Thématique :
- Foie
Originalité :
Solidité :
Doit faire évoluer notre pratique :
Dans certains cas
Nom du veilleur :
Docteur Bertrand HANSLIK
Coup de coeur :
  2016 May;65(5):852-60  
  doi: 10.1136/gutjnl-2014-308353  
  Tenofovir monotherapy versus tenofovir and entecavir combination therapy in patients with entecavir-resistant chronic hepatitis B with multiple drug failure: results of a randomised trial.  
  Lim YS, Byun KS, Yoo BC, Kwon SY, Kim YJ, An J, Lee HC, Lee YS  


Little clinical data are available regarding the optimal treatment of patients who harbour entecavir (ETV)-resistant HBV.


In this multicentre randomised trial, patients who had HBV with ETV resistance-associated mutations and serum HBV DNA concentrations >60 IU/mL were randomised to receive tenofovir disoproxil fumarate (TDF, 300 mg/day) monotherapy (n=45) or TDF and ETV (1 mg/day) combination therapy (n=45) for 48 weeks.


Baseline characteristics were comparable between groups, including HBV DNA levels (median, 4.02 log10 IU/mL) and hepatitis B e antigen-positivity (89%). All patients had at least one ETV-resistance mutation: rtT184A/C/F/G/I/L/S (n=49), rtS202G (n=43) and rtM250L/V (n=7), in addition to rtM204V/I (n=90). All except one patient in the TDF group completed 48 weeks of treatment. At week 48, the proportion of patients with HBV DNA <15 IU/mL, the primary efficacy endpoint, was not significantly different between the TDF and TDF+ETV groups (71% vs 73%; p>0.99). The mean change in HBV DNA levels from baseline was not significantly different between groups (-3.66 vs -3.74 log10 IU/mL; p=0.81). Virological breakthrough occurred in one patient on TDF, which was attributed to poor drug adherence. At week 48, six and three patients in the TDF and TDF+ETV groups, respectively, retained their baseline resistance mutations (p>0.99). None developed additional resistance mutations. Safety profiles were comparable in the two groups.


TDF monotherapy for 48 weeks provided a virological response comparable to that of TDF and ETV combination therapy in patients infected with ETV-resistant HBV.

Question posée
Patients résistants à l’entécavir : comparaison entre addition ou remplacement par le ténofovir.
Question posée
Le switch fait aussi bien que l’add on (ADN <15 UI : 72% à 48 semaines).

Etude ouverte chez des patients asiatiques (89% HBe). Seulement 5% de seroconversion HBe.