Hepatitis B: Making Sense of Serology

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What serology tests are available for HBV?

A common point of confusion with hepatitis B virus (HBV) is interpretation of serology testing, the results of which vary depending on the clinical situation (e.g. acute / chronic / resolved infection, prior vaccination, etc.) For our purposes, we are interested in the antigens and corresponding antibodies listed in the figure below.

Source: Zero To Finals, “Understanding Hepatitis B Serology Results”
Source: Immunize Action Coalition, Hepatitis B Vaccine – Ask the Experts
  • HBcAg is not measurable in the blood, thus we can’t test for it on serology
  • The virologist who discovered HBeAg chose the letter e for enigma
  • An “acute hepatitis panel” in Epic at our hospitals includes 4 tests: HBsAg, IgM anti-HBc, and antibodies to HAV and HCV
  • HBV persists in the body of all patients with infection, even those with evidence of serological recovery (e.g. a patient with positive anti-HBs and positive total anti-HBc.) This explains why anyone with a history of HBV infection who receives immunosuppressive therapy is at risk for HBV reactivation and a flare of HBV disease. 

How should we think about seroconversion?

Source: UpToDate

Early in an infection, unbound antigen exceeds the amount of bound antibodies. After seroconversion, antibodies exceed antigen, so there is a detectable amount of free antibody while all the antigen is bound and undetectable.

Seroconversion makes it unusual to see positive HBsAg and positive anti-HBs at the same time (or positive HBeAg with positive anti-HBe at the same time.)

How would you interpret the following HBV serology results?

Case 1

  • negative HBsAg
  • negative total anti-HBc
  • negative anti-HBs

Case 2

  • negative HBsAg
  • negative total anti-HBc
  • positive anti-HBs

Case 3

  • negative HBsAg
  • positive total anti-HBc
  • positive anti-HBs

Case 4

  • positive HBsAg
  • positive total anti-HBc
  • positive IgM anti-HBc
  • negative anti-HBs

Case 5

  • positive HBsAg
  • positive total anti-HBc
  • negative IgM anti-HBc
  • negative anti-HBs

Want to know more? Check out CDC’s great videos on hepatitis serologies!

Who should be screened for HBV? 

  • People born in countries with HBV prevalence ≥2%
  • People born in the US not vaccinated as infants whose parents were born in regions with high rates of HBV infection (i.e. regions with HBsAg prevalence ≥8%)
  • Men who have sex with men
  • People who inject drugs
  • People with HIV
  • Household and sexual contacts of HBV-infected people
  • People requiring immunosuppressive therapy
  • People with ESRD, including anyone on dialysis
  • Blood and tissue donors
  • People with elevated ALT levels (>19 IU/L for women and >30 IU/L for men)
  • Pregnant women (recommended screening with HBsAg only)
  • Infants born to HBV-infected mothers (recommended screening with HBsAg and anti-HBs) 

Who should receive the HBV vaccine?

  • All unvaccinated children <19yo
  • Sex partners of HBsAg-positive people
  • Sexually active people who are not in long-term, mutually monogamous relationships
  • People seeking evaluation or treatment for an STI
  • Men who have sex with men
  • People who inject drugs
  • Household contacts of HBsAg-positive people
  • Residents/staff of facilities for developmentally disabled patients
  • Healthcare and public safety workers with reasonably anticipated risk for exposure to blood or blood-contaminated body fluids
  • People with ESRD, including anyone on dialysis
  • International travelers to regions with intermediate or high levels of HBV infection
  • People with chronic liver disease (e.g. cirrhosis, fatty liver disease, alcoholic liver disease, autoimmune hepatitis, and ALT or AST level >2x ULN)
  • People with HCV infection or HIV infection
  • Unvaccinated adults with diabetes mellitus aged 19-59yo (at the clinician’s discretion if ≥60yo)
  • Incarcerated persons
  • All other people who wish to be vaccinated
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