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本帖最后由 StephenW 于 2015-12-12 13:28 编辑
Combined Analysis of the Prevalence of Drug-Resistant Hepatitis B Virus in Antiviral Therapy–Experienced Patients in Europe (CAPRE) - Lucas Etienne Hermans1,2,a,
- Valentina Svicher3,a,
- Suzan Diepstraten Pas2,
- Romina Salpini3,
- Marta Alvarez4,
- Ziv Ben Ari5,
- Greet Boland1,
- Bianca Bruzzone6,
- Nicola Coppola7,
- Carole Seguin-Devaux8,
- Tomasz Dyda9,
- Federico Garcia4,
- Rolf Kaiser10,
- Sukran Köse11,
- Henrik Krarup12,
- Ivana Lazarevic13,
- Maja M. Lunar14,
- Sarah Maylin15,
- Valeria Micheli16,
- Orna Mor17,
- Simona Paraschiv18,
- Dimitrios Paraskevis19,
- Mario Poljak14,
- Elisabeth Puchhammer-Stöckl20,
- François Simon15,
- Maja Stanojevic13,
- Kathrine Stene-Johansen21,
- Nijaz Tihic22,
- Pascale Trimoulet23,
- Jens Verheyen24,
- Adriana Vince25,
- Nina Weis26,
- Tülay Yalcinkaya27,
- Snjezana Zidovec Lepej25,
- Carlo Perno3,
- Charles A. B. Boucher2 and
- Annemarie M. J. Wensing1
- on behalf of the HEPVIR working group of the European Society for Translational Antiviral Research (ESAR)
- 1Department of Medical Microbiology, University Medical Centre Utrecht
- 2Department of Virology, Erasmus Medical Centre, Rotterdam, The Netherlands
- 3Department of Experimental Medicine and Surgery, University of Rome Tor Vergata, Italy
- 4Servicio de Microbiología, Hospital San Cecilio, Instituto de Investigación Biosanitaria ibs. GRANADA, Hospitales Universitarios de Granada, Spain
- 5Liver Disease Centre, Sheba Medical Centre, Ramat Gan, Israel
- 6Hygiene Unit, IRCCS AOU San Martino - IST, Genoa
- 7Malattie Infettive, Seconda Università degli studi di Napoli, Naples, Italy
- 8Laboratory of Retrovirology, CRP-Santé, Luxembourg
- 9Molecular Diagnostics Laboratory, Hospital of Infectious Diseases, Warsaw, Poland
- 10Institute of Virology, University of Cologne, Germany
- 11Clinic of Infectious Diseases and Clinical Microbiology, Izmir Tepecik Education and Research Hospital, Turkey
- 12Section of Molecular Diagnostics, Clinical Biochemistry, Aalborg University Hospital, Denmark
- 13Institute of Microbiology and Immunology, Faculty of Medicine, University of Belgrade, Serbia
- 14Institute of Microbiology and Immunology, Faculty of Medicine, University of Ljubljana, Slovenia
- 15Service de Microbiologie, University Paris Diderot, Hôpital Saint Louis, France
- 16Lugi Sacco Hospital, Milan, Italy
- 17National HIV Reference Laboratory, Central Virology Laboratory, Ministry of Health, Tel Hashomer, Ramat Gan, Israel
- 18Molecular Diagnostics Laboratory, National Institute for Infectious Diseases Matei Bals, Bucharest, Romania
- 19National Retrovirus Reference Centre, Department of Hygiene, Epidemiology and Medical Statistics, Faculty of Medicine, National and Kapodistrian University of Athens, Greece
- 20Department for Virology, Medical University of Vienna, Austria
- 21Department of Virology, Norwegian Institute of Public Health, Oslo, Norway
- 22Institute of Microbiology, Polyclinic for Laboratory Diagnostics, University Clinical Centre Tuzla, Bosnia and Herzegovina
- 23Virology Laboratory, Centre Hospitalier Régional et Université Victor Segalen, Bordeaux, France
- 24Institute of Virology, University-Hospital, University Duisburg-Essen, Germany
- 25University of Zagreb School of Medicine and University Hospital for Infectious Diseases “Dr Fran Mihaljevic”, Croatia
- 26Department of Infectious Diseases, Copenhagen University Hospital, Denmark
- 27Refik Saydam National Public Health Agency, Ankara, Turkey
- Correspondence: A. M. J. Wensing, Department of Medical Microbiology, University Medical Centre Utrecht – Virology, G04.614, Heidelberglaan 100, 3584 CX Utrecht, The Netherlands (a.m.j.wensing{at}umcutrecht.nl).
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.
Key words
antiviral drug resistance genotypic resistance testing hepatitis B virus nucleos(t)ide analogs
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发表于 2015-12-12 13:27
