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Hepatitis B, C and D serology

16 min

  • Read HBsAg, anti-HBs, and anti-HBc together to classify hepatitis B status
  • Choose RNA follow-up to determine current hepatitis C infection
  • Distinguish HDV exposure from current infection in a person with HBV
  • Apply each infection's own IgM and paired-titer timing rules to a serology result

Read the full reference

Try first

Try first

An adult's first hepatitis B panel shows HBsAg nonreactive, total anti-HBc reactive and anti-HBs reactive. What does the panel show?

The next section explains it.

The next section explains it.

Right. The next section explains why.

The next section explains it.

The next section explains it.

Get the idea

Hepatitis B takes three markers read together

CDC recommends HBsAg, anti-HBs and total anti-HBc as the first panel for an adult never screened before.1 Each marker answers one question.

  • HBsAg shows current infection.
  • Total anti-HBc shows natural infection, current or past. Vaccination never produces it.
  • Anti-HBs shows immunity, from recovery or from vaccination. Above 10 mIU/mL after a completed vaccine series, it is evidence of immunity.
  • IgM anti-HBc marks recent infection, usually within 6 months.1
HBsAgTotal anti-HBcAnti-HBsReading
NonreactiveNonreactiveNonreactiveSusceptible
NonreactiveNonreactiveReactiveImmune after vaccination
NonreactiveReactiveReactiveResolved natural infection
ReactiveReactiveNonreactiveCurrent infection, with IgM anti-HBc separating acute from chronic

1

Hepatitis C is settled by RNA

Testing starts with anti-HCV, and a reactive result reflexes to an HCV RNA nucleic acid amplification test (NAAT). Anti-HCV usually persists after the infection clears or is treated. Detected RNA shows current infection. A reactive antibody with RNA not detected usually means no current infection.2

Hepatitis D is settled by RNA too

Hepatitis D virus (HDV) needs HBsAg to form new virus, so it is tested in a person with hepatitis B. Total anti-HDV shows exposure. HDV RNA shows current infection, and WHO supports reflexing a reactive antibody to RNA.3 IgM anti-HDV can be late, brief or present in chronic infection, so it cannot show viremia alone.4

Each marker keeps its own clock

A marker reads correctly only against the date of exposure or symptoms. HBsAg appears several weeks after exposure. During the hepatitis B window period, HBsAg has cleared and anti-HBs has not yet formed, so IgM anti-HBc is the one marker of recent infection.1 Anti-HCV usually appears 8 to 11 weeks after exposure, and HCV RNA appears earlier. After a recent exposure, a nonreactive antibody leaves infection open, and RNA can answer sooner.2 These rules belong to each virus. Epstein-Barr virus, for example, is dated from its IgM and nuclear antigen antibodies, and paired sera add little because its antibodies appear near onset.5 Apply the timing rule of the infection in front of you.

References
  1. Centers for Disease Control and Prevention. Clinical testing and diagnosis for hepatitis B. Updated August 14, 2026. Accessed September 27, 2026. https://www.cdc.gov/hepatitis-b/hcp/diagnosis-testing/index.html
  2. Centers for Disease Control and Prevention. Clinical screening and diagnosis for hepatitis C. January 31, 2025. Accessed September 27, 2026. https://www.cdc.gov/hepatitis-c/hcp/diagnosis-testing/index.html
  3. World Health Organization. Guidelines for the Prevention, Diagnosis, Care and Treatment for People With Chronic Hepatitis B Infection. World Health Organization; 2024. Accessed September 27, 2026. https://www.who.int/publications/i/item/9789240090903
  4. Centers for Disease Control and Prevention. Hepatitis D virus 2025 case definition. Accessed September 27, 2026. https://ndc.services.cdc.gov/case-definitions/hepatitis-d-virus-hdv/
  5. Centers for Disease Control and Prevention. Laboratory testing for Epstein-Barr virus. April 10, 2024. Accessed September 27, 2026. https://www.cdc.gov/epstein-barr/php/laboratories/index.html

Watch one

A 34-year-old man has had dark urine and jaundice for 3 weeks. His hepatitis B panel reads:

What stage of hepatitis B does the panel show?

TestResultPreviousReference intervalFlag
HBsAgNonreactiveNonreactive
Total anti-HBcReactiveNonreactive
IgM anti-HBcReactiveNonreactive
Anti-HBsNonreactive

Specimen: H 3, L 12, I 18. Serum

  1. HBsAg is nonreactive. No surface antigen is detected today.

    HBsAg answers whether infection is current, so it is read first.

  2. Total anti-HBc is reactive, so this is natural infection. Vaccination alone would leave it nonreactive.

    Total anti-HBc shows whether the person ever met the virus.

  3. Anti-HBs is nonreactive, so recovery is not complete.

    Anti-HBs shows whether recovery has produced immunity.

  4. IgM anti-HBc is reactive, which marks infection within about 6 months.

    With HBsAg gone and anti-HBs absent, only the IgM class can date the infection.

  5. Three weeks of jaundice fits a recent infection that is clearing.

    The pattern has to fit the history before it is released.

The window period of a recent hepatitis B infection. HBsAg has cleared, anti-HBs has not yet formed, and IgM anti-HBc is the marker that shows it.

Your turn

Problem 1 of 3

HBsAg and total anti-HBc are nonreactive, and anti-HBs is reactive in a person with documented completed hepatitis B vaccination. Which pattern does this support?

Correct. Vaccination produces anti-HBs without anti-HBc, which forms only after exposure to core antigen during natural infection. A concentration of 10 mIU/mL or higher after a completed series is evidence of immunity.

Incorrect. Resolved natural infection has reactive total anti-HBc together with anti-HBs.

Incorrect. In the window, HBsAg has cleared, anti-HBs has not yet appeared, and total anti-HBc, including IgM anti-HBc, is reactive.

Hint
  1. Ask which of the three markers a vaccine can produce.
  2. The vaccine contains surface antigen only. Look at which core marker is missing.

Review Hepatitis B

Problem 2 of 3

A reactive anti-HCV result needs assessment for current infection. Which test supplies the next direct evidence?

Incorrect. A second reactive antibody result still cannot separate current from resolved infection, because anti-HCV persists after clearance or treatment.

Correct. Detected HCV RNA shows current infection. A reactive antibody with RNA not detected usually means no current infection, with repeat RNA when recent exposure or specimen concerns remain.

Incorrect. Alanine aminotransferase (ALT) reflects liver injury from any cause. It does not detect HCV or show whether infection is current.

Hint
  1. Anti-HCV stays after the virus is gone.
  2. Ask which option looks for something other than antibody.

Review Hepatitis D and C

Problem 3 of 3

A woman with chronic hepatitis B, HBsAg reactive, has a reactive total anti-HDV. What does the laboratory report this result as showing, and what follows?

Total anti-HDV shows exposure. It stays reactive after the virus is gone, so it cannot show that HDV is present now.

Read a reactive anti-HDV as current HDV infection

Total anti-HDV shows exposure, and IgM anti-HDV can be delayed, brief, or present in chronic infection. Reporting current infection from antibody skips the HDV RNA test that establishes viremia.

A reactive total antibody already shows exposure. IgM anti-HDV cannot settle current infection either.

The antibody cannot date the exposure. Superinfection of a person with chronic hepatitis B often stays chronic.

Total anti-HDV shows she has met HDV. Detected HDV RNA would show current infection.

Review Hepatitis D and C

Use it

  • Marisol Ferreira, 29, is a nurse. She had a needlestick from a patient of unknown status 5 weeks ago.
  • She completed a hepatitis B vaccine series 6 years ago, and the record is in her file.
  • Her results today:
TestResultPreviousReference intervalFlag
Anti-HCVNonreactiveNonreactive
HBsAgNonreactiveNonreactive
Total anti-HBcNonreactiveNonreactive
Anti-HBs86 mIU/mL

Specimen: H 2, L 10, I 1. Serum, collected 5 weeks after the needlestick

Decision 1 of 3

What does the nonreactive anti-HCV show 5 weeks after the needlestick?

Anti-HCV usually appears 8 to 11 weeks after exposure. At 5 weeks a nonreactive antibody cannot exclude infection.

A fourfold rise in paired sera is a rule for other infections. HCV timing turns on when antibody and RNA appear.

Applied one paired-titer rule to every infection

Marker timing differs by infection: Lyme testing disregards an IgM blot after 30 days of illness, EBV relies on VCA IgM with absent EBNA antibody, and paired EBV sera add little because antibodies appear near onset. Applying one fourfold-rise or IgM rule everywhere misreads timing for infections that do not follow it.

Antibody usually forms 8 to 11 weeks after exposure. RNA appears earlier and can answer sooner.

Review Reading viral markers

Decision 2 of 3

The occupational health clinician asks which test would show HCV infection soonest. Which do you suggest?

HCV RNA appears before antibody. A recent exposure is a reason to test RNA after a nonreactive antibody.

Alanine aminotransferase (ALT) rises with liver injury from any cause. It does not detect HCV.

One week later is still inside the usual 8 to 11 weeks before antibody appears.

Review Hepatitis D and C

Decision 3 of 3

How does her hepatitis B panel read?

Anti-HBs is above 10 mIU/mL after a documented series, with HBsAg and total anti-HBc nonreactive.

Natural infection leaves total anti-HBc reactive. Hers is nonreactive, and the anti-HBs came from the vaccine.

Called anti-HBs alone evidence of natural infection

Vaccination produces anti-HBs without anti-HBc. Natural infection leaves total anti-HBc, usually for life. Reading anti-HBs alone as past infection mislabels a vaccine response and misstates reactivation risk.

A susceptible person has no anti-HBs. Her 86 mIU/mL shows immunity.

Review Hepatitis B

The clue that settled the HCV question is the date of the needlestick. At 5 weeks antibody is often still absent, so the nonreactive anti-HCV cannot be read as no infection, and HCV RNA answers sooner.

Keep

Sources checked