Case Study #3 Lamivudine (LMV) + Entecavir (ETV) Resistance

LMV + ETV Resistance

  • 57 year old male recurrent HBV disease following Orthotopic Liver Transplant
  • – Italian-born, no other risk factors
  • HBsAg +ve, HBeAg -ve, anti-HBe +ve
  • Patient underwent a liver transplant

Virological Breakthrough on LMV

  1. Patient commenced LMV monotherapy
    • Initial suppression of viral replication
    • Serum ALT levels normalise
  2. Patient experienced virological breakthrough
    • HBV DNA levels rapidly increased to pre-therapy levels
    • Serum ALT levels flared
The patient was maintained on LMV monotherapy

LMV resistance

Drug resistance testing:

  1. Antiviral drug resistance testing was performed following virological breakthrough on LMV
    • The primary resistance mutations to LMV rtL180M and rtM204V ( + rtV173L) were detected
    • Patient commenced treatment with 1.0 mg of ETV monotherapy
The initial response to ETV was excellent with both HBV DNA and ALT levels dropping significantly

ETV Resistance

  1. Patient commenced ETV monotherapy.
    • Excellent initial response
    • both HBV DNA and ALT levels dropped significantly
  2. Virological breakthrough occurred again on ETV monotherapy
  3. Rescue therapy included the addition of LMV
  4. ETV was removed and ADV was added to LMV briefly. The patient was then continued on ADV monotherapy

ETV Resistance

Drug resistance testing:

  1. Antiviral drug resistance testing was performed following virological breakthrough on ETV
    • The primary resistance mutations to ETV rtL180M + rtT184G + rtS202I + rtM204V were detected