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Hepatitis B Surface Antigen, Quantitative, Monitoring

Test code(s) 94333

Quantitation of HBsAg may be helpful in differentiating phases of HBV infection, evaluating prognosis (to date, most data has been for patients with hepatitis B envelope antigen [HBeAg]-negative genotype B or C infection), monitoring response to treatment with pegylated interferon (peg-IFN) or nucleos(t)ide analogs (NAs), and guiding decisions on treatment duration.

Qualitative HBsAg testing is recommended to screen patients at risk for HBV infection and is the test recommended for initial diagnosis. It may also be useful to determine vaccine responses for selected patients. In contrast, quantitative HBsAg testing is not recommended for initial diagnosis, but it is useful for disease and treatment monitoring (see Question 1).

Serum HBsAg levels reflect the transcriptional activity of intrahepatic HBV covalently closed circular DNA (cccDNA), an indicator of viral protein synthesis.

Phases of HBV infection are 1) immune-tolerant, 2) immune-active, 3) inactive chronic (inactive carrier), 4) immune-escape (HBeAg-negative chronic), and 5) reactivation. Alanine aminotransferase (ALT) and HBV DNA levels can be helpful in differentiating the phases of HBV infection:

  • Immune-tolerant phase: ALT levels are normal; HBV DNA levels are high.
  • Immune-active phase: ALT levels can be high or intermittently high; HBV DNA levels can fluctuate.
  • Inactive chronic hepatitis (inactive carrier) phase: ALT levels are normal and HBV DNA levels are low or undetectable.
  • Immune-escape phase (HBeAg-negative chronic hepatitis): ALT levels are elevated or may fluctuate; HBV levels tend to be moderate or high.
  • Reactivation phase: ALT levels are elevated; HBV levels tend to be moderate or high.

However, because of the overlap in ALT and HBV DNA patterns between phases, these markers are not sufficient to identify the exact phase of disease.13 Analysis of multiple markers of HBV infection will be helpful in determining disease phase and potential treatment options. Quantitative HBsAg determination and HBeAg status may be additional markers that can be useful for prognosis and therapeutic decision-making in patients with different phases of infection. For example, HBeAg-negative patients with low HBV DNA (<2000 IU/mL), low HBsAg (<1000 IU/mL), and selected genotypes may be considered to be in the inactive carrier state.2 Low serum HBsAg levels measured 1 year after documented HBeAg seroconversion may predict subsequent HBsAg loss in genotype B or C infection.5 Conversely, lack of HBsAg decline and modest (<2 log) reduction in HBV DNA after the third month of antiviral treatment has been suggested as a stopping rule in HBeAg-negative patients with genotype D.6,7 Like HBV DNA levels, HBsAg and HBeAg levels are typically highest in the immune-tolerant phase, decline in the immune-active phase, and are generally lowest in the inactive carrier phase.

Quantitative HBsAg results, along with selected immunologic and virologic characteristics, may help differentiate infection phases and inform prognosis and therapeutic decision-making. For example, the HBeAg-negative inactive carrier state may be identified by low HBV DNA (<2000 IU/mL) and low HBsAg (<1000 IU/mL) in patients with certain genotypes.2 Low serum HBsAg levels measured 1 year after documented HBeAg seroconversion may predict subsequent HBsAg loss in HBV genotype B or C infection.5 It has been documented that a drop in HBsAg levels in patients who are on NA treatment can predict subsequent HBsAg loss. The observed decrease in HBsAg concentration may help predict HBsAg loss and support the decision to discontinue peg-IFN and/or NA therapy.

Peg-interferon and/or NA treatment may lead to reductions in HBsAg. In general, sustained responders display greater and/or more rapid HBsAg decline than non-responders.1-2,4-6 The quantitative HBsAg level that best predicts sustained virologic response (or “cure”) has yet to be well established. However, some experts consider 2 or more measurements of HBsAg below the assay’s lower limit of detection (<0.05 IU/mL) obtained ≥6 months apart to be a potentially useful endpoint for antiviral therapy.9-11

Overall, there is close agreement between the two assays. They have similar lower limits of detection: 0.085 IU/mL for qualitative HBsAg and 0.05 IU/mL for quantitative HBsAg.

No. For most patients, both tests are needed to monitor chronic HBV infection status and response to therapy. Lacking further data, quantitative HBsAg may be used in conjunction with HBV DNA monitoring and other appropriate laboratory testing.1

Published data show some concordance between these 2 assays in individual patients. However, some patients have high levels of HBsAg but decreasing, low, or undetectable HBV DNA. This discordance may be related to differences in disease phase: HBsAg levels can be high because of active transcription of cccDNA, while HBV DNA levels decrease or become undetectable because of decreasing DNA replication. Therefore, measurement of both HBsAg and HBV DNA can provide a more accurate clinical profile for an individual patient and help monitor and predict treatment outcomes. The information gained with both results, even if discordant, can provide additional insights into the patient’s prognosis.

Quest Diagnostics uses an immunoassay method for quantitative HBsAg testing. The method employs the Ortho Vitros® system to construct a standard curve for the quantitative result calculation. The WHO 3rd International standard reference serum (HBV genotype B4, HBsAg subtypes ayw1/adw2) was used to verify the values established for the calibration standard. Results are reported in IU/mL. 


  1. Wong G, Chan H. Use of quantitative hepatitis B surface antigen with hepatitis B virus DNA in clinical practice. Clin Liver Dis. 2013;2:8-10.
  2. Henry Lik-Yuen Chan HL, Thompson A, Martinot-Peignoux M, et al. Hepatitis B surface antigen quantification: why and how to use it in 2011—a core group report. J Hepatol. 2011;55:1121–1131.
  3. Edouard Tuaillon , Anne-Marie Mondain, Nicolas Nagot, et al. Comparison of serum HBsAg quantitation by four immunoassays, and relationships of HBsAg level with HBV replication and HBV genotypes. PLoS One. 2012;7:e32143.
  4. Andersson KL, Chung RT. Monitoring during and after antiviral therapy for hepatitis B. Hepatology. 2009;49:S166–S173.
  5. Tseng T, Liu C, Su T, et al. Serum hepatitis B surface antigen levels predict surface antigen loss in hepatitis B e antigen seroconverters. Gastroenterology. 2011;141:517–525.
  6. Kranidiotia H, Manolakopoulosb S, Khakooa SI. Outcome after discontinuation of nucleot(s)ide analogues in chronic hepatitis B: relapse rate and associated factors. Ann Gastroenterol. 2015;28:173-181.
  7. Lee JM, Ahn SH, Kim HS, et al. Quantitative hepatitis B surface antigen and hepatitis B e antigen titers in prediction of treatment response to entecavir. Hepatology. 2011;53:1486-1493.
  8. Centers for Disease Control and Prevention. Hepatitis B, chronic 2012 case definition. Accessed November 3, 2016.
  9. Sonneveld MJ, Rijckborst V, Boucher C, et al. Prediction of sustained response to peginterferon alfa-2b for hepatitis B e antigen–positive chronic hepatitis B using on-treatment hepatitis B surface antigen decline. Hepatology. 2010; 52: 1251–1257.
  10. Seth AK. HBsAg quantification in clinical practice. J Clin Exp Hepatol. 2012;2:75-80.
  11. Sarin S, Kumar M, Lau G, et al. Asian-Pacific clinical practice guidelines on the management of hepatitis B: a 2015 update. Hepatol Int. 2016;10:1-98.
  12. Höner Zu Siederdissen C, Cornberg M. The role of HBsAg levels in the current management of chronic HBV infection. Ann Gastroenterol. 2014;27:105-112.
  13. World Health Organization (WHO). Guidelines for the prevention, care and treatment of persons with chronic hepatitis B infection. Geneva, Switzerland: WHO; 2015. Accessed June 6, 2017.


This FAQ is provided for informational purposes only and is not intended as medical advice. A clinician’s test selection and interpretation, diagnosis, and patient management decisions should be based on his/her education, clinical expertise, and assessment of the patient.

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Effective 08/01/2017 to present