Paper II
2014 September (Supplementary) (2010 Scheme) · 40 marks · 120 min

Question

Discuss the laboratory diagnosis of hepatitis B virus Infection

Q35 marksShort Essays

Answer

Laboratory diagnosis of Hepatitis B virus (HBV) infection relies on a panel of serological markers, whose combined pattern indicates the phase of infection (acute, chronic, resolved, or immunized) — this “serological window” approach is central to HBV diagnosis, since no single marker alone provides complete information.

Key markers:

  • HBsAg (Hepatitis B surface antigen) — the first marker to appear (within weeks of infection), indicating current infection (acute or chronic); persistence beyond 6 months defines chronic HBV infection; the target antigen of the HBV vaccine.
  • Anti-HBs (antibody to HBsAg) — indicates recovery with immunity from natural infection, or successful vaccination; its presence (in the absence of anti-HBc) specifically indicates vaccine-induced immunity, since the vaccine contains only HBsAg.
  • HBcAg (core antigen) — not detectable in serum by routine testing (remains sequestered within the virion/infected hepatocyte), but its corresponding antibody (anti-HBc) is a key serological marker.
  • Anti-HBc (antibody to core antigen):
    • IgM anti-HBc — indicates recent/acute infection (appears early and is a useful marker during the “window period,” when HBsAg may have already disappeared but anti-HBs has not yet risen).
    • IgG anti-HBc — persists long-term, indicating past or current infection (present in both resolved and chronic infection, but notably absent after vaccination, an important distinguishing feature from anti-HBs-positive-only vaccinated individuals).
  • HBeAg (e antigen) — a marker of active viral replication and high infectivity; correlates with high viral load.
  • Anti-HBe — its appearance (seroconversion from HBeAg) generally indicates reduced viral replication and lower infectivity, though “precore mutant” strains can replicate actively despite being HBeAg-negative/anti-HBe-positive.
  • HBV DNA (quantitative PCR/viral load) — the most direct and sensitive marker of active viral replication, used for monitoring disease activity and treatment response in chronic infection.

Interpretation patterns (illustrative):

  • Acute infection: HBsAg+, IgM anti-HBc+, HBeAg+ (usually).
  • Window period: HBsAg negative, anti-HBs not yet positive, but IgM anti-HBc positive — the only detectable marker during this interval.
  • Chronic infection: HBsAg+ (>6 months), IgG anti-HBc+, HBeAg+/− depending on replicative phase.
  • Resolved infection: HBsAg negative, anti-HBs+, IgG anti-HBc+.
  • Vaccinated (never infected): anti-HBs+ only, anti-HBc negative.

Other methods: liver function tests (ALT/AST) to assess hepatocellular injury; liver biopsy/elastography for assessing fibrosis in chronic infection.

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