title: Combined Analysis of the Prevalence of Drug-Resistant Hepatitis B Virus in Antiviral Therapy-Experienced Patients in Europe (CAPRE).
abstract: 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.
authors.affiliation: Department of Medical Microbiology, University Medical Centre Utrecht Department of Virology, Erasmus Medical Centre, Rotterdam, The Netherlands.
authors.forename: Lucas Etienne
authors.initials: LE
authors.lastname: Hermans
authors.affiliation: Department of Experimental Medicine and Surgery, University of Rome Tor Vergata, Italy.
authors.forename: Valentina
authors.initials: V
authors.lastname: Svicher
authors.affiliation: Department of Virology, Erasmus Medical Centre, Rotterdam, The Netherlands.
authors.forename: Suzan Diepstraten
authors.initials: SD
authors.lastname: Pas
authors.affiliation: Department of Experimental Medicine and Surgery, University of Rome Tor Vergata, Italy.
authors.forename: Romina
authors.initials: R
authors.lastname: Salpini
authors.affiliation: Servicio de Microbiología, Hospital San Cecilio, Instituto de Investigación Biosanitaria ibs. GRANADA, Hospitales Universitarios de Granada, Spain.
authors.forename: Marta
authors.initials: M
authors.lastname: Alvarez
authors.affiliation: Liver Disease Centre, Sheba Medical Centre, Ramat Gan, Israel.
authors.forename: Ziv
authors.initials: Z
authors.lastname: Ben Ari
authors.affiliation: Department of Medical Microbiology, University Medical Centre Utrecht.
authors.forename: Greet
authors.initials: G
authors.lastname: Boland
authors.affiliation: Hygiene Unit, IRCCS AOU San Martino - IST, Genoa.
authors.forename: Bianca
authors.initials: B
authors.lastname: Bruzzone
authors.affiliation: Malattie Infettive, Seconda Università degli studi di Napoli, Naples, Italy.
authors.forename: Nicola
authors.initials: N
authors.lastname: Coppola
authors.affiliation: Laboratory of Retrovirology, CRP-Santé, Luxembourg.
authors.forename: Carole
authors.initials: C
authors.lastname: Seguin-Devaux
authors.affiliation: Molecular Diagnostics Laboratory, Hospital of Infectious Diseases, Warsaw, Poland.
authors.forename: Tomasz
authors.initials: T
authors.lastname: Dyda
authors.affiliation: Servicio de Microbiología, Hospital San Cecilio, Instituto de Investigación Biosanitaria ibs. GRANADA, Hospitales Universitarios de Granada, Spain.
authors.forename: Federico
authors.initials: F
authors.lastname: Garcia
authors.affiliation: Institute of Virology, University of Cologne, Germany.
authors.forename: Rolf
authors.initials: R
authors.lastname: Kaiser
authors.affiliation: Clinic of Infectious Diseases and Clinical Microbiology, Izmir Tepecik Education and Research Hospital, Turkey.
authors.forename: Sukran
authors.initials: S
authors.lastname: Köse
authors.affiliation: Section of Molecular Diagnostics, Clinical Biochemistry, Aalborg University Hospital, Denmark.
authors.forename: Henrik
authors.initials: H
authors.lastname: Krarup
authors.affiliation: Institute of Microbiology and Immunology, Faculty of Medicine, University of Belgrade, Serbia.
authors.forename: Ivana
authors.initials: I
authors.lastname: Lazarevic
authors.affiliation: Institute of Microbiology and Immunology, Faculty of Medicine, University of Ljubljana, Slovenia.
authors.forename: Maja M
authors.initials: MM
authors.lastname: Lunar
authors.affiliation: Service de Microbiologie, University Paris Diderot, Hôpital Saint Louis, France.
authors.forename: Sarah
authors.initials: S
authors.lastname: Maylin
authors.affiliation: Lugi Sacco Hospital, Milan, Italy.
authors.forename: Valeria
authors.initials: V
authors.lastname: Micheli
authors.affiliation: National HIV Reference Laboratory, Central Virology Laboratory, Ministry of Health, Tel Hashomer, Ramat Gan, Israel.
authors.forename: Orna
authors.initials: O
authors.lastname: Mor
authors.affiliation: Molecular Diagnostics Laboratory, National Institute for Infectious Diseases Matei Bals, Bucharest, Romania.
authors.forename: Simona
authors.initials: S
authors.lastname: Paraschiv
authors.affiliation: National Retrovirus Reference Centre, Department of Hygiene, Epidemiology and Medical Statistics, Faculty of Medicine, National and Kapodistrian University of Athens, Greece.
authors.forename: Dimitrios
authors.initials: D
authors.lastname: Paraskevis
authors.affiliation: Institute of Microbiology and Immunology, Faculty of Medicine, University of Ljubljana, Slovenia.
authors.forename: Mario
authors.initials: M
authors.lastname: Poljak
authors.affiliation: Department for Virology, Medical University of Vienna, Austria.
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Puchhammer-Stöckl
authors.affiliation: Service de Microbiologie, University Paris Diderot, Hôpital Saint Louis, France.
authors.forename: François
authors.initials: F
authors.lastname: Simon
authors.affiliation: Institute of Microbiology and Immunology, Faculty of Medicine, University of Belgrade, Serbia.
authors.forename: Maja
authors.initials: M
authors.lastname: Stanojevic
authors.affiliation: Department of Virology, Norwegian Institute of Public Health, Oslo, Norway.
authors.forename: Kathrine
authors.initials: K
authors.lastname: Stene-Johansen
authors.affiliation: Institute of Microbiology, Polyclinic for Laboratory Diagnostics, University Clinical Centre Tuzla, Bosnia and Herzegovina.
authors.forename: Nijaz
authors.initials: N
authors.lastname: Tihic
authors.affiliation: Virology Laboratory, Centre Hospitalier Régional et Université Victor Segalen, Bordeaux, France.
authors.forename: Pascale
authors.initials: P
authors.lastname: Trimoulet
authors.affiliation: Institute of Virology, University-Hospital, University Duisburg-Essen, Germany.
authors.forename: Jens
authors.initials: J
authors.lastname: Verheyen
authors.affiliation: University of Zagreb School of Medicine and University Hospital for Infectious Diseases "Dr Fran Mihaljevic", Croatia.
authors.forename: Adriana
authors.initials: A
authors.lastname: Vince
authors.affiliation: Department of Infectious Diseases, Copenhagen University Hospital, Denmark.
authors.forename: Nina
authors.initials: N
authors.lastname: Weis
authors.affiliation: Refik Saydam National Public Health Agency, Ankara, Turkey.
authors.forename: Tülay
authors.initials: T
authors.lastname: Yalcinkaya
authors.affiliation: University of Zagreb School of Medicine and University Hospital for Infectious Diseases "Dr Fran Mihaljevic", Croatia.
authors.forename: Snjezana Zidovec
authors.initials: SZ
authors.lastname: Lepej
authors.affiliation: Department of Experimental Medicine and Surgery, University of Rome Tor Vergata, Italy.
authors.forename: Carlo
authors.initials: C
authors.lastname: Perno
authors.affiliation: Department of Virology, Erasmus Medical Centre, Rotterdam, The Netherlands.
authors.forename: Charles A B
authors.initials: CA
authors.lastname: Boucher
authors.affiliation: Department of Medical Microbiology, University Medical Centre Utrecht.
authors.forename: Annemarie M J
authors.initials: AM
authors.lastname: Wensing
mesh_terms: D000328:Adult; D000998:Antiviral Agents / Q000494:pharmacology* / Q000627:therapeutic use; D003430:Cross-Sectional Studies; D024882:Drug Resistance, Viral / Q000235:genetics*; D005260:Female; D005838:Genotype; D006515:Hepatitis B virus / Q000187:drug effects* / Q000235:genetics*; D019694:Hepatitis B, Chronic / Q000188:drug therapy / Q000453:epidemiology* / Q000821:virology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D015995:Prevalence
chemical_list: D000998:Antiviral Agents
keywords: antiviral drug resistance; genotypic resistance testing; hepatitis B virus; nucleos(t)ide analogs