Hepatitis B (HBV)

Suspected acute HBV infection

The rate of spontaneous recovery from acute HBV infection varies, depending on the patient’s age at the time of acquisition and the patient’s immune status. Only 5 – 20 % of immunocompetent adults infected with HBV remain chronically infected, whereas up to 90 % of infected infants will remain chronically infected.

Marker Definition and diagnostic use
HBsAg
  • General marker of HBV infection
  • First serologic marker to appear
  • Persistence for >6 months refers to chronic HBV infection
anti-HBs
  • Neutralizing antibody
  • Develops in response to HBV vaccination and during recovery from acute hepatitis B, indicating past infection and immunity
  • Only marker detectable after immunity conferred by HBV vaccination
anti-HBc IgM
  • Present during acute HBV infection and usually disappears within 6 months
  • 10 – 20 % of chronically infected with hepatitis flares may also be positive for anti-HBc IgM
anti-HBc
  • Indicates a prior exposure to HBV. Infection may be resolved (HBsAg negative) or ongoing (HBsAg positive).
  • Not a neutralizing antibody
  • Isolated anti-HBc IgG may indicate occult HBV infection
HBeAg
  • Active replication of HBV and high risk of transmission
anti-HBe
  • Marker of less active HBV replication
  • Indicates decrease of HBV infectivity and remission of disease
  • Precore/core promoter mutations in HBV genome
HBV DNA
  • Marker of viral replication
  • Marker of disease progression in chronic HBV infection
  • Used to determine the status of chronic HBV infection in combination with HBsAg and HBeAg, by differentiating between active and inactive disease states

Adapted from:

  1. Fourati S and Pawlotsky JM. Recent advances in understanding and diagnosing hepatitis B virus infection. F1000Res. 2016;5:F1000 Faculty Rev-2243.
  2. Mauss S, Berg T, Rockstroh J, Sarrazin C, and Wedemeyer H. Hepatology - A clinical textbook (10th ed.). Medizin Fokus Verlag;2020. [Internet; cited 2023 Nov 14]. Available from: https://www.hepatologytextbook.com/.
  3. Liaw YF, Chu CM. Hepatitis B virus infection. Lancet. 2009;373:582-592.
  4. Davison SA and Strasser SI. Ordering and interpreting hepatitis B serology. BMJ. 2014;348: g2522.
  5. Shiffman ML. Management of Acute Hepatitis B. Clin Liv Dis. 2010;14:75-91.
  6. ARUP Consult. Hepatitis B Virus Testing. [Internet; updated 2020 Feb; cited 2023 Nov 14]. Available from: https://arupconsult.com/sites/default/files/Hepatitis%20B%20Virus%20Testing%20algorithm.pdf.
  7. Kramvis A, Chang KM, Dandri M, et al. A roadmap for serum biomarkers for hepatitis B virus: current status and future outlook. Nat Rev Gastroenterol Hepatol. 2022;19:727-45.
Product Description Tests Product page
Elecsys® Anti-HBc IgM a) Electrochemiluminescence immunoassay (ECLIA) for the qualitative detection of IgM class antibodies to the hepatitis B core antigen (HBcAg) in human serum and plasma 100
Elecsys® Anti-HBc IgM b) 300
Elecsys® Anti-HBc II a) Electrochemiluminescence immunoassay (ECLIA) for the qualitative detection of IgM and IgG class antibodies to the hepatitis B core antigen (HBcAg) in human serum and plasma 100
Elecsys® Anti-HBc II b) 300
Elecsys® Anti-HBe a) Electrochemiluminescence immunoassay (ECLIA) for the qualitative detection of total antibodies to the hepatitis B e antigen (HBeAg) in human serum and plasma 100
Elecsys® Anti-HBe b) 300
Elecsys® HBeAg a) Electrochemiluminescence immunoassay (ECLIA) for the qualitative detection of the hepatitis B e antigen (HBeAg) in human serum and plasma 100
Elecsys® HBeAg b) 300
Elecsys® HBeAg quant a) Immunoassay for the in vitro qualitative and quantitative determination of hepatitis B e antigen (HBeAg) in human serum and plasma. 100
Elecsys® HBeAg quant b) 300
Elecsys® Anti-HBs II a) Electrochemiluminescence immunoassay (ECLIA) for the quantitative determination of antibodies to the hepatitis B surface antigen (HBsAg) in human serum and plasma 100
Elecsys® Anti-HBs II b) 300
Elecsys® HBsAg Confirmatory Test a) b) Electrochemiluminescence immunoassay (ECLIA) for the qualitative detection of the hepatitis B surface antigen (HBsAg) in human serum and plasma
Elecsys® HBsAg II Auto Confirm b) Electrochemiluminescence immunoassay (ECLIA) for the confirmation of presence of the hepatitis B surface antigen (HBsAg) in human serum and plasma 100
Elecsys® HBsAg II quant II a) Electrochemiluminescence immunoassay (ECLIA) for the quantitative determination of the hepatitis B surface antigen (HBsAg) in human serum and plasma 100
Elecsys® HBsAg II quant II b) 100
cobas® HBV c) Nucleic acid amplification test for the quantitative measurement of HBV DNA in human EDTA plasma 120
cobas® HBV d) 96
192

a) for use on the cobas® e 411 analyzer and the cobas® e 601 / 602 modules
b) for use on the cobas® e 402 and cobas® e 801 analytical units
c) for use on the cobas® 4800 System
d) for use on the cobas® 6800/8800 Systems

Adapted from:

  1. Petersen J. Hepatitis B diagnostic tests. In: Mauss S, Berg T, Rockstroh J, Sarrazin C, and Wedemeyer H (Eds.), Hepatology – A clinical textbook (10th ed., pp. 151-62). Medizin Fokus Verlag;2020. Available at: https://www.hepatologytextbook.com/.
  2. ARUP Consult. Hepatitis B Virus Testing. [Internet; updated 2020 Feb; cited 2023 Nov 14]. Available from: https://arupconsult.com/sites/default/files/Hepatitis%20B%20Virus%20Testing%20algorithm.pdf.
  3. Fourati S and Pawlotsky JM. Recent advances in understanding and diagnosing hepatitis B virus infection. F1000Res. 2016;5:F1000 Faculty Rev-2243.
  4. Davison SA and Strasser SI. Ordering and interpreting hepatitis B serology. BMJ. 2014;348: g2522.
  5. Shiffman ML. Management of Acute Hepatitis B. Clin Liv Dis. 2010;14:75-91.
  6. Liaw YF, Chu CM. Hepatitis B virus infection. Lancet. 2009;373:582-592.
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Step 1

Perform anti-HBc IgM and HBsAg tests in parallel*

anti-HBc IgM
HBsAg

*included in acute hepatitis test panel with anti-HAV IgM, anti-HCV, and anti-HEV IgM tests

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Step 2

Perform HBeAg and HBV DNA tests

HBeAg test

HBV DNA test
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Step 2

Perform repeat HBsAg test

HBsAg test
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Step 3

Perform HBsAg confirmatory test

HBsAg confirmatory test
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Step 4

Perform anti-HBc and anti-HBc IgM tests

anti-HBc test
anti-HBc IgM test
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Summary

Susceptible to infection
Vaccination recommended

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Summary

Immune due to Vaccination
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Summary

Immune due to resolved natural infection
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Summary

Interpretation unclear
Evaluation of individuals with isolated anti-HBc schould include repeat testing for anti-HBc, HBsAg, anti-HBe, anti-HBs, anto-HBc IgM, and if possible HBV DNS to exclude low-level chronic HBC infection.
Confirmation of isolated anti-HBc results is difficult, as there is no commercially available confirmation test for anti-HBc available. Resolution can be achived on basis of 2:1 decision using 3 different anti-HBc tests with similar sensitivity.

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Summary

Interpretation unclear
Evaluation of individuals with isolated anti-HBc schould include repeat testing for anti-HBc, HBsAg, anti-HBe, anti-HBs, anto-HBc IgM, and if possible HBV DNS to exclude low-level chronic HBC infection.
Confirmation of isolated anti-HBc results is difficult, as there is no commercially available confirmation test for anti-HBc available. Resolution can be achived on basis of 2:1 decision using 3 different anti-HBc tests with similar sensitivity.

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Summary

Chronic HBV infection
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Summary

Possible acute HBV infection: window phase
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Summary

Confirmed acute HBV infection
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Summary

Infection probably resolving
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Summary

Consider acute hepatitis A, C or E infection, or other etiologies
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Summary

No chronic HBV infection
In rare cases, the absence of HBsAg could be related to the sensitivity of the test used for detection, either in therms of analytical sensitivity or variant detection.

Consider testing for anti-HBs and anti-HBc to determine immunity to HBV in case of anti-HBc-only reactive, consider/monitor potential risk of reactivation (e.g. in case of immunosuppression).

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Summary

Non-specific HBsAg reactivity
Consider testing other markers (anti HBs, anti-HBc IgM, anti-HBc, HBeAg, anti-HBe, HBV DNA)

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Summary

Uncertain status, further testing required
Perform quantitative HBsAg, HBeAg (quant), anti-HBe, and HBV DNA test to clarify phase of infection and whether to treat.

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Summary

Early infection
Perform quantitative HBsAg, HBeAg (quant), anti-HBe, and HBV DNA test to clarify phase of infection and whether to treat.

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Summary

Non-recent infection Perform quantitative HBsAg, HBeAg (quant), anti-HBe, and HBV DNA test to clarify phase of infection and whether to treat.

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Summary

Recent infection or exacerbation of chronic disease
Perform quantitative HBsAg, HBeAg (quant), anti-HBe, and HBV DNA test to clarify phase of infection and whether to treat.

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Summary

Recent infection or exacerbation of chronic disease
Perform quantitative HBsAg, HBeAg (quant), anti-HBe, quantitative anti-HBc, and HBV DNA test to clarify phase of infection and whether to treat.

Back
Next Restart simulation
Step
Result
Interpretation
1
anti-HBc IgM test = ...
HBsAg test = ...
waiting for input
1
anti-HBc IgM test = negative
HBsAg test = negative
1
anti-HBc IgM test = negative
HBsAg test = positive
Suspected chronic HBV Infection.

Repeat HBsAg test within 6 weeks.

Consider testing other HBV markers.
1
anti-HBc IgM test = positive
HBsAg test = negative

Infection probably resolving

1
anti-HBc IgM test = positive
HBsAg test = positive
Acute HBV infection.

Repeat HBsAg test in 4-6 weeks; consider optional testing of other HBV markers (anti-HBs, HBeAg, HBV DNA)

Upon repeat testing, if HBsAg and Anti-HBc IgM are negative and Anti-HBs is positive, resolved or immune controlled acute infection can be assumed.
2

HBeAg test = ...
HBV DNA test = ...

waiting for input
2

HBeAg test = negative
HBV DNA test = negative

Unlikely patient result.

Possible next steps include repeating the initial tests, assessing additional HBV markers for a comprehensive view, and rigorously checking for any potential sample mix-up or analytical errors.

2

HBeAg test = negative
HBV DNA test = positive

Possible acute HBV infection: window phase

2

HBeAg test = positive
HBV DNA test = negative

Infection probably resolving. 

2

HBeAg test = positive
HBV DNA test = positive

Confirmed acute HBV infection

2
HBsAg test = ...
waiting for input
2
HBsAg test = negative
No chronic HBV infection.
2
HBsAg test = positive

Presumed ongoing infection.

3
HBsAg confirmatory test = ...
waiting for input
3
HBsAg confirmatory test = negative
Non-specific HBsAg reactivity.
3
HBsAg confirmatory test = positive
Infection with HBV confirmed.

Perform anti-HBc and anti-HBc IgM tests.
4
anti-HBc test = ...
anti-HBc IgM test = ...
waiting for input
4
anti-HBc test = negative
anti-HBc IgM test = negative
Uncertain status, further testing required.
4
anti-HBc test = negative
anti-HBc IgM test = positive
Early infection.
4
anti-HBc test = positive
anti-HBc IgM test = negative
Non-recent infection.
4
anti-HBc test = positive
anti-HBc IgM test = positive
Recent infection or exacerbation of chronic disease.
End of test sequence