Skip to content

Add your earlier progress to your account?

From before you signed in, this browser has:

Which plan do you want to keep?

You answered the plan questions before you signed in, and those answers don't match the plan saved on your account.

SettingSaved planNew answers

Study progress is waiting to be saved

Hepatitis B, C and D serology

16 min

Skills you'll build4 skills
  • 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

At the bench: Relate viral serology findings to the stage of infection

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?

Keep going to see the reasoning.

Keep going to see the reasoning.

Right. Keep going to follow the reasoning.

Keep going to see the reasoning.

Keep going to see the reasoning.

Get the idea

Use the explanation to check your first decision.

The hepatitis B panel

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

  • 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-HBsInterpretation
NonreactiveNonreactiveNonreactiveSusceptible
NonreactiveNonreactiveReactiveImmune after vaccination
NonreactiveReactiveReactiveResolved natural infection
ReactiveReactiveNonreactiveCurrent infection, with IgM anti-HBc separating acute from chronic
NonreactiveReactiveNonreactiveIsolated anti-HBc, with more than one explanation

1

The isolated anti-HBc pattern cannot be interpreted from these three markers alone. It fits a resolved infection with waned anti-HBs, an occult infection, a false-reactive anti-HBc, the window period of a recent infection, an HBsAg variant the assay misses, or passive antibody in an infant. Recent results, the history and HBV DNA distinguish them.1,5

Hepatitis C RNA testing

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 testing

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 is not a reliable marker of viremia.4

Timing of markers

Each marker is interpreted with the date of exposure or symptom onset. 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 does not exclude infection, and RNA can detect it sooner.2

Follow the bench demonstration

Sources for this step
References
  1. Centers for Disease Control and Prevention. Clinical testing and diagnosis for hepatitis B. Updated August 14, 2026. Accessed October 2, 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. Interpretation and differentiation of isolated positive hepatitis B core antibody. July 2025. Accessed October 2, 2026. https://www.cdc.gov/hepatitis-b/media/pdfs/2025/08/FINAL-7.25.25-interpretation-differentiation-isolated-positive-hepatitis-b-core-antibody.pdf

Watch one

Read each decision and its explanation.

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?

TestResultReference intervalFlag
HBsAgNonreactiveNonreactiveNonreactive
Total anti-HBcReactiveNonreactiveNonreactive
IgM anti-HBcReactiveNonreactiveNonreactive
Anti-HBsNonreactive

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

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

    HBsAg shows 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 was ever infected.

  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 cleared 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 is checked against the history before release.

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.

Practice this skill

Your turn

Problem 1 of 3 · Hints available

A 52-year-old man's first hepatitis B panel reads HBsAg nonreactive, total anti-HBc reactive and anti-HBs nonreactive. He has no earlier hepatitis B results on file. Your laboratory's procedure says:

  • HBsAg reactive: report the panel and add IgM anti-HBc.
  • Total anti-HBc and anti-HBs both reactive: report "Resolved infection".
  • Total anti-HBc reactive alone, with no hepatitis B results in the past 6 months: report the results with the comment "Isolated anti-HBc. Further testing needed." Call the ordering provider to offer IgM anti-HBc and HBV DNA on this specimen.

What do you do?

Resolved infection requires a reactive anti-HBs, and his is nonreactive. A reactive anti-HBc alone fits several explanations, including occult infection and the window period.

Reported an isolated anti-HBc as resolved infection

Resolved infection needs anti-HBs as well as total anti-HBc. A reactive anti-HBc alone also fits occult infection, the window period and a false-reactive result, so the laboratory reports the pattern as unresolved and offers HBV DNA and IgM anti-HBc.

Only total anti-HBc is reactive and he has no recent results, so the line for anti-HBc alone applies. IgM anti-HBc and HBV DNA distinguish a recent or occult infection from a resolved or false-reactive result.

A false-reactive anti-HBc is one possible explanation. HBV DNA and the history resolve it, and the procedure releases no interpretation before then.

A repeat HBsAg does not rule out occult infection or an HBsAg variant. The procedure reports these results and offers HBV DNA and IgM anti-HBc on this specimen.

Hint
  1. Name the pattern first. Which of the three markers are reactive?
  2. Anti-HBs is nonreactive, so the line for resolved infection does not fit. Read the line for anti-HBc reactive alone.

Review Hepatitis B

Problem 2 of 3 · Hints available

A reactive anti-HCV result needs assessment for current infection. Which test is performed next to detect current infection?

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 persists after the virus is cleared.
  2. Ask which option looks for something other than antibody.

Review Hepatitis D and C

Problem 3 of 3 · On your own

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 cleared, 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 confirm current infection either.

The antibody cannot date the exposure. HDV superinfection in a person with chronic hepatitis B often becomes chronic.

Total anti-HDV shows exposure to HDV. Detected HDV RNA would show current infection.

Review Hepatitis D and C

Use it

Read the case evidence, then make each decision. The step is complete without it.

  • Marisol Faber, 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:
TestResultReference intervalFlag
Anti-HCVNonreactiveNonreactiveNonreactive
HBsAgNonreactiveNonreactiveNonreactive
Total anti-HBcNonreactiveNonreactiveNonreactive
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.

HCV testing after exposure depends on when antibody and RNA appear. Paired sera with a fourfold rise are not used.

Antibody usually forms 8 to 11 weeks after exposure. RNA appears earlier and can be detected 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 is her hepatitis B panel interpreted?

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 HCV result depends on the date of the needlestick. At 5 weeks antibody is often absent, so the nonreactive anti-HCV does not exclude infection. HCV RNA can be detected sooner.

For reference

Sources checked