Combined analysis of the prevalence of drug-resistant Hepatitis B virus in antiviral therapy-experienced patients in Europe (CAPRE)

Lucas Etienne Hermans, Valentina Svicher, Suzan Diepstraten Pas, Romina Salpini, Marta Alvarez, Ziv Ben Ari, Greet Boland, Bianca Bruzzone, Nicola Coppola, Carole Seguin-Devaux, Tomasz Dyda, Federico Garcia, Rolf Kaiser, Sukran Köse, Henrik Krarup, Ivana Lazarevic, Maja M. Lunar, Sarah Maylin, Valeria Micheli, Orna MorSimona Paraschiv, Dimitrios Paraskevis, Mario Poljak, Elisabeth Puchhammer-Stöckl, François Simon, Maja Stanojevic, Kathrine Stene-Johansen, Nijaz Tihic, Pascale Trimoulet, Jens Verheyen, Adriana Vince, Nina Weis, Tülay Yalcinkaya, Snjezana Zidovec Lepej, Carlo Perno, Charles A.B. Boucher, Annemarie M.J. Wensing*

*Corresponding author for this work

Research output: Contribution to journalArticleResearchpeer-review

25 Citations (Scopus)


Background European guidelines recommend treatment of chronic hepatitis B virus infection (CHB) with the nucleos(t)ide analogs (NAs) entecavir or tenofovir. However, many European CHB patients have been exposed to other NAs, which are associated with therapy failure and resistance. The CAPRE study was performed to gain insight in prevalence and characteristics of NA resistance in Europe. Methods A survey was performed on genotypic resistance testing results acquired during routine monitoring of CHB patients with detectable serum hepatitis B virus DNA in European tertiary referral centers. Results Data from 1568 patients were included. The majority (73.8%) were exposed to lamivudine monotherapy. Drug-resistant strains were detected in 52.7%. The most frequently encountered primary mutation was M204V/I (48.7%), followed by A181T/V (3.8%) and N236T (2.6%). In patients exposed to entecavir (n = 102), full resistance was present in 35.3%. Independent risk factors for resistance were age, viral load, and lamivudine exposure (P <. 001). Conclusions These findings support resistance testing in cases of apparent NA therapy failure. This survey highlights the impact of exposure to lamivudine and adefovir on development of drug resistance and cross-resistance. Continued use of these NAs needs to be reconsidered at a pan-European level.

Original languageEnglish
Pages (from-to)39-48
Number of pages10
JournalJournal of Infectious Diseases
Issue number1
Publication statusPublished - 1 Jan 2016


  • antiviral drug resistance; genotypic resistance testing; hepatitis B virus; nucleos(t)ide analogs


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