A 35-year-old HBsAg-positive patient shows HBeAg negativity, high HBV DNA (>2000 IU/mL) and elevated ALT. Anti-HBe is positive. What mutation is responsible for this pattern and what is its clinical significance?
- A YMDD motif mutation in reverse transcriptase — lamivudine resistance
- B Surface gene mutation — immune escape from anti-HBs vaccine
- C Precore stop codon mutation (G1896A) — prevents HBeAg secretion but virus replicates; associated with more severe liver disease ✓
- D Core promoter mutation — increased HBcAg expression
Explanation
HBeAg-negative chronic hepatitis B with high viral load is caused by precore or core promoter mutations. The commonest is the precore stop codon mutation at nucleotide 1896 (G→A), which creates a premature stop codon in the precore region, preventing translation and secretion of HBeAg, while the virus continues to replicate normally via core protein. Anti-HBe is positive reflecting seroconversion from HBeAg. This pattern represents occult high-replication hepatitis B with more aggressive liver disease and risk of cirrhosis/HCC. YMDD mutations cause lamivudine resistance. Surface gene mutations cause vaccine escape.
Reference: Ananthanarayan & Paniker's Textbook of Microbiology, 11th ed.
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Written and medically reviewed by the StethoPrep medical team.