Difference Between Hepatitis B Surface Antigen Quantification and Hepatitis B Surface Antibody
Hepatitis B surface antigen (HBsAg) quantification measures active viral presence indicating current infection, while Hepatitis B surface antibody (HBsAb) indicates immunity to HBV from either vaccination or resolved natural infection. 1, 2
Hepatitis B Surface Antigen (HBsAg)
HBsAg is a glycoprotein on the surface of the hepatitis B virus that serves as the hallmark of active HBV infection, appearing 1-10 weeks before symptom onset in acute infection 2
HBsAg positivity indicates current HBV infection (either acute or chronic) and confirms that the person is infectious 1, 2
Persistence of HBsAg beyond 6 months indicates progression to chronic HBV infection 1, 2
Quantification of HBsAg levels (HBsAg quant) can be used for: 1, 3
- Staging the natural history of HBV infection
- Evaluating response to therapy
- Predicting risk of hepatocellular carcinoma (HCC)
- Predicting likelihood of HBsAg loss during treatment
Low levels of both HBV DNA (<2000 IU/mL) and HBsAg (<1000 IU/mL) are associated with decreased risk of HCC 1
During peginterferon alfa therapy, absence of decline in HBsAg by week 12 predicts non-response and may justify stopping therapy 1
Hepatitis B Surface Antibody (HBsAb)
- HBsAb indicates recovery from and immunity to HBV infection, resulting from either natural infection or vaccination 1
- In most patients with self-limited acute HBV infection, HBsAg and HBsAb are not detectable simultaneously 1
- Detection of HBsAb in the absence of HBc total antibodies distinguishes vaccine-derived immunity from immunity acquired by natural infection (in which both HBs antibody and HBc total antibodies are present) 1
- Current commercially available assays for detecting HBsAb yield positive results when antibody levels are ≥10 mIU/mL, indicating protective immunity 1, 4
- HBsAb levels often fluctuate and decrease over time, potentially requiring booster vaccination in certain populations 5
Clinical Interpretation of Combined Results
- HBsAg positive + Total anti-HBc positive + IgM anti-HBc positive = Acute HBV infection 2
- HBsAg positive + Total anti-HBc positive + IgM anti-HBc negative = Chronic HBV infection 2
- HBsAg negative + Total anti-HBc positive + Anti-HBs positive = Resolved HBV infection with natural immunity 6, 2
- HBsAg negative + Anti-HBc negative + Anti-HBs positive = Immunity from vaccination 2
- HBsAg negative + Anti-HBc negative + Anti-HBs negative = Never infected, susceptible to infection 2
- HBsAg negative + Total anti-HBc positive + Anti-HBs negative = Several possibilities: 6
- Resolved infection with waning antibody levels
- False positive anti-HBc
- "Window period" of acute infection
- Occult HBV infection (especially in immunocompromised patients)
Special Considerations
Occult HBV Infection
- Occult HBV infection can occur when HBsAg is undetectable despite the presence of HBV DNA in serum or liver tissue 2, 7
- This is particularly important in immunocompromised patients with unexplained elevation of serum aminotransferase levels 1
- HCC can still develop in the absence of detectable HBsAg in serum 7
Risk of HBV Reactivation
- Patients who are HBsAg negative but anti-HBc positive have a 3-45% risk of HBV reactivation when receiving immunosuppressive therapy 1, 6
- The risk is particularly high with anti-CD20 monoclonal antibodies (e.g., rituximab) 1, 6
- Antiviral prophylaxis should be considered for HBsAg-positive or HBcAb-positive patients undergoing immunosuppressive therapy 1
Pitfalls in Interpretation
- Passively acquired HBsAb (e.g., from transfusion) may not indicate true immunity 8
- Transient HBsAg positivity can occur up to 18 days following vaccination (up to 52 days in hemodialysis patients) 2
- False-negative HBsAg results may occur in chronic liver disease; viral load measurement should be considered in patients with a history of hepatitis 1