Initial Testing for Hepatitis B
Order a three-test panel consisting of hepatitis B surface antigen (HBsAg), hepatitis B surface antibody (anti-HBs), and total hepatitis B core antibody (anti-HBc) as the baseline serologic assessment for hepatitis B status. 1, 2
Standard Testing Panel
The initial diagnostic workup requires these three specific tests 1:
HBsAg (Hepatitis B surface antigen): Identifies active infection, whether acute or chronic. This is the hallmark marker of HBV infection and the first serologic marker to appear, typically detectable within 30 days of exposure (range: 6-60 days). 3
Anti-HBs (Hepatitis B surface antibody): Indicates immunity from either vaccination or past cleared infection. 1, 2
Total anti-HBc (Hepatitis B core antibody): Distinguishes natural infection from vaccine-induced immunity, as it appears with infection but not after vaccination. This marker persists for life in the majority of persons who have been infected. 3, 1
Interpretation Algorithm
After obtaining the three-test panel, interpret results as follows 2:
All three negative: Patient is susceptible to HBV and needs vaccination 1
HBsAg positive: Active HBV infection is present (acute or chronic). Immediately add HBV DNA quantitative viral load testing to assess replication status. 1, 2
HBsAg negative, anti-HBc positive, anti-HBs positive: Resolved past infection with immunity 2
HBsAg negative, anti-HBc negative, anti-HBs positive: Vaccine-induced immunity 2, 4
Isolated anti-HBc positive (HBsAg negative, anti-HBs negative): This pattern requires careful interpretation and may represent waning anti-HBs after remote infection, occult hepatitis B, or false-positive reaction. Consider quantitative HBV DNA testing to rule out occult infection. 3, 1, 2
When to Add IgM Anti-HBc
Do not order IgM anti-HBc for routine screening. 2 This test should only be added when acute hepatitis B is specifically suspected based on clinical evidence of acute hepatitis or epidemiologic link to HBV exposure. 3 IgM anti-HBc appears at the onset of symptoms and persists for up to 6 months if infection resolves, distinguishing acute from chronic infection. 3
Additional Testing for Confirmed Infection
If HBsAg is confirmed positive, order these additional tests to guide management 2, 4:
HBeAg and anti-HBe: HBeAg positivity indicates high viral replication (typically 10^6-10^10 IU/mL), while anti-HBe positivity generally indicates lower replication levels (0-10^5 IU/mL). 3, 2
HBV DNA quantitative: Essential for assessing viral replication level and treatment decisions 2, 4
ALT/AST: To assess liver inflammation and disease activity 4
Critical Pitfalls to Avoid
Never rely solely on HBsAg for comprehensive screening, as this will miss past infections and immunity status. 2
Do not assume vaccination history eliminates testing need, as breakthrough infections can occur and vaccination status may be unreliable. 2
Avoid ordering IgM anti-HBc routinely, as its positive predictive value is low in asymptomatic persons and it should be limited to those with clinical evidence of acute hepatitis. 3, 2
Do not interpret isolated anti-HBc as definitively indicating occult infection without confirmatory HBV DNA testing, as this pattern is common in low-prevalence populations and often represents false-positive reactions or waning anti-HBs. 3, 2
Use FDA-licensed HBsAg tests and perform confirmatory neutralizing testing on initially reactive specimens to avoid false positives. 3
Special Populations Requiring Testing
The CDC recommends universal screening for all adults aged 18 years and older using this three-test strategy. 1 Priority populations include 3:
- Persons born in regions with HBsAg prevalence >2% (much of Eastern Europe, Asia, Africa, Middle East, Pacific Islands) 3
- Pregnant women 3
- Hemodialysis patients 3
- HIV-positive persons 3
- Men who have sex with men and injection drug users (test before vaccination) 3
- Persons starting immunosuppressive or cytotoxic therapy 3, 2
- Persons with unexplained ALT elevations 3