What does a negative Hepatitis B (Hep B) surface antigen result indicate?

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Last updated: May 25, 2025View editorial policy

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From the Guidelines

A negative Hepatitis B surface antigen (HBsAg) test indicates that you do not currently have an active Hepatitis B infection, but additional tests are recommended to fully understand your immunity or past exposure status, including Hepatitis B surface antibody (anti-HBs) and Hepatitis B core antibody (anti-HBc) 1. To determine the next steps, it's essential to consider the results of these additional tests.

  • If you've never been infected or vaccinated, you should consider getting the Hepatitis B vaccine series, which consists of 2-3 doses over 6 months depending on the specific vaccine used, as recommended by the 2021 guidelines 1.
  • The vaccine is highly effective at preventing Hepatitis B infection, which can cause serious liver problems including cirrhosis and liver cancer.
  • If you've previously been vaccinated but are unsure of your immunity status, the anti-HBs test can confirm whether you have protective antibodies.
  • Regular screening is important for those at higher risk, including healthcare workers, people who inject drugs, men who have sex with men, and individuals with multiple sexual partners, as emphasized in the 2014 guidelines for HIV-infected patients 1.
  • It's also important to note that a negative HBsAg test does not necessarily mean you are immune to Hepatitis B, and further testing may be necessary to determine your immunity status, as discussed in the 2020 update on hepatitis B virus screening and management for patients with cancer prior to therapy 1.

From the Research

Hepatitis B Surface Antigen Negative

  • A negative result for serum HBsAg tests does not always represent a clearance or inactivating status of HBV viruses, as HCC could still develop in the absence of detectable HBsAg in serum, known as occult hepatitis B virus infection (OBI) 2.
  • OBI is characterized by the presence of HBV viral genome in the patient's liver but no virus surface antigen (HBsAg) detected in serum by commonly used immunoassays 2.
  • The duration of HBV replication and its pathological consequences last much longer in OBI than in overt infections 2.

HBsAg and HCC Risk

  • Higher levels of HBsAg are usually connected with a higher risk of developing HCC, while lower levels of HBsAg are usually connected with a lower risk 2.
  • The serum levels of HBsAg, along with HBV DNA levels, are the most important predictors of the risk of developing HCC 2.

HBsAg and Vaccination

  • Administration of HBIG with HepB can delay and reduce responses to HepB in mice, regardless of the site of administration 3.
  • Lower levels of antibody to HBV surface antigen (anti-HBs) were observed at the end of the 3-dose series in all groups of newborn mice that received HepB and HBIG 3.

Differentiation of CHB and IC

  • A cutoff value of HBsAg level at 1000IU/mL was more reliable for diagnosis of CHB with 82.7% sensitivity and 66.2% specificity than other HBsAg cutoff values 4.
  • Single-point HBsAg quantification did not have enough sensitivity and specificity for differentiation of HBeAg-negative CHB and IC state 4.

Related Questions

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Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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