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Entecavir Resistance with Lamivudine — SCE Infectious Diseases MCQ

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HardHepatitisEntecavir Resistance with LamivudineSCE Infectious Diseases

A 40-year-old man with chronic hepatitis B has been on Entecavir for 3 years. He now has evidence of Lamivudine resistance (rtM204V mutation). His HBV DNA is rising despite Entecavir 0.5 mg daily. Why is this occurring?

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Correct answer: C — Entecavir has reduced efficacy in the presence of pre-existing Lamivudine resistance (rtM204V) — a higher Entecavir dose (1 mg daily) or switch to Tenofovir is needed

Entecavir has a higher genetic barrier to resistance in treatment-naive patients (<1% at 5 years). However, pre-existing Lamivudine resistance mutations (rtM204V/I) lower the genetic barrier to Entecavir resistance — resistance rates increase to ~50% by 5 years in Lamivudine-experienced patients. For this reason, Entecavir 1 mg daily (double dose) is recommended for Lamivudine-refractory patients, or preferably a switch to Tenofovir (which has no cross-resistance with Lamivudine). EASL recommends Tenofovir as the preferred rescue agent.

Reference: NICE CG165 2013 – Hepatitis B; EASL 2024 – HBV guidelines