Hepatitis B Serology Testing
Order a three-test panel consisting of hepatitis B surface antigen (HBsAg), total or IgG antibody to hepatitis B core antigen (anti-HBc), and antibody to hepatitis B surface antigen (anti-HBs) for comprehensive hepatitis B screening. 1
Core Testing Panel
The standard hepatitis B serology panel includes three essential markers that together distinguish between active infection, resolved infection, immunity from vaccination, and susceptibility 2:
HBsAg (Hepatitis B Surface Antigen): Detects active infection (both acute and chronic). This is the hallmark marker of HBV infection and the first to appear, typically within 30 days of exposure (range 6-60 days) 2
Anti-HBc total or IgG (Antibody to Hepatitis B Core Antigen): Indicates previous or ongoing infection. This marker persists for life in the majority of persons after HBV exposure and distinguishes natural infection from vaccine-induced immunity 2, 1
Anti-HBs (Antibody to Hepatitis B Surface Antigen): Indicates immunity from either vaccination or resolved infection 2, 1
Interpretation Algorithm
The combination of these three tests provides definitive diagnostic information 1, 3:
| HBsAg | Anti-HBc | Anti-HBs | Interpretation |
|---|---|---|---|
| Positive | Positive | Negative | Active chronic HBV infection |
| Negative | Positive | Positive | Resolved past infection |
| Negative | Negative | Positive | Immunity from vaccination |
| Negative | Positive | Negative | Isolated core antibody (possible occult HBV) |
| Negative | Negative | Negative | Susceptible (needs vaccination) |
Additional Testing When HBsAg is Positive
If HBsAg is positive, immediately order HBeAg, anti-HBe, and quantitative HBV DNA to assess disease activity and guide treatment decisions. 2, 1
- HBeAg positivity typically indicates high viral replication and increased infectivity 2
- Quantitative HBV DNA is essential for determining treatment eligibility and monitoring response 2
- ALT levels should be assessed to evaluate liver inflammation 2
Additional Testing for Isolated Anti-HBc
If the pattern shows isolated anti-HBc positivity (HBsAg negative, anti-HBc positive, anti-HBs negative), order quantitative HBV DNA testing to rule out occult HBV infection, particularly in immunocompromised patients or those with unexplained elevated aminotransferases 2, 1, 3
Critical Pitfalls to Avoid
Do NOT order only HBsAg: This single test will miss resolved infections, vaccine immunity status, and isolated core antibody patterns 1
Do NOT order IgM anti-HBc for routine screening: Reserve this test exclusively for suspected acute hepatitis B (clinical symptoms or epidemiologic link to infection). The positive predictive value is low in asymptomatic persons 2
Do NOT assume vaccination history eliminates testing need: Breakthrough infections can occur, and documented vaccination history is often unreliable 1
Do NOT interpret isolated anti-HBc definitively without HBV DNA testing: This pattern requires further evaluation as it may represent occult infection, particularly in immunocompromised patients 2, 1, 3
Do NOT delay testing in patients starting immunosuppressive therapy or chemotherapy: Complete serologic assessment is essential before initiating these treatments to assess reactivation risk, but do not delay cancer therapy while awaiting results 1
Special Clinical Contexts
For patients with chronic liver disease from other causes (such as hepatitis C), the same three-test panel is recommended to determine if hepatitis B vaccination is needed, as coinfection significantly increases morbidity and mortality 4
For healthcare workers or those with occupational exposure, testing both anti-HBs and anti-HBc distinguishes vaccine-induced immunity from infection-induced immunity 3