Hepatitis Serologies

Give every marker one job

Start with exposure and current infection; replication markers come second.

HBsAg is viral surface antigen in blood and usually means current infection, acute or chronic; a transient positive result can occur soon after vaccination.

Anti-HBs is antibody to surface antigen and indicates immunity after recovery or successful vaccination, but it does not reveal how immunity was acquired without anti-HBc.

Total anti-HBc combines IgM and IgG-class core antibody and marks prior or current natural exposure; vaccination alone never creates anti-HBc.

IgM anti-HBc supports recent acute infection, usually within six months, but can reappear during a severe chronic flare or reactivation.

HAV uses IgM anti-HAV for acute infection. HCV antibody marks exposure and requires HCV RNA to establish current infection. HDV can infect only in the presence of HBV surface antigen.

Surface asks current infection or immunity; core asks natural exposure.

Build the classic HBV patterns

Read the same four tests in the same order every time.

Acute HBV usually has HBsAg positive, total anti-HBc positive, IgM anti-HBc positive, and anti-HBs negative.

During the window period, HBsAg has disappeared before anti-HBs is detectable; IgM anti-HBc remains the decisive positive marker.

Chronic HBV has persistent HBsAg and total anti-HBc with negative IgM anti-HBc and negative anti-HBs.

Resolved natural infection has negative HBsAg, positive total anti-HBc, and positive anti-HBs, while vaccine immunity has negative HBsAg, negative total anti-HBc, and positive anti-HBs.

In the window, the surface goes quiet and the core tells the story.

Thresholds that change classification or prevention

These values are decision points, not trivia.

HBsAg persistence for at least 6 months supports chronic HBV rather than acute infection.

Anti-HBs of at least 10 mIU/mL after a completed vaccine series is the conventional protective response threshold in settings where post-vaccination testing is indicated.

In pregnancy, HBV DNA greater than 200,000 IU/mL identifies high transmission risk and supports maternal tenofovir therapy in the third trimester in addition to newborn prophylaxis.

The 2026 AASLD-IDSA guideline recommends starting tenofovir disoproxil fumarate or tenofovir alafenamide at gestational week 28 for pregnancy with HBV DNA above the transmission threshold.

Six months classifies chronic infection; 200,000 DNA changes pregnancy management.

Replication is not the same as exposure

Once infection status is known, ask how actively the virus is replicating.

HBeAg generally tracks active replication and higher infectivity, while anti-HBe often follows seroconversion to lower replication.

HBeAg-negative disease can still replicate because precore or basal core promoter variants reduce e-antigen expression; never use anti-HBe as proof that HBV DNA is suppressed.

HBV DNA is the direct measure of circulating viral replication and is used for staging, treatment decisions, response monitoring, pregnancy transmission risk, and suspected occult infection.

Occult HBV means HBsAg is negative while HBV DNA is detectable. Reactivation is a loss of immune control with a rise or reappearance of HBV DNA, sometimes followed by HBsAg seroreversion and hepatitis flare.

Antibodies tell history; DNA tells what the virus is doing now.

Map antigen, antibody, and genome

The marker name becomes easier when its physical source is explicit.

HBsAg is the envelope protein displayed on virions and excess subviral particles; anti-HBs binds that surface target and can neutralize entry.

HBcAg remains inside infected hepatocytes and virions rather than circulating as a routine serum antigen; the immune system leaves total and IgM anti-HBc in blood as evidence of exposure.

HBeAg is a secreted protein related to the core gene region and serves as an imperfect serum proxy for replication.

HBV covalently closed circular DNA persists in hepatocyte nuclei after apparent clinical resolution, which explains why immunosuppression can permit reactivation.

HDV borrows the HBV surface envelope, so HBV vaccination prevents acquisition of both HBV and dependent HDV infection.

Core antibody is in the blood because core antigen is not the routine serum marker.

Screen before the stakes rise

Pregnancy and immunosuppression convert a quiet serology pattern into a prevention decision.

For first-time adult HBV screening, use the triple panel: HBsAg, anti-HBs, and total anti-HBc. Add IgM anti-HBc when acute infection is suspected.

Screen every pregnancy for HBsAg early regardless of vaccination or prior testing. If HBsAg is positive, obtain HBV DNA because high viremia changes maternal antiviral planning and newborn prophylaxis.

Before chemotherapy, B-cell-depleting therapy, transplantation, or substantial immunosuppression, assess HBsAg and total anti-HBc, usually with anti-HBs, because both chronic and resolved infection can reactivate.

An isolated total anti-HBc result can reflect resolved infection with waned anti-HBs, occult infection, window-period acute infection, a false-positive test, passive infant antibody, or an HBsAg mutant. Context, IgM anti-HBc, repeat testing, and HBV DNA resolve the branch.

For HCV, a reactive antibody must reflex to HCV RNA. For HAV, IgM anti-HAV diagnoses acute infection. For HDV, test only in a person with current HBV infection or relevant risk because HDV requires HBsAg.

The test panel stays simple; the context decides what a positive core antibody means.