Hepatitis Serologies — Bone Wizardry

⚡ Opening Challenge — Don't scroll past this

A patient has fatigue and jaundice. Labs come back:

HBsAg	NEGATIVE
anti-HBs	NEGATIVE
anti-HBc IgM	POSITIVE
anti-HBc IgG	NEGATIVE

HBsAg is negative. anti-HBs is negative. Is this patient infected, immune, or what?

This is the Window Period. The most-tested HBV trap on boards.

HBsAg disappeared — the body cleared surface antigen. But anti-HBs hasn't formed yet. The only positive marker is anti-HBc IgM, which signals acute infection. The window is open.

If you didn't know that, you might think: "Both HBsAg and anti-HBs are negative... maybe uninfected?" That's exactly the trap. The IgM anti-core is the only clue. Know it cold.

Marker Key

What Each Marker Actually Means

Hover any term for the mechanism. The markers have personalities — learn them.

HBsAg — Surface Antigen

The viral surface coat protein, actively shed into blood. Present = actively infected. Appears first (1–10 weeks post-exposure), disappears by ~6 months in acute infection. If it's still positive at 6 months → chronic.

Memory: Surface Antigen = Still infected. Both start with S.

anti-HBs — Antibody to Surface Antigen

Protective neutralizing antibody. Positive = immune. Appears after HBsAg clears (or after vaccination). This is the only marker the vaccine generates.

Memory: anti-HBs = Safe. Surface antibody = shield = you're good.

anti-HBc IgM — IgM Core Antibody

ACUTE infection marker. IgM = immediate/early immune response. Appears ~1 month post-exposure. The only positive marker during the window period — this is why it's high yield. Goes away in ~6 months as IgG takes over.

anti-HBc IgG — IgG Core Antibody

Chronic marker / "been there". Indicates past or ongoing infection. Persists for life after any HBV exposure. NOT produced by the vaccine — this is how you tell "recovered from infection" vs "vaccinated."

HBeAg — e Antigen

Secreted viral core protein that reflects active viral replication. High HBeAg = high viral load = high infectivity. Seroconversion (HBeAg → anti-HBe) marks viral control in chronic infection. Loss of HBeAg with treatment = good sign.

The Core

The 5 HBV Serology Scenarios

Tap any card to see the full panel. These are the 5 patterns boards test.

Acute Infection

Symptomatic, within first 6 months

Marker	Result	Why
HBsAg	+	Virus is present, surface coat being shed
anti-HBc IgM	+	Acute = IgM. Always positive in acute HBV.
anti-HBs	−	Can't have HBsAg and anti-HBs at same time
HBeAg	+	Active replication = high infectivity
anti-HBc IgG	−	IgG takes months to develop

Board pearl: HBsAg + anti-HBc IgM together = acute HBV. Don't need anything else.

Most adults clear acute HBV spontaneously (95%). Progression to chronic is higher in neonates (90%) and immunocompromised.

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Window Period

The board trap. Know this cold.

⚠ Most-Tested Board Trap

HBsAg has cleared. anti-HBs hasn't formed yet. If you only look at those two, this patient looks uninfected. That's the trap.

Marker	Result	Why
HBsAg	−	Antigen cleared — immune system won
anti-HBs	−	Not formed yet — immune system is catching up
anti-HBc IgM	+	The ONLY clue. This is what saves you.
anti-HBc IgG	−	IgG hasn't kicked in yet

Anti-HBc IgM alone = window period. Patient is still infected but in a serological gap.

The window lasts weeks to months. These patients are still infectious. Don't clear them for blood donation.

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Recovered / Immune (Prior Infection)

Cleared the virus, has lifelong markers

Marker	Result	Why
HBsAg	−	Virus cleared
anti-HBs	+	Protective antibody formed after clearance
anti-HBc IgM	−	IgM fades — acute phase is over
anti-HBc IgG	+	Marker of prior exposure. Persists forever.

anti-HBs + anti-HBc IgG = recovered from natural infection. This pattern distinguishes from vaccination.

These patients have lifelong immunity and do not need vaccination. anti-HBc IgG is the fingerprint that says "I was actually infected."

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Vaccinated / Immune (No Prior Infection)

Only one marker is positive

Marker	Result	Why
HBsAg	−	Never infected
anti-HBs	+	Vaccine generates anti-HBs ONLY
anti-HBc IgM	−	Never infected = no core antibody
anti-HBc IgG	−	Never infected = no core antibody
HBeAg	−	Never infected

anti-HBs ALONE = vaccinated. No anti-HBc IgG. That's the entire key to separating vaccinated from recovered.

The HBV vaccine is a recombinant surface antigen vaccine — it only teaches the immune system to recognize HBsAg. So anti-HBs is the only antibody produced.

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Chronic Active Infection

HBsAg positive >6 months

Marker	Result	Why
HBsAg	+	Still present >6 months = chronic by definition
anti-HBs	−	Can't coexist with HBsAg
anti-HBc IgM	−	IgM is acute — faded after 6 months
anti-HBc IgG	+	Chronic = ongoing exposure = IgG persists
HBeAg	±	Positive = actively replicating (high infectivity)

HBsAg + anti-HBc IgG (no IgM, no anti-HBs) = chronic HBV. The absence of IgM confirms it's not acute.

HBeAg+ in chronic = high viral load, high infectivity. HBeAg− in chronic = "inactive carrier" — lower viral load but still HBsAg+.

Chronic HBV → risk for cirrhosis + hepatocellular carcinoma. Annual ultrasound + AFP surveillance.

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Memory Hooks

Tap to Reveal

Max 2. These are designed to stick.

🔑

How do I remember HBsAg vs anti-HBs?

S = S rule.
Surface Antigen = Still infected.
anti-HBs = Safe.

Antigen present? Still sick. Antibody to surface? You're protected. The letters tell you.

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🔑

Vaccinated vs Recovered — how do I tell them apart when both have anti-HBs+?

Core = was actually there.
Vaccine never touches the core. No HBcAg in the vaccine = no anti-HBc ever.

So: anti-HBs alone = vaccinated.
anti-HBs + anti-HBc IgG = recovered.

If they have a core antibody, the virus was inside them. Period.

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Visual Reference

HBV Infection Timeline

When markers appear and disappear over a typical acute→recovery course.

Window period = HBsAg cleared, anti-HBs not yet formed → anti-HBc IgM is the only positive

Elimination Game

Match the Panel

See a serology result. Eliminate scenarios. Name the diagnosis. This is how it works on test day.

Score: 0 / 0

Quick Reference

The Hepatitis Alphabet

HAV, HBV, HCV, HDV, HEV — what makes each one different.

Virus	Nucleic Acid	Transmission	Chronic?	High Yield Fact
HAV	RNA	Fecal-oral Contaminated food/water. Shellfish (filter feeders concentrate virus). Daycare outbreaks, travel to endemic areas.	No — always self-limited	anti-HAV IgM = acute. anti-HAV IgG = immune. No carrier state.
HBV	DNA	Blood/sexual/perinatal	Yes — 5–10% adults, 90% neonates	5 serology scenarios. Window period. Vaccine = anti-HBs only. DNA virus (only hepatitis DNA virus you need to know).
HCV	RNA	Blood-borne (IVDU, transfusion pre-1992)	Yes — 75–85% go chronic	Most common chronic blood-borne infection in USA. No vaccine. Tx: direct-acting antivirals (sofosbuvir). anti-HCV = exposed (not protective — test for RNA to confirm active).
HDV	RNA	Blood/sexual (needs HBV co-infection)	Yes if co-infect	Delta virus — defective HDV is an incomplete virus. It REQUIRES HBsAg as its envelope to replicate. No HBV = no HDV. HBV vaccination prevents HDV co-infection. . Two patterns: co-infection (HBV+HDV together, usually clears) vs superinfection (HDV on chronic HBV → fulminant).
HEV	RNA	Fecal-oral Endemic in Southeast Asia, Central America, Africa. Major outbreaks from contaminated water. Pigs are a reservoir.	No — self-limited (except pregnancy)	Catastrophic in pregnancy — 20% mortality in 3rd trimester. "Pregnant woman returns from India with liver failure" = HEV until proven otherwise. Like HAV but deadlier in pregnancy.

RNA vs DNA — just one to know

HBV is the only DNA hepatitis virus in this list. HAV, HCV, HDV, HEV are all RNA. Don't overcomplicate it — boards just want you to know HBV = DNA.

Fecal-oral group: HAV and HEV — both RNA, both self-limited (mostly), both via contaminated water/food. The difference: HEV kills pregnant women. HAV doesn't.

Blood-borne chronic group: HBV and HCV — both go chronic, both can cause cirrhosis + HCC. HCV more often goes chronic. HBV has a vaccine; HCV doesn't.

Practice

Clinical Vignette Quiz

4 questions, randomized each load. Shuffle answer order. Confetti on correct.