Screening and Testing for Hepatitis B Virus Infection

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.

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.