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PA24.{1,6} | Bilirubin Metabolism, Jaundice & LFT Interpretation — SDL Guide (Part 4)

Viral Hepatitis Serology: Hepatitis B Window Periods

Three-panel diagram showing the serological timeline of acute Hepatitis B infection with the window period highlighted, a marker interpretation table, and a clinical diagnostic flowchart for the window period. — **Panel A:** HBsAg curve (red), Anti-HBc IgM curve (orange), Anti-HBc IgG curve (blue), Anti-HBs curve (green), Window Period shaded band (yellow), symptom onset arrow, week-axis tick marks 0–72. **Panel B:** Six-row serological pattern table: columns = HBsAg / Anti-HBs / Anti-HBc IgM / Anti-HBc IgG / Interpretation; rows cover acute early, window period, resolved, vaccinated, chronic, and susceptible states. **Panel C:** Clinical decision flowchart: HBsAg-neg/Anti-HBs-neg patient → Anti-HBc IgM test → IgM positive (window period acute HBV) or IgM negative (other cause); 'Clinical Pearl' note on window period duration.

Hepatitis B serology interpretation is a high-yield clinical skill with direct implications for diagnosis, treatment decisions, and post-exposure management. The key markers are:

Marker	What it is	What elevation means
HBsAg	Surface antigen (envelope protein)	Active infection (acute or chronic) — appears 1–10 wks after exposure, before symptoms
Anti-HBs (HBsAb)	Antibody to surface antigen	Recovery/immunity — appears after HBsAg clears; also positive after vaccination
Anti-HBc IgM	IgM antibody to core antigen	Acute infection (window period marker — positive when HBsAg has cleared but anti-HBs not yet appeared)
Anti-HBc IgG (total anti-HBc)	IgG antibody to core antigen	Past exposure (recovered or chronic); NOT induced by vaccine
HBeAg	e-antigen (secreted core protein)	High viral replication, high infectivity
Anti-HBe	Antibody to e-antigen	Declining replication — seroconversion is a treatment goal in HBeAg-positive chronic hepatitis B

Interpretation patterns:

Pattern	HBsAg	Anti-HBs	Anti-HBc IgM	Anti-HBc IgG	HBeAg	Interpretation
Acute hepatitis B	+	−	+	−	+/−	Active acute infection
Window period	−	−	+	+/−	−	HBsAg cleared, anti-HBs not yet; anti-HBc IgM is the only positive marker
Resolved infection	−	+	−	+	−	Recovered; immune via natural infection
Vaccinated	−	+	−	−	−	Immune via vaccine (no core antibody — vaccine contains only HBsAg)
Chronic HBV (active)	+	−	−	+	+	>6 months HBsAg positive; high replication
Chronic HBV (inactive)	+	−	−	+	−	Carrier state; lower replication

Hepatitis C serology:
- Anti-HCV (ELISA): screener — positive in active and resolved infection. Cannot distinguish.
- HCV RNA (PCR): confirms active replication; positive within days of infection (before antibody). A positive anti-HCV + undetectable HCV RNA = resolved infection.

Two-panel diagram: Panel A shows a Hepatitis B serology timeline graph with seven color-coded curves (HBsAg, HBeAg, ALT, anti-HBc IgM, anti-HBc IgG, anti-HBe, anti-HBs) plotted against weeks after exposure with clinical phase brackets (incubation, acute, window, recovery, immunity) and the window period demarcated by dashed vertical lines; Panel B shows a serology interpretation reference table listing marker positivity patterns for each clinical phase including a vaccination row highlighted to distinguish vaccine-induced from natural immunity. — **Panel A:** Seven labeled curves: HBsAg (red), HBeAg (orange), ALT/Symptoms (teal), anti-HBc IgM (magenta), anti-HBc IgG Total (navy), anti-HBe (green), anti-HBs/Protective level (gold); phase brackets: Incubation, Acute Hepatitis, Window Period, Recovery, Immunity; dashed vertical lines bounding the window period. **Panel B:** Serology interpretation table — rows: Incubation, Acute Hepatitis, Window Period (highlighted orange), Recovery, Resolved Infection, Chronic HBV, Vaccination (highlighted blue); columns: HBsAg, HBeAg, anti-HBc IgM, anti-HBc IgG, anti-HBe, anti-HBs; footnote distinguishing vaccination (anti-HBc negative) from resolved natural infection (anti-HBc positive).

SELF-CHECK

A 28-year-old healthcare worker has a needlestick injury. Baseline serology: HBsAg negative, anti-HBs 150 mIU/mL, anti-HBc IgM negative, anti-HBc IgG negative. What is the correct interpretation?

A. Chronic hepatitis B carrier state

B. Window period of acute hepatitis B infection

C. Resolved natural hepatitis B infection

D. Protective immunity from prior vaccination

Reveal Answer

Answer: D. Protective immunity from prior vaccination

Anti-HBs positive (>10 mIU/mL is protective), HBsAg negative, and — crucially — anti-HBc IgG negative. Anti-HBc is generated only by natural infection, not by vaccination (the vaccine contains only HBsAg). Therefore a pattern of anti-HBs positive + anti-HBc negative = vaccination-induced immunity. Resolved natural infection would show anti-HBs + anti-HBc IgG both positive. Window period shows anti-HBc IgM positive. Chronic HBV shows HBsAg positive.

Clinical Integration: Putting It All Together

Four-panel clinical decision algorithm showing the three-step LFT framework: Step 1 pattern recognition (hepatocellular, cholestatic, prehepatic), Step 2 severity markers, Step 3 aetiology narrowing table, and a clinical case resolution demonstrating obstructive jaundice from carcinoma head of pancreas. — **Panel A:** Step 1 — Pattern Recognition: three color-coded columns for Hepatocellular (ALT/AST markedly elevated, ALP mildly elevated), Cholestatic (ALP/GGT markedly elevated, transaminases mildly elevated), and Prehepatic (indirect bilirubin elevated, normal enzymes). **Panel B:** Step 2 — Severity & Acuity ladder: PT prolonged + albumin falling (impaired synthesis), ALT >40× normal (acute/severe hepatocellular injury), ALP >4× + GGT elevated + jaundice (significant cholestasis). **Panel C:** Step 3 — Aetiology Narrowing table: five pattern–diagnosis pairs covering viral hepatitis serology, alcoholic liver disease (AST:ALT >2:1), choledocholithiasis, carcinoma head of pancreas, and primary biliary cholangitis. **Panel D:** Case Resolution: specimen-report box with Direct bilirubin 7.8/9.2 (84% conjugated), ALP 480, GGT 310, minimal transaminase rise, urine bilirubin positive, urobilinogen absent → Posthepatic/Obstructive Pattern; clinical note: Courvoisier sign + painless jaundice → carcinoma head of pancreas → Ultrasound next.

The three-step LFT framework in practice:

Step 1 — Dominant pattern?
- Transaminases (ALT/AST) markedly elevated, ALP mildly elevated → Hepatocellular
- ALP/GGT markedly elevated, transaminases mildly elevated → Cholestatic
- Bilirubin predominantly indirect, transaminases/ALP normal → Prehepatic

Step 2 — Severity and acuity?
- PT prolonged + albumin falling → impaired synthesis → severity marker (indicates significant parenchymal reserve loss)
- ALT >40× normal → acute/severe hepatocellular injury (paracetamol, ischaemia, fulminant viral)
- ALP >4× + GGT elevated + jaundice → significant cholestasis

Step 3 — Aetiology narrowing:
- Hepatocellular + viral prodrome → hepatitis serology (HBsAg, anti-HBc IgM, anti-HCV)
- Hepatocellular + history of alcohol → AST:ALT >2:1, ↑GGT, ↓MCV
- Cholestatic + pain + fever → choledocholithiasis (ultrasound)
- Cholestatic + painless + weight loss → carcinoma head of pancreas (CECT)
- Cholestatic + AMA positive + middle-aged woman → Primary biliary cholangitis

Return to the opening case: Direct bilirubin 7.8/total 9.2 (84% conjugated), ALP 480, GGT 310, transaminases minimally elevated, urine bilirubin positive, urobilinogen absent → Posthepatic/obstructive pattern. Courvoisier sign in a 35-year-old man with painless progressive jaundice → carcinoma head of pancreas until proven otherwise. Ultrasound next.