RT Journal Article
T1 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.
A1 Colagrossi, Luna
A1 Hermans, Lucas E
A1 Salpini, Romina
A1 Di Carlo, Domenico
A1 Pas, Suzan D
A1 Alvarez, Marta
A1 Ben-Ari, Ziv
A1 Boland, Greet
A1 Bruzzone, Bianca
A1 Coppola, Nicola
A1 Seguin-Devaux, Carole
A1 Dyda, Tomasz
A1 Garcia, Federico
A1 Kaiser, Rolf
A1 Köse, Sukran
A1 Krarup, Henrik
A1 Lazarevic, Ivana
A1 Lunar, Maja M
A1 Maylin, Sarah
A1 Micheli, Valeria
A1 Mor, Orna
A1 Paraschiv, Simona
A1 Paraskevis, Dimitros
A1 Poljak, Mario
A1 Puchhammer-Stöckl, Elisabeth
A1 Simon, François
A1 Stanojevic, Maja
A1 Stene-Johansen, Kathrine
A1 Tihic, Nijaz
A1 Trimoulet, Pascale
A1 Verheyen, Jens
A1 Vince, Adriana
A1 Lepej, Snjezana Zidovec
A1 Weis, Nina
A1 Yalcinkaya, Tülay
A1 Boucher, Charles A B
A1 Wensing, Annemarie M J
A1 Perno, Carlo F
A1 Svicher, Valentina
A1 HEPVIR working group of the European Society for translational antiviral research (ESAR), 
K1 Drug-resistance
K1 HBV
K1 HBsAg
K1 Immune-escape
K1 Stop-codons
AB 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.
YR 2018
FD 2018-06-01
LK http://hdl.handle.net/10668/12535
UL http://hdl.handle.net/10668/12535
LA en
DS RISalud
RD Apr 6, 2025