HBV Triple Screen Panel With Reflexes

HBV Triple Screen Panel With Reflexes

This test is used to screen for current or past hepatitis B virus infection and vaccination status.

See also 1 related tests 2 related guides Test Guide List

HBV Screen Panel With Reflexes

Test Summary

 

HBV Triple Screen Panel With Reflexes

Test code: 39170         

 

Clinical use

  • Screen or test for hepatitis B virus (HBV) infection and assess immune status

Clinical background

HBV is a viral pathogen that infects the liver and causes hepatitis B, an inflammatory liver disease. For unimmunized persons, symptoms of acute hepatitis can range from being asymptomatic or include fever, fatigue, loss of appetite, nausea, vomiting, abdominal pain, dark urine, and jaundice.1 In the United States, an estimated 13,000 people had new HBV infections in 2021.2 Additionally, an estimated 580,000 to 1.17 million people live with CHB,1 about two-thirds of whom do not know they have HBV infection.3 Though most people with CHB are asymptomatic, they remain infectious and have increased risk of life-threatening complications, including cirrhosis and hepatocellular carcinoma.1 Detecting acute and chronic HBV infections is important to prevent further transmission and reduce morbidity and mortality from CHB.

Screening for HBV is recommended for all adults aged 18 years and older at least once in their lifetime and all pregnant persons during each pregnancy.1 Expanded risk-based testing is recommended for people with elevated risk of infection or complications from hepatitis B, those requiring immunosuppressive therapy, and others listed in Table 1.1,3–6 Periodic screening may be appropriate for those with ongoing risk of infection.5,6 In addition to helping connect those with HBV infections to care, testing can also help identify people susceptible to HBV for whom vaccination may be appropriate.1,3,4,6

Table 1. People Suitable for HBV Testing

  • People born in moderately (prevalence ≥2%) or highly endemic areas1,6
  • Unvaccinated children of people born in highly endemic (prevalence ≥8%) areas1,5,6
  • People who have traveled to highly or moderately endemic areas3
  • Pregnant womena
  • Children born to women with HBV infection1,4
  • People who use intravenous drugs (current or past)1,3–6
  • Men who have sex with men1,3–6
  • People who have a history of sexually transmitted infections or high-risk sexual activities1,3–6
  • Household and sexual contacts of people with HBV infection1,3–6
  • Healthcare and public safety workers at risk of exposure to blood-borne pathogens1,4
  • People living or working at facilities for developmentally disabled people1,4–6
  • People who are incarcerated or in detention settings1,3–6
  • People requiring immunosuppressive therapy1,3–6
  • People with end-stage renal disease (receiving dialysis)1,3–6
  • People with hepatitis C virus (HCV) or HIV infection1,3–6
  • People with diabetes who are age 19 to 59 years, if not vaccinated1,4,6
  • Persons with elevated ALT or AST levels of unknown origin
a Testing with a hepatitis B surface antigen (HBsAg) test is recommended with follow-up testing for those with positive results.1,3,4,6

 

For screening, the Centers for Disease Control and Prevention and the American College of Physicians recommend using tests for 3 serologic markers together (ie, a “triple screen”) to help evaluate HBV infection and immune status.1,3,6 These markers include hepatitis B surface antigen (HBsAg), the antibody (HBsAb) to the surface antigen, and the total (IgG and IgM) antibody (HBcAb) to the HBV core antigen. HBsAg is a marker of HBV infection (acute and chronic) and infectiousness7; tests are >98% sensitive and specific for HBV.5 HBsAb is a marker of resolved HBV infection or response to vaccination; titers ≥10 mIU/mL indicate immunity.1,7 HBcAb is a marker of current or past infection; however, IgM is present only during the acute phase of infection.7

HBV Triple Screen Panel with Reflexes (test code 39170) includes a qualitative test for HBsAg, a quantitative test for HBsAb, and a qualitative test for HBcAb. Reflex testing is performed on specimens with positive HBsAg results (to a confirmatory test) and specimens with positive HBcAb results (to an IgM test). Reflex tests are performed at an additional charge with additional CPT codes. Individual components of this panel may be ordered separately (Hepatitis B Surface Antigen with Reflex Confirmation, test code 498; Hepatitis B Surface Antibody Immunity, Quantitative, test code 8475; Hepatitis B Core Antibody, Total, with Reflex to IgM, test code 37676).

Individuals suitable for testing

  • Individuals eligible for screening (ie, adults ≥18 years old; pregnant persons) or risk-based testing (Table 1)

Methods

  • HBsAg
    • Chemiluminescent "antibody sandwich" immunoassay; confirmation by specific antibody neutralization
    • Analytical sensitivity: 0.085 IU/mL (WHO 1st International Reference Standard 80/549), 0.030 PEI units/mL (ad subtype), 0.019 PEI units/mL (ay subtype)
  • HBsAb
    • Chemiluminescent "antigen sandwich" immunoassay
    • Analytical range: 5-1,000 mIU/mL
  • HBcAb
    • Chemiluminescent immunoassay (total, competitive; IgM, class-capture "sandwich")

Interpretive information

Interpretations of the results from the HBV Triple Screen Panel with Reflexes are summarized in Table 2. Briefly, positive results for HBsAg and HBcAb likely indicate HBV infection; for these patients, the presence of HBcAb IgM indicates an acute infection, and its absence suggests a chronic infection.7 A negative result for HBsAg for patients who have a positive result for HBsAb (≥10 mIU/mL) likely indicates vaccine-mediated immunity. For these patients, the presence of HBcAb indicates immunity owing to natural infection in un-immunized patients, and its absence indicates immunity owing to vaccination.7

Table 2. Interpretation of HBV Screen Serologic Markers

Marker7

Acute infection

Chronic infection

Immunity due to past infection

Immunity due to vaccination

Susceptible to infection

HBsAg

+

+

–

–

–

HBsAb

–

–

+a

+a

–

HBcAb

+

+

+

–

–

HBcAb, IgM

+

–

–

–

–
A minus sign (–) indicates absence of a marker; a plus sign (+) indicates presence of a marker.
HBcAb, hepatitis B core antibody (total IgG and IgM); HBsAb, hepatitis B surface antibody; HBsAg, hepatitis B surface antigen; HBV, hepatitis B virus.
a Immunity requires ≥10 mIU/mL of HBsAb by a quantitative assay.

 

Negative results for all 3 markers (HBsAg, HBsAb, and HBcAb) most likely indicate susceptibility to infection.7

In some situations, HBcAb may be the only detectable marker of HBV infection.4,7 During active infection, mutations in HBsAg can cause negative HBsAg results.8 During resolution of infection, a “window period” can occur during seroconversion when HBsAg has disappeared, but levels of HBsAb are still undetectable.9 An isolated positive result for HBcAb may also be a false-positive result, though this is rare with modern HBcAb assays.4

HBsAg contained in the HBV vaccine can cause transient positive HBsAg results.10 In infants <24 months of age, positive antibody test results can be caused by passive transfer of maternal antibodies.7 In rare cases, heterophilic antibodies can interfere with any of the immunoassays.11

References

  1. Hepatitis B questions and answers for health professionals. Centers for Disease Control and Prevention. Reviewed March 30, 2022. Accessed March 7, 2024. https://www.cdc.gov/hepatitis/hbv/hbvfaq.htm
  2. Hepatitis B surveillance 2021. Centers for Disease Control and Prevention. Updated August 7, 2023. Accessed March 7, 2024. https://www.cdc.gov/hepatitis/statistics/2021surveillance/hepatitis-b.htm#print
  3. 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(11):794. doi:10.7326/m17-1106
  4. 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(4):1560-1599. doi:10.1002/hep.29800
  5. US Preventive Services Task Force; Krist AH, Davidson KW, et al. Screening for hepatitis B virus infection in adolescents and adults. JAMA. 2020;324(23):2415-2422. doi:10.1001/jama.2020.22980
  6. 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(1):1-25. doi:10.15585/mmwr.rr7201a1
  7. Roush S, MT, Beall MB, McGee L, et al. Chapter 22: Laboratory Support for the Surveillance of Vaccine-preventable Diseases. In: Roush SW, Baldy LM, eds. Manual for the Surveillance of Vaccine-Preventable Diseases. Centers for Disease Control and Prevention. Reviewed March 11, 2024. Accessed March 18, 2024. https://www.cdc.gov/vaccines/pubs/surv-manual/chpt22-lab-support.html
  8. Malagnino V, Fofana DB, Lacombe K, Gozlan J. Occult hepatitis B virus infection: an old entity with novel clinical involvements. Open Forum Infect Dis. 2018;5(10):ofy227-. doi:10.1093/ofid/ofy227
  9. Guvenir M, Arikan A. Hepatitis B virus: from diagnosis to treatment. Pol J Microbiol. 2020;69(4):391-399. doi:10.33073/pjm-2020-044
  10. Campioli CC, Garrigos ZE, Assi M, et al. Transient hepatitis B surface antigenemia following immunization with Heplisav-B. Mayo Clin Proc: Innov, Qual Outcomes. 2021;5(3):542-547. doi:10.1016/j.mayocpiqo.2020.10.010
  11. Klingen JT, Mustafayev K, Yibirin M, et al. False-reactive hepatitis B surface antigen test results in cancer patients. Eur J Clin Microbiol Infect Dis. 2023;42(3):383-385. doi:10.1007/s10096-023-04554-4

Content reviewed 04/2024

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This test is used to screen for current or past hepatitis B virus infection and vaccination status.

Test Guide List

HBV Screen Panel With Reflexes

Test Summary

 

HBV Triple Screen Panel With Reflexes

Test code: 39170         

 

Clinical use

  • Screen or test for hepatitis B virus (HBV) infection and assess immune status

Clinical background

HBV is a viral pathogen that infects the liver and causes hepatitis B, an inflammatory liver disease. For unimmunized persons, symptoms of acute hepatitis can range from being asymptomatic or include fever, fatigue, loss of appetite, nausea, vomiting, abdominal pain, dark urine, and jaundice.1 In the United States, an estimated 13,000 people had new HBV infections in 2021.2 Additionally, an estimated 580,000 to 1.17 million people live with CHB,1 about two-thirds of whom do not know they have HBV infection.3 Though most people with CHB are asymptomatic, they remain infectious and have increased risk of life-threatening complications, including cirrhosis and hepatocellular carcinoma.1 Detecting acute and chronic HBV infections is important to prevent further transmission and reduce morbidity and mortality from CHB.

Screening for HBV is recommended for all adults aged 18 years and older at least once in their lifetime and all pregnant persons during each pregnancy.1 Expanded risk-based testing is recommended for people with elevated risk of infection or complications from hepatitis B, those requiring immunosuppressive therapy, and others listed in Table 1.1,3–6 Periodic screening may be appropriate for those with ongoing risk of infection.5,6 In addition to helping connect those with HBV infections to care, testing can also help identify people susceptible to HBV for whom vaccination may be appropriate.1,3,4,6

Table 1. People Suitable for HBV Testing

  • People born in moderately (prevalence ≥2%) or highly endemic areas1,6
  • Unvaccinated children of people born in highly endemic (prevalence ≥8%) areas1,5,6
  • People who have traveled to highly or moderately endemic areas3
  • Pregnant womena
  • Children born to women with HBV infection1,4
  • People who use intravenous drugs (current or past)1,3–6
  • Men who have sex with men1,3–6
  • People who have a history of sexually transmitted infections or high-risk sexual activities1,3–6
  • Household and sexual contacts of people with HBV infection1,3–6
  • Healthcare and public safety workers at risk of exposure to blood-borne pathogens1,4
  • People living or working at facilities for developmentally disabled people1,4–6
  • People who are incarcerated or in detention settings1,3–6
  • People requiring immunosuppressive therapy1,3–6
  • People with end-stage renal disease (receiving dialysis)1,3–6
  • People with hepatitis C virus (HCV) or HIV infection1,3–6
  • People with diabetes who are age 19 to 59 years, if not vaccinated1,4,6
  • Persons with elevated ALT or AST levels of unknown origin
a Testing with a hepatitis B surface antigen (HBsAg) test is recommended with follow-up testing for those with positive results.1,3,4,6

 

For screening, the Centers for Disease Control and Prevention and the American College of Physicians recommend using tests for 3 serologic markers together (ie, a “triple screen”) to help evaluate HBV infection and immune status.1,3,6 These markers include hepatitis B surface antigen (HBsAg), the antibody (HBsAb) to the surface antigen, and the total (IgG and IgM) antibody (HBcAb) to the HBV core antigen. HBsAg is a marker of HBV infection (acute and chronic) and infectiousness7; tests are >98% sensitive and specific for HBV.5 HBsAb is a marker of resolved HBV infection or response to vaccination; titers ≥10 mIU/mL indicate immunity.1,7 HBcAb is a marker of current or past infection; however, IgM is present only during the acute phase of infection.7

HBV Triple Screen Panel with Reflexes (test code 39170) includes a qualitative test for HBsAg, a quantitative test for HBsAb, and a qualitative test for HBcAb. Reflex testing is performed on specimens with positive HBsAg results (to a confirmatory test) and specimens with positive HBcAb results (to an IgM test). Reflex tests are performed at an additional charge with additional CPT codes. Individual components of this panel may be ordered separately (Hepatitis B Surface Antigen with Reflex Confirmation, test code 498; Hepatitis B Surface Antibody Immunity, Quantitative, test code 8475; Hepatitis B Core Antibody, Total, with Reflex to IgM, test code 37676).

Individuals suitable for testing

  • Individuals eligible for screening (ie, adults ≥18 years old; pregnant persons) or risk-based testing (Table 1)

Methods

  • HBsAg
    • Chemiluminescent "antibody sandwich" immunoassay; confirmation by specific antibody neutralization
    • Analytical sensitivity: 0.085 IU/mL (WHO 1st International Reference Standard 80/549), 0.030 PEI units/mL (ad subtype), 0.019 PEI units/mL (ay subtype)
  • HBsAb
    • Chemiluminescent "antigen sandwich" immunoassay
    • Analytical range: 5-1,000 mIU/mL
  • HBcAb
    • Chemiluminescent immunoassay (total, competitive; IgM, class-capture "sandwich")

Interpretive information

Interpretations of the results from the HBV Triple Screen Panel with Reflexes are summarized in Table 2. Briefly, positive results for HBsAg and HBcAb likely indicate HBV infection; for these patients, the presence of HBcAb IgM indicates an acute infection, and its absence suggests a chronic infection.7 A negative result for HBsAg for patients who have a positive result for HBsAb (≥10 mIU/mL) likely indicates vaccine-mediated immunity. For these patients, the presence of HBcAb indicates immunity owing to natural infection in un-immunized patients, and its absence indicates immunity owing to vaccination.7

Table 2. Interpretation of HBV Screen Serologic Markers

Marker7

Acute infection

Chronic infection

Immunity due to past infection

Immunity due to vaccination

Susceptible to infection

HBsAg

+

+

–

–

–

HBsAb

–

–

+a

+a

–

HBcAb

+

+

+

–

–

HBcAb, IgM

+

–

–

–

–
A minus sign (–) indicates absence of a marker; a plus sign (+) indicates presence of a marker.
HBcAb, hepatitis B core antibody (total IgG and IgM); HBsAb, hepatitis B surface antibody; HBsAg, hepatitis B surface antigen; HBV, hepatitis B virus.
a Immunity requires ≥10 mIU/mL of HBsAb by a quantitative assay.

 

Negative results for all 3 markers (HBsAg, HBsAb, and HBcAb) most likely indicate susceptibility to infection.7

In some situations, HBcAb may be the only detectable marker of HBV infection.4,7 During active infection, mutations in HBsAg can cause negative HBsAg results.8 During resolution of infection, a “window period” can occur during seroconversion when HBsAg has disappeared, but levels of HBsAb are still undetectable.9 An isolated positive result for HBcAb may also be a false-positive result, though this is rare with modern HBcAb assays.4

HBsAg contained in the HBV vaccine can cause transient positive HBsAg results.10 In infants <24 months of age, positive antibody test results can be caused by passive transfer of maternal antibodies.7 In rare cases, heterophilic antibodies can interfere with any of the immunoassays.11

References

  1. Hepatitis B questions and answers for health professionals. Centers for Disease Control and Prevention. Reviewed March 30, 2022. Accessed March 7, 2024. https://www.cdc.gov/hepatitis/hbv/hbvfaq.htm
  2. Hepatitis B surveillance 2021. Centers for Disease Control and Prevention. Updated August 7, 2023. Accessed March 7, 2024. https://www.cdc.gov/hepatitis/statistics/2021surveillance/hepatitis-b.htm#print
  3. 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(11):794. doi:10.7326/m17-1106
  4. 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(4):1560-1599. doi:10.1002/hep.29800
  5. US Preventive Services Task Force; Krist AH, Davidson KW, et al. Screening for hepatitis B virus infection in adolescents and adults. JAMA. 2020;324(23):2415-2422. doi:10.1001/jama.2020.22980
  6. 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(1):1-25. doi:10.15585/mmwr.rr7201a1
  7. Roush S, MT, Beall MB, McGee L, et al. Chapter 22: Laboratory Support for the Surveillance of Vaccine-preventable Diseases. In: Roush SW, Baldy LM, eds. Manual for the Surveillance of Vaccine-Preventable Diseases. Centers for Disease Control and Prevention. Reviewed March 11, 2024. Accessed March 18, 2024. https://www.cdc.gov/vaccines/pubs/surv-manual/chpt22-lab-support.html
  8. Malagnino V, Fofana DB, Lacombe K, Gozlan J. Occult hepatitis B virus infection: an old entity with novel clinical involvements. Open Forum Infect Dis. 2018;5(10):ofy227-. doi:10.1093/ofid/ofy227
  9. Guvenir M, Arikan A. Hepatitis B virus: from diagnosis to treatment. Pol J Microbiol. 2020;69(4):391-399. doi:10.33073/pjm-2020-044
  10. Campioli CC, Garrigos ZE, Assi M, et al. Transient hepatitis B surface antigenemia following immunization with Heplisav-B. Mayo Clin Proc: Innov, Qual Outcomes. 2021;5(3):542-547. doi:10.1016/j.mayocpiqo.2020.10.010
  11. Klingen JT, Mustafayev K, Yibirin M, et al. False-reactive hepatitis B surface antigen test results in cancer patients. Eur J Clin Microbiol Infect Dis. 2023;42(3):383-385. doi:10.1007/s10096-023-04554-4

Content reviewed 04/2024

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