Περίληψη:
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. © The Author 2015. Published by Oxford University Press for the Infectious Diseases Society of America.
Συγγραφείς:
Hermans, L.E.
Svicher, V.
Pas, S.D.
Salpini, R.
Alvarez, M.
Ben Ari, Z.
Boland, G.
Bruzzone, B.
Coppola, N.
Seguin-Devaux, C.
Dyda, T.
Garcia, F.
Kaiser, R.
Köse, S.
Krarup, H.
Lazarevic, I.
Lunar, M.M.
Maylin, S.
Micheli, V.
Mor, O.
Paraschiv, S.
Paraskevis, D.
Poljak, M.
Puchhammer-Stöckl, E.
Simon, F.
Stanojevic, M.
Stene-Johansen, K.
Tihic, N.
Trimoulet, P.
Verheyen, J.
Vince, A.
Weis, N.
Yalcinkaya, T.
Lepej, S.Z.
Perno, C.
Boucher, C.A.B.
Wensing, A.M.J.
Λέξεις-κλειδιά:
adefovir; adefovir plsu entecavir plus lamivudine; adefovir plus lamivudine; adefovir plus lamivudine plus telbivudine plus tenofovir; alanine; asparagine; entecavir; entecavir plus lamivudine; entecavir plus lamivudine plus tenofovir; isoleucine; lamivudine; lamivudine plus tenofovir; methionine; nucleoside derivative; nucleotide derivative; telbivudine; tenofovir; threonine; unclassified drug; valine; virus DNA; antivirus agent, adult; age; antiviral resistance; Article; blood level; chronic hepatitis B; DNA blood level; DNA determination; drug exposure; Europe; female; genetic screening; genotype; health survey; Hepatitis B virus; human; major clinical study; male; monotherapy; multicenter study; nonhuman; patient monitoring; prevalence; priority journal; risk assessment; risk factor; tertiary care center; virus load; virus mutation; antiviral resistance; clinical trial; cross-sectional study; drug effects; genetics; Hepatitis B virus; Hepatitis B, Chronic; middle aged; prevalence; virology, Adult; Antiviral Agents; Cross-Sectional Studies; Drug Resistance, Viral; Female; Genotype; Hepatitis B virus; Hepatitis B, Chronic; Humans; Male; Middle Aged; Prevalence
