Screening and Testing for Hepatitis B Virus Infection

Publication Date: March 9, 2023
Last Updated: March 10, 2023

HBV Screening and Testing Recommendations

In these guidelines, “screening” refers to conducting serologic testing of asymptomatic persons not known to be at increased risk for exposure to HBV. “Testing” refers to conducting serologic testing of persons with symptoms or who are identified to be at increased risk for exposure to HBV. The following evidence-based recommendations for HBV screening update and expand those issued by CDC in 2008 (14).

Screening is recommended for the following persons (Box 1):
  • All adults aged ≥18 years at least once during a lifetime (new recommendation).
  • All pregnant persons* during each pregnancy, preferably in the first trimester, regardless of vaccination status or history of testing (15) (see Clinical Considerations).

Testing is recommended for the following persons (Box 1):
  • Everyone with a history of risk for HBV infection, regardless of age, if they might have been susceptible during the period of risk (Box 4) (Figure 2). 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 ACIP recommendations or who are known vaccine nonresponders (15).
  • Susceptible persons, regardless of age, with ongoing risk should be tested periodically, while risk persists (Figure 2) (see Clinical Considerations).
  • Offer testing if the risk for exposure occurred after previous HBV serologic testing and while the person was susceptible.
  • Anyone who requests HBV testing. These persons should receive testing, regardless of disclosure of risk, because many persons might be reluctant to disclose stigmatizing risks (new recommendation).
  • Persons who have an increased risk for acquiring HBV infection, including the following:
    • Infants born to HBsAg-positive pregnant persons (15)
    • Persons born in regions with HBV infection prevalence of ≥2% (Box 3)
    • U.S.-born persons not vaccinated as infants whose parents were born in regions with HBV infection prevalence of ≥8% (Box 3)
    • Persons who are injecting drug users or have a history of IDU
    • Persons incarcerated or formerly incarcerated in a jail, prison, or other detention setting (new recommendation)
    • Persons with HIV infection
    • Persons with HCV infection or a past HCV infection (new recommendation)
    • Men who have sex with men
    • Persons with STIs or past STIs or multiple sex partners (new recommendation) (see Clinical Considerations)
    • Household contacts or former household contacts of persons with known HBV infection
    • Needle-sharing or sexual contacts of persons with known HBV infection
    • Persons on maintenance dialysis, including in-center or home hemodialysis and peritoneal dialysis (104)
    • Persons with elevated ALT or AST levels of unknown origin

Providers should follow these recommendations when offering screening and testing:
  • During the initial screening, test for HBsAg, anti-HBs, and total anti-HBc (new recommendation).
    • Screening with the three tests (triple panel) can help identify persons who have an active HBV infection and could be linked to care, have resolved infection and might be susceptible to reactivation (e.g., immunosuppressed persons), are susceptible and need vaccination, or are vaccinated (Table 1). Anti-HBs of ≥10 mIU/mL is a known correlate of protection only when testing follows a complete HepB vaccine series.
  • After the collection of blood for serologic testing, persons who have not completed a vaccine series should be offered vaccination per ACIP recommendations at the same visit or at an associated provider visit (105). Blood collection before vaccination is recommended because transient HBsAg positivity has been reported for up to 18 days after vaccination.
    • Providers do not need to wait for the serologic testing results to administer the first or next dose of vaccine.
    • Although screening can identify persons who are unvaccinated and susceptible to HBV infection, screening should not be a barrier to HepB vaccination, especially in populations that have decreased engagement with or access to health care (59). In settings where testing is not feasible or is refused by the patient, vaccination of persons should continue according to ACIP recommendations. Serologic testing should continue to be offered at future visits.

Additional screening might be recommended for certain populations, including blood donors, newly arrived refugees, and persons initiating cytotoxic or immunosuppressive therapy, 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 postexposure prophylaxis and postvaccination serologic testing. Recommendations for these groups are described elsewhere (14,15,104,106–110). The new recommendation described in this report to include a total anti-HBc test during universal adult screening will support identification of persons with past HBV infection who should be aware of their risk for reactivation in the context of immunosuppression.

Recommendations and Guidance from Non-CDC Sources

USPSTF, AASLD, and ACP also have published HBV screening recommendations.
  • The 2021 USPSTF systematic review found that no study directly evaluated the effects of screening for HBV infection on clinical outcomes and that risk-based screening strategies identify nearly all patients with HBV infection. USPSTF recommends screening adolescents and adults at increased risk for HBV infection with HBsAg tests. Although the work group did not identify any studies directly comparing the effects of universal screening versus risk-based screening, the cost-effectiveness analysis, indirect evidence on the effects of screening, practicality of implementing guidelines, public health benefits, and subject matter expertise were considered. The work group concluded that the benefits of universal screening outweighed the costs.
  • AASLD also recommends screening persons at increased risk for infection; however, this guidance primarily is based on previous CDC recommendations. AASLD guidance differs from CDC guidance by recommending screening of unvaccinated persons with diabetes aged 19–49 years, travelers to countries with intermediate or high prevalence of HBV infection, and residents and staff of facilities for developmentally disabled persons (11). CDC recommends universal adult screening, but not periodic testing, for these groups. AASLD also only recommends anti-HBc testing for certain groups (11).
  • In their best practice advice, ACP and CDC recommend testing persons at increased risk for HBV infection with tests for HBsAg, total anti-HBc, and anti-HBs (121). The ACP best practice risk groups align with current testing recommendations except that ACP omits persons with a history of STIs or multiple sex partners (Box 4).
  • CDC screening guidelines were developed independently from the ACIP recommendations for HepB vaccination. The 2018 ACIP recommendations also include recommendations for serologic testing (15). CDC’s screening and testing guidelines cover all persons recommended for serologic testing per ACIP and expand beyond that list (Box 1). When considering prevaccination testing or testing for HBV infection, CDC recommends testing that follows a universal testing approach (Figure 2).
  • The work group did not evaluate clinical guidance for patients 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 alcohol screening and brief intervention (127). Depending on the likely route of transmission, the patient might benefit from STI screening, drug treatment, or harm-reduction counseling. A full list of recommended steps for examination, education, laboratory, serology, and imaging is provided (Table 2).
  • Additional screening might be recommended for blood donors, newly arrived refugees, and persons initiating cytotoxic or immunosuppressive and additional testing might be recommended for patients on hemodialysis, health care personnel, perinatally exposed infants, and persons involved in exposure events who might warrant postexposure prophylaxis and postvaccination serologic testing. These recommendations are described elsewhere (14,15,104,106–110). Providers should follow the most conservative approach when recommendations differ.

Tablea and Lists

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.

TABLE 1. Interpretation of screening test results for hepatitis B virus infection and recommended actions

Having trouble viewing table?
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 from receipt of previous vaccination) Negative Positive¶ Negative Negative Reassure if history of HepB vaccine series completion; if partially vaccinated, complete 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
* 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.

BOX 2. Rationale for universal hepatitis B virus screening

  • Hepatitis B virus (HBV) infection has substantial morbidity and mortality.
  • Chronic HBV infection can be detected before the development of severe liver disease using reliable and inexpensive screening tests.
  • Treatment for chronic HBV infection can reduce morbidity and mortality.
  • Management of chronic HBV infection might prevent transmission to others.
  • Universal screening of adults is cost-effective.
  • Screening enables identification and management of pregnant persons infected with HBV and their infants, which can reduce the risk for perinatal transmission.
  • Screening can identify persons who are at risk for reactivation of HBV infection.
  • Screening might identify persons who would benefit from hepatitis B vaccination.

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

FIGURE 2. Incorporating hepatitis B virus screening and testing into a clinic workflow, by age

BOX 4. Persons and activities, exposures, or conditions associated with an increased risk for hepatitis B virus infection — CDC testing recommendations, 2023

  • Infants born to pregnant persons who are hepatitis B surface antigen positive
  • Persons born in regions with hepatitis B virus (HBV) infection prevalence of ≥2%
  • U.S.-born persons not vaccinated as infants whose parents were born in regions with HBV infection prevalence of ≥8%
  • Injection drug use
  • Incarceration in a jail, prison, or other detention setting (new recommendation)
  • HIV infection
  • Hepatitis C virus infection (new recommendation)
  • Men who have sex with men
  • Sexually transmitted infections or multiple sex partners (new recommendation)
  • Household contacts of persons with known HBV infection
  • Needle-sharing or sexual contacts of persons with known HBV infection
  • Maintenance dialysis, including in-center or home hemodialysis and peritoneal dialysis
  • Elevated alanine aminotransferase or aspartate aminotransferase levels of unknown origin
  • Persons who request HBV testing (new recommendation)

TABLE 2. Initial medical evaluation of persons who are hepatitis B surface antigen positive

History/Examination
• Symptoms/signs of cirrhosis
• Alcohol screening and brief intervention
• Metabolic risk factors
• Family history of hepatocellular carcinoma
• Hepatitis A vaccination status; offer vaccine if unvaccinated

Patient education
• Educate patients on how to prevent transmission to others
• Identify household contacts, sex partners, or needle-sharing contacts for screening and vaccination
• Recommend abstinence or limited use of alcohol*
• Recommend steps to reduce risk for metabolic syndrome and fatty liver
• Refer to harm reduction counseling or drug treatment services, as needed

Routine laboratory tests
• CBC
• Comprehensive metabolic panel, including AST/ALT, total bilirubin, alkaline phosphatase, albumin, creatinine, and INR

Serology/Virology
• HBeAg/anti-HBe
• HBV DNA
• Anti-HAV (total or IgG) to determine need for vaccination if none documented
• Anti-HCV
• Anti-HDV†
• Anti-HIV
• Other STIs (as indicated)

Imaging/Staging studies
• Abdominal ultrasound with or without AFP§
• Elastography (e.g., FibroScan) or serum fibrosis assessment (e.g., APRI, FibroSure, FIB-4)

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:
    • 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
    • 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
    • Cover cuts and skin lesions to prevent spread of infectious secretions or blood
    • Clean blood spills with bleach solution*
    • Refrain from donating blood, plasma, tissue, or semen
    • Refrain from sharing household articles (e.g., toothbrushes and razors) that could become contaminated with blood
    • Refrain from sharing needles, syringes, and other injection equipment
    • 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.

Recommendation Grading

Disclaimer

The information in this patient summary should not be used as a substitute for professional medical care or advice. Contact a health care provider if you have questions about your health.

Overview

Title

Screening and Testing for Hepatitis B Virus Infection

Authoring Organization

Centers for Disease Control and Prevention

Publication Month/Year

March 9, 2023

Last Updated Month/Year

April 1, 2024

Supplemental Implementation Tools

Document Type

Guideline

Country of Publication

US

Document Objectives

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.

Inclusion Criteria

Male, Female, Adult, Older adult

Health Care Settings

Ambulatory, Correctional facility, Hospital

Intended Users

Nurse, nurse practitioner, physician, physician assistant

Diseases/Conditions (MeSH)

D006510 - Hepatitis B Antibodies, D006509 - Hepatitis B, D017325 - Hepatitis B Vaccines, D006515 - Hepatitis B virus, D006511 - Hepatitis B Antigens

Keywords

screening, immunization, hepatitis B, HBV, vaccinations, vaccine

Source Citation

Conners EE, Panagiotakopoulos L, Hofmeister MG, et al. Screening and Testing for Hepatitis B Virus Infection: CDC Recommendations — United States, 2023. MMWR Recomm Rep 2023;72(No. RR-1):1–25. DOI: http://dx.doi.org/10.15585/mmwr.rr7201a1

Methodology

Number of Source Documents
127
Literature Search Start Date
December 31, 2007
Literature Search End Date
February 7, 2021