%0 Journal Article
%A Colagrossi, Luna
%A Hermans, Lucas E
%A Salpini, Romina
%A Di Carlo, Domenico
%A Pas, Suzan D
%A Alvarez, Marta
%A Ben-Ari, Ziv
%A Boland, Greet
%A Bruzzone, Bianca
%A Coppola, Nicola
%A Seguin-Devaux, Carole
%A Dyda, Tomasz
%A Garcia, Federico
%A Kaiser, Rolf
%A Köse, Sukran
%A Krarup, Henrik
%A Lazarevic, Ivana
%A Lunar, Maja M
%A Maylin, Sarah
%A Micheli, Valeria
%A Mor, Orna
%A Paraschiv, Simona
%A Paraskevis, Dimitros
%A Poljak, Mario
%A Puchhammer-Stöckl, Elisabeth
%A Simon, François
%A Stanojevic, Maja
%A Stene-Johansen, Kathrine
%A Tihic, Nijaz
%A Trimoulet, Pascale
%A Verheyen, Jens
%A Vince, Adriana
%A Lepej, Snjezana Zidovec
%A Weis, Nina
%A Yalcinkaya, Tülay
%A Boucher, Charles A B
%A Wensing, Annemarie M J
%A Perno, Carlo F
%A Svicher, Valentina
%A HEPVIR working group of the European Society for translational antiviral research (ESAR)
%T Immune-escape mutations and stop-codons in HBsAg develop in a large proportion of patients with chronic HBV infection exposed to anti-HBV drugs in Europe.
%D 2018
%U http://hdl.handle.net/10668/12535
%X HBsAg immune-escape mutations can favor HBV-transmission also in vaccinated individuals, promote immunosuppression-driven HBV-reactivation, and increase fitness of drug-resistant strains. Stop-codons can enhance HBV oncogenic-properties. Furthermore, as a consequence of the overlapping structure of HBV genome, some immune-escape mutations or stop-codons in HBsAg can derive from drug-resistance mutations in RT. This study is aimed at gaining insight in prevalence and characteristics of immune-associated escape mutations, and stop-codons in HBsAg in chronically HBV-infected patients experiencing nucleos(t)ide analogues (NA) in Europe. This study analyzed 828 chronically HBV-infected European patients exposed to ≥ 1 NA, with detectable HBV-DNA and with an available HBsAg-sequence. The immune-associated escape mutations and the NA-induced immune-escape mutations sI195M, sI196S, and sE164D (resulting from drug-resistance mutation rtM204 V, rtM204I, and rtV173L) were retrieved from literature and examined. Mutations were defined as an aminoacid substitution with respect to a genotype A or D reference sequence. At least one immune-associated escape mutation was detected in 22.1% of patients with rising temporal-trend. By multivariable-analysis, genotype-D correlated with higher selection of ≥ 1 immune-associated escape mutation (OR[95%CI]:2.20[1.32-3.67], P = 0.002). In genotype-D, the presence of ≥ 1 immune-associated escape mutations was significantly higher in drug-exposed patients with drug-resistant strains than with wild-type virus (29.5% vs 20.3% P = 0.012). Result confirmed by analysing drug-naïve patients (29.5% vs 21.2%, P = 0.032). Strong correlation was observed between sP120T and rtM204I/V (P  Immune-escape mutations and stop-codons develop in a large fraction of NA-exposed patients from Europe. This may represent a potential threat for horizontal and vertical HBV transmission also to vaccinated persons, and fuel drug-resistance emergence.
%K Drug-resistance
%K HBV
%K HBsAg
%K Immune-escape
%K Stop-codons
%~