CDC Recommendations - U.S. 2023:Screening and Testing for Hepatitis B Virus Infection

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.

Interpretation of Screening Tests

The three main serologic markers used to determine HBV infection status are hepatitis B surface antigen (HBsAg), antibody to hepatitis B surface antigen (anti-HBs), and antibody to hepatitis B core antigen (anti-HBc). Serologic markers change over typical courses of resolved acute infection and progression to chronic infection.

Persons with an Increased Risk for HBV Infection Recommended for Testing

• Persons with HCV Infection or a Past HCV Infection

• Persons Incarcerated or Formerly Incarcerated in a Jail, Prison, or Other Detention Setting

• Persons with Sexually Transmitted Infections or a History of Sexually Transmitted Infections or Multiple Sex Partners

• Infants Born to Pregnant Persons Who Are HBsAg Positive

• Persons Born in Regions with HBV Infection Prevalence of ≥2%

• Persons Born in the United States Not Vaccinated as Infants Whose Parents Were Born in Regions with HBV Infection Prevalence of ≥8%

• Persons Who Use Injection Drugs or Have a History of IDU

• Persons with HIV Infection

• MSM

• Household, Needle-Sharing, or Sexual Contacts of Persons with Known HBV Infection

• Persons on Dialysis, Hemodialysis, or Peritoneal Dialysis

• Persons with Elevated ALT or Aspartate Aminotransferase Levels of Unknown Origin
  

Rationale for New Recommendations

Chronic HBV infection can lead to substantial morbidity and mortality but is detectable before the development of severe liver disease using reliable and inexpensive screening tests. Routine monitoring and treatment for chronic HBV infection can reduce morbidity and mortality, supporting the importance of early detection of HBV infection. In addition, although not quantifiable, management of chronic infection through prevention efforts can prevent further transmission to others. These recommendations consider a simpler and less stigmatizing implementation strategy than previous risk-based HBV screening recommendations. The recommendations also provide guidance that is complementary to the 2022 ACIP recommendations to vaccinate all adults aged 19–59 years against HBV infection by providing a means to establish immunity or any history of infection or the need for vaccination to protect from future infection. Specific rationales for recommendations are as follows:

• Universal screening: Universal screening of adults is cost-effective compared with risk-based screening and averts liver disease and death. Although a curative treatment is not yet available, early diagnosis and treatment of chronic HBV infections reduces the risk for cirrhosis, liver cancer, and death. Risk-based testing alone has not identified most persons living with chronic HBV infection and is considered inefficient for providers to implement.

• Triple panel screening: Using the triple panel (HBsAg, anti-HBs, and total anti-HBc) is recommended for initial screening because it 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. When someone receives triple panel screening, any future periodic testing can use tests as appropriate (e.g., only HBsAg and anti-HBc if the patient is unvaccinated).

• Adults aged ≥18 years: An “all adults” recommendation was considered more feasible to implement (e.g., for integrating into electronic medical record alerts) than one among specific age groups. Considerations included the favorable economic analysis across adult age groups, similarly low vaccination rates among adult age groups, comparable epidemiology of acute and chronic infections from surveillance data among age groups, and harms of missed identification of chronic infections.

• Children and adolescents aged <18 years: Children and adolescents aged <18 years were not included in the universal screening recommendation because of the low prevalence of HBV infection in this age group and high levels of HepB vaccination. Children and adolescents aged <18 years who have risk factors and did not receive a complete vaccine series should be tested (Figure 1).

• New risk groups: The addition of three new risk groups was based on the HBV infection prevalence cutoff of ≥1%. The selection of the three groups for which to conduct systematic reviews was based on expert judgment, and the work group recognizes other populations might also be at increased risk.
  

FIGURE 1. Incorporating hepatitis B virus screening and testing into a clinic workflow, by age

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.

Screening is recommended for the following persons:

• 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.
  

Testing is recommended for the following persons:

• Everyone with a history of risk for HBV infection, regardless of age, if they might have been susceptible during the period of risk (Figure 1). 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.

• Susceptible persons, regardless of age, with ongoing risk should be tested periodically, while risk persists (Figure 1).

  • 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

  • Persons born in regions with 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%

  • 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)

  • 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

  • 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. 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. 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. 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. 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.

Follow-Up After HBV Testing

Persons with Active HBV Infection

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 for acute HBV infection is not typically indicated except among patients with severe disease.

Persons who receive a diagnosis of chronic HBV infection can benefit from monitoring and counseling, including mental health support. CDC treatment guidelines have not been developed and are beyond the scope of these screening guidelines. However, AASLD has guidance for the monitoring and treatment of chronic HBV infection. Simplified guidance for primary care medical providers or other nonspecialists is available from the Hepatitis B Primary Care Workgroup (Table 1).

TABLE 1. Initial medical evaluation of persons who are hepatitis B surface antigen positive

All patients who test positive for active HBV infection should be provided information on how to prevent transmission to others. Notification, testing, and vaccination of their household contacts or former household contacts, sex partners, and needle-sharing contacts are recommended, as appropriate. As resources allow, viral hepatitis or STI programs within local or state health departments might be available to support providers with contact tracing and notification.

Persons living with HBV infection have rights protected under the Americans with Disabilities Act. Persons should not be excluded from practicing in the healthcare field or from school, play, child care, work, or other settings because of their HBV infection.

Persons with Resolved (Past) HBV Infection

Patients should be counseled about their history of HBV infection and risk for reactivation. Therapies with the highest risk for reactivation include B-cell depleting agents (e.g., rituximab and ofatumumab). American Society of Clinical Oncology and AASLD guidelines have more information on therapies and conditions associated with increased risk for reactivation, as well as recommendations for treatment. Antiviral therapy for HBV infection, when initiated before immunosuppressive or cytotoxic therapy, can prevent reactivation of disease. The systematic review indicated the prevalence of resolved HBV infection (i.e., HBsAg negative and anti-HBc positive) in the general population ranges from 4.8% to 14.0% (median = 6.2%). Notification, testing, and vaccination of household, sex partners, and needle-sharing contacts of patients with HBV infection or a history of HBV infection are recommended, as appropriate.

Persons Who Are Susceptible to HBV Infection

Persons who are susceptible to HBV infection should be told that they have never been infected with HBV and are not protected from future infection. All persons who are susceptible to infection should be offered HepB vaccine per ACIP recommendations. Anti-HBs concentrations can wane over time among vaccine responders. For persons with a clearly documented vaccination series who test negative for anti-HBs, refer to Prevention of Hepatitis B Virus Infection in the United States: Recommendations of the Advisory Committee on Immunization Practices. Vaccine should be offered to persons who have initiated, but not completed, the HepB vaccine series, regardless of anti-HBs status. HepB vaccine series completion is important for long-term immunogenicity.

Persons who are susceptible, refuse vaccination, and are at increased risk for HBV infection should be periodically tested. Frequency of periodic testing should be a shared decision between the patient and provider and be based on individual risk factors and immune status.

Persons Who Are Fully Vaccinated Against HBV Infection

Persons are considered fully vaccinated if they have completed a HepB vaccine series and can be reassured about protection against future illness. Vaccination status should be clearly documented in the medical record. Anti-HBs concentrations can wane over time among vaccine responders. For persons with a clearly documented vaccination series who test negative for anti-HBs, refer to Prevention of Hepatitis B Virus Infection in the United States: Recommendations of the Advisory Committee on Immunization Practices for specific populations for whom revaccination might be recommended (e.g., patients on hemodialysis). Revaccination or booster doses are not routinely recommended for persons who are immunocompetent.

Persons with Isolated Core Antibody

Persons with isolated anti-HBc should have their immune status and risk history considered before deciding next steps. Links to performance characteristics on all FDA-approved total anti-HBc assays are available. The specificity of total anti-HBc tests is 99.8%. However, if a person does not have risk factors, the result might be a false positive; repeat testing with the same assay is warranted to confirm the results. A false-positive isolated core antibody result means the person is susceptible and should be offered HepB vaccine per current ACIP recommendations.

A 2001–2018 national survey found the prevalence of isolated positive anti-HBc to be 0.8% (approximately 2.1 million persons). Among patients exposed to HBV, an isolated positive anti-HBc result might be the result of loss of anti-HBs after past resolved infection, occult infection (i.e., HBsAg is negative, but HBV DNA is positive), being in the window period before appearance of anti-HBs, or an HBsAg mutant infection (i.e., an infection that is not picked up by an HBsAg test unable to detect mutants). Patients who are immunosuppressed should be considered at risk for HBV reactivation, and HBV DNA testing is recommended to assess for occult infection. Among infants, an isolated anti-HBc result might be a consequence of passive placental transfer from an HBsAg-positive mother, which is why testing for anti-HBc is not indicated before age 24 months.

Patient Education

Patient education should be conducted in a culturally sensitive, nonstigmatizing manner in the patient’s primary language (both written and oral whenever possible). Bilingual, bicultural, and medically trained interpreters should be used when indicated.

Reporting

Acute and chronic cases of HBV infection should be reported to the appropriate state or local health jurisdiction in accordance with requirements. The Council of State and Territorial Epidemiologists publishes case definitions for the classification of reportable cases of HBV infection. CDC has updated guidance for health departments on viral hepatitis surveillance and case management.

Future Directions

CDC will review these recommendations as new treatments, tests, epidemiology, HepB vaccination rates, and experience gained from implementation of these recommendations become available; recommendations will be revised as needed. The work group did not conduct a systematic review to reassess any of the groups at increased risk for HBV infection from the 2008 guidelines; future recommendations might modify the groups recommended for periodic testing. Additional data on the ideal frequency of periodic testing is needed. Continued collaboration with laboratories to bundle the three HBV tests (HBsAg, anti-HBs, and anti-HBc) would facilitate ordering the tests together as a triple panel. In addition, reporting a triple panel summary result will aid providers in correctly interpreting results. Finally, a better understanding of the prevalence of HDV in the United States is needed to inform recommendations for HDV screening among persons with HBV infection.

Conclusion

Universal screening of adults for HBV infection is cost-effective compared with risk-based screening and averts liver disease and death. Although a curative treatment is not yet available, early diagnosis and treatment of chronic HBV infections reduces the risk for cirrhosis, liver cancer, and death. Risk-based testing alone has not identified most persons living with chronic HBV infection and is inefficient for providers to implement. Along with vaccination strategies, universal screening of adults and appropriate testing of persons at increased risk for HBV infection will improve health outcomes, reduce the prevalence of HBV infection in the United States, and advance viral hepatitis elimination goals.

August 1, 2023

CENTERS FOR DIAEASE CONTROL AND PREVENTION

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