Vol. 72 / No. 1 17
Recommendations and Reports

BOX 5. Prevention messages for persons with hepatitis B virus infection

• To prevent or reduce risk for transmission to others, persons who are hepatitis B surface antigen (HBsAg) positive should
take the following actions:
ű Notify their household, sexual, and needle-sharing contacts that they should be tested for markers of hepatitis B virus

(HBV) infection; if susceptible, contacts should complete the hepatitis B (HepB) vaccine series
ű Use condoms to protect susceptible sex partners from acquiring HBV infection from sexual activity until the sex

partners can be vaccinated and their immunity documented (condoms and other prevention methods can also reduce
risks for other sexually transmitted infections
ű Cover cuts and skin lesions to prevent spread of infectious secretions or blood
ű Clean blood spills with bleach solution*
ű Refrain from donating blood, plasma, tissue, or semen
ű Refrain from sharing household articles (e.g., toothbrushes and razors) that could become contaminated with blood
ű Refrain from sharing needles, syringes, and other injection equipment
ű Dispose of blood, body fluids, and medical waste properly

• Newborns of pregnant persons who are HBsAg positive should receive the HepB vaccine and HepB immune globulin at
birth and complete the HepB vaccine series according to the recommended vaccination schedule.†
• When seeking medical or dental care, persons who are HBsAg positive should tell those responsible for their care of their
HBsAg status so they can be evaluated and managed appropriately.
* Source: Rutala WA, Weber DJ; Healthcare Infection Control Practices Advisory Committee. Guideline for disinfection and sterilization in healthcare facilities,
2008. Atlanta, GA: US Department of Health and Human Services, CDC; 2008. https://stacks.cdc.gov/view/cdc/47378
† Source: Schillie S, Vellozzi C, Reingold A, et al. Prevention of hepatitis B virus infection in the United States: recommendations of the Advisory Committee on
Immunization Practices. MMWR Recomm Rep 2018;67:(No. RR-1):1–31.

risk for reactivation include B-cell depleting agents (e.g., persons who have initiated, but not completed, the HepB
rituximab and ofatumumab). American Society of Clinical vaccine series, regardless of anti-HBs status. HepB vaccine
Oncology and AASLD guidelines have more information series completion is important for long-term immunogenicity.
on therapies and conditions associated with increased risk Persons who are susceptible, refuse vaccination, and are at
for reactivation, as well as recommendations for treatment increased risk for HBV infection should be periodically tested.
(11,109,116,117). Antiviral therapy for HBV infection, when Frequency of periodic testing should be a shared decision
initiated before immunosuppressive or cytotoxic therapy, between the patient and provider and be based on individual
can prevent reactivation of disease (118). The systematic risk factors and immune status.
review indicated the prevalence of resolved HBV infection
(i.e., HBsAg negative and anti-HBc positive) in the general Persons Who Are Fully Vaccinated
population ranges from 4.8% to 14.0% (median = 6.2%). Against HBV Infection
Notification, testing, and vaccination of household, sex partners, Persons are considered fully vaccinated if they have
and needle-sharing contacts of patients with HBV infection or completed a HepB vaccine series and can be reassured about
a history of HBV infection are recommended, as appropriate. protection against future illness. Vaccination status should
be clearly documented in the medical record. Anti-HBs
Persons Who Are Susceptible to HBV Infection concentrations can wane over time among vaccine responders
Persons who are susceptible to HBV infection should be (20). For persons with a clearly documented vaccination series
told that they have never been infected with HBV and are who test negative for anti-HBs, refer to Prevention of Hepatitis B
not protected from future infection. All persons who are Virus Infection in the United States: Recommendations of the
susceptible to infection should be offered HepB vaccine per Advisory Committee on Immunization Practices for specific
ACIP recommendations (59). Anti-HBs concentrations can populations for whom revaccination might be recommended
wane over time among vaccine responders. For persons with (e.g., patients on hemodialysis) (15). Revaccination or booster
a clearly documented vaccination series who test negative for doses are not routinely recommended for persons who are
anti-HBs, refer to Prevention of Hepatitis B Virus Infection in immunocompetent (15).
the United States: Recommendations of the Advisory Committee
on Immunization Practices (15). Vaccine should be offered to

18 MMWR / March 10, 2023 / Vol. 72 / No. 1 US Department of Health and Human Services/Centers for Disease Control and Prevention
Recommendations and Reports

Persons with Isolated Core Antibody Recommendations and Guidance


Persons with isolated anti-HBc should have their immune from Non-CDC Sources
status and risk history considered before deciding next steps.
Links to performance characteristics on all FDA-approved USPSTF, AASLD, and ACP also have published HBV
total anti-HBc assays are available (Supplementary Table 21, screening recommendations. The 2021 USPSTF systematic
https://stacks.cdc.gov/view/cdc/124432). The specificity of review found that no study directly evaluated the effects of
total anti-HBc tests is 99.8% (119,120). However, if a person screening for HBV infection on clinical outcomes and that
does not have risk factors, the result might be a false positive; risk-based screening strategies identify nearly all patients
repeat testing with the same assay is warranted to confirm the with HBV infection (126). USPSTF recommends screening
results (121). A false-positive isolated core antibody result adolescents and adults at increased risk for HBV infection with
means the person is susceptible and should be offered HepB HBsAg tests. Although the work group did not identify any
vaccine per current ACIP recommendations (105). studies directly comparing the effects of universal screening
A 2001–2018 national survey found the prevalence of versus risk-based screening, the cost-effectiveness analysis,
isolated positive anti-HBc to be 0.8% (approximately indirect evidence on the effects of screening, practicality of
2.1 million persons) (122). Among patients exposed to HBV, implementing guidelines, public health benefits, and subject
an isolated positive anti-HBc result might be the result of matter expertise were considered. The work group concluded
loss of anti-HBs after past resolved infection, occult infection that the benefits of universal screening outweighed the costs.
(i.e., HBsAg is negative, but HBV DNA is positive), being AASLD also recommends screening persons at increased
in the window period before appearance of anti-HBs, or an risk for infection; however, this guidance primarily is based
HBsAg mutant infection (i.e., an infection that is not picked on previous CDC recommendations. AASLD guidance
up by an HBsAg test unable to detect mutants). Patients who differs from CDC guidance by recommending screening
are immunosuppressed should be considered at risk for HBV of unvaccinated persons with diabetes aged 19–49 years,
reactivation, and HBV DNA testing is recommended to assess travelers to countries with intermediate or high prevalence
for occult infection (11). Among infants, an isolated anti-HBc of HBV infection, and residents and staff of facilities for
result might be a consequence of passive placental transfer from developmentally disabled persons (11). CDC recommends
an HBsAg-positive mother, which is why testing for anti-HBc universal adult screening, but not periodic testing, for these
is not indicated before age 24 months (15). groups. AASLD also only recommends anti-HBc testing for
certain groups (11).
In their best practice advice, ACP and CDC recommend
Patient Education testing persons at increased risk for HBV infection with
Patient education should be conducted in a culturally tests for HBsAg, total anti-HBc, and anti-HBs (121). The
sensitive, nonstigmatizing manner in the patient’s primary ACP best practice risk groups align with current testing
language (both written and oral whenever possible). Bilingual, recommendations except that ACP omits persons with a history
bicultural, and medically trained interpreters should be used of STIs or multiple sex partners (Box 4).
when indicated. CDC screening guidelines were developed independently
from the ACIP recommendations for HepB vaccination. The
Reporting 2018 ACIP recommendations also include recommendations
for serologic testing (15). CDC’s screening and testing
Acute and chronic cases of HBV infection should be guidelines cover all persons recommended for serologic
reported to the appropriate state or local health jurisdiction testing per ACIP and expand beyond that list (Box 1).
in accordance with requirements. The Council of State and When considering prevaccination testing or testing for HBV
Territorial Epidemiologists publishes case definitions for the infection, CDC recommends testing that follows a universal
classification of reportable cases of HBV infection (123,124). testing approach (Figure 2).
CDC has updated guidance for health departments on viral The work group did not evaluate clinical guidance for patients
hepatitis surveillance and case management (125). after screening. The most recent expert guidance to reduce the
risk for liver damage is that patients with HBV infection should
be vaccinated against hepatitis A virus (if not already immune)
(112); screened for HIV, HCV, and hepatitis D virus (HDV)
(112); and assessed for alcohol risk factors, such as with the

US Department of Health and Human Services/Centers for Disease Control and Prevention MMWR / March 10, 2023 / Vol. 72 / No. 1 19
Recommendations and Reports

alcohol screening and brief intervention (127). Depending on Acknowledgments


the likely route of transmission, the patient might benefit from Saleem Kamili, Susan Ingber, Olivia Russell, Greta Tessman,
STI screening, drug treatment, or harm-reduction counseling. National Center for HIV, Viral Hepatitis, STD, and TB Prevention,
A full list of recommended steps for examination, education, Division of Viral Hepatitis, CDC.
laboratory, serology, and imaging is provided (Table 2).
Additional screening might be recommended for blood Contributors
donors, newly arrived refugees, and persons initiating Karina Rapposelli, Division of Viral Hepatitis, National Center for HIV,
Viral Hepatitis, STD, and TB Prevention, CDC; Amy L. Sandul, Division
cytotoxic or immunosuppressive and additional testing of Viral Hepatitis, National Center for HIV, Viral Hepatitis, STD, and
might be recommended for patients on hemodialysis, TB Prevention, CDC; Elisa Choi, Harvard Vanguard Medical Associates
health care personnel, perinatally exposed infants, and Somerville and American College of Physicians; Carla Coffin, Calvin,
persons involved in exposure events who might warrant Phoebe and Joan Snyder Institute for Chronic Diseases, Cumming School of
Medicine, University of Calgary and Calgary Liver Unit, Calgary Division of
postexposure prophylaxis and postvaccination serologic Gastroenterology and Hepatology, Alberta Health Services; Kristen Marks,
testing. These recommendations are described elsewhere Division of Infectious Disease, Weill Cornell Medical College; David L.
(14,15,104,106–110). Providers should follow the most Thomas, Johns Hopkins School of Medicine and Bloomberg School of
Public Health; Su H. Wang, Cooperman Barnabas Medical Center and
conservative approach when recommendations differ. RWJ Barnabas-Rutgers Medical Group.

Conflicts of Interest
Future Directions All authors have completed and submitted the International
CDC will review these recommendations as new treatments, Committee of Medical Journal Editors form for disclosure of
tests, epidemiology, HepB vaccination rates, and experience potential conflicts of interest. No potential conflicts of interest
gained from implementation of these recommendations become were reported.
available; recommendations will be revised as needed. The work References
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jama.2020.22980

US Department of Health and Human Services/Centers for Disease Control and Prevention MMWR / March 10, 2023 / Vol. 72 / No. 1 25
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