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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 [Elektronski vir]Colagrossi, Luna ...Background: 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 consequ ence of the overlapping structure of HBV genome, some immune-escape mutations or stop-codons in HBsAg can deriv e from drug-resistance mutations in RT. This study is aimed at gaining insight in prevalence and characteristics of immu ne-associated escape mutation s, and stop-codons in HBsAg in chronically HBV-infected pati ents experiencing nucleos(t) ide analogues (NA) in Europe. Methods: 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-esc ape mutations sI195M, sI196S, and sE164D (resulting from drug-resistance mutati on rtM204 V, rtM204I, and rtV173L) were re trieved from literature and examined. Mutations were defined as an aminoacid substitution w ith respect to a genotype A or D reference sequence. Results: At least one immune-associated escape mutation was dete cted 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 analys ing drug-naïve patients (29.5% vs 21. 2%, P = 0.032). Strong correlation was observed between sP120T and rtM204I/V ( P < 0.001), and their co- presence determined an increased HBV-DNA. At least one NA-induced immune-escape mutation occurred in 28.6% of patients, and their selection correlated with genotype-A (OR[95%CI]:2.03[1.32 - 3.10], P = 0.001). Finally, stop-codons are present in 8.4% of patients also at HBsAg-positions 172 and 182, described to enhance viral oncogenic-properties. Conclusions: 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.Source: BMC infectious diseases [Elektronski vir]. - ISSN 1471-2334 (Vol. 18, no. 1, Jun. 2018, str. 1-12)Type of material - e-article ; adult, seriousPublish date - 2018Language - englishCOBISS.SI-ID - 33904089
Author
Colagrossi, Luna |
Hermans, Lucas Etienne |
Salpini, Romina |
Di Carlo, Domenico |
Diepstraten Pas, Suzan |
Alvarez, Marta |
Ben Ari, Ziv |
Boland, Greet |
Lunar, Maja M., 1982- |
Poljak, Mario, 1965-
Topics
HBV |
drug resistance |
treatment effectiveness |
HBV |
odpornost na zdravila |
učinkovitost zdravljenja
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Database name | Field | Year |
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Links to authors' personal bibliographies | Links to information on researchers in the SICRIS system |
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Colagrossi, Luna | ![]() |
Hermans, Lucas Etienne | ![]() |
Salpini, Romina | ![]() |
Di Carlo, Domenico | ![]() |
Diepstraten Pas, Suzan | ![]() |
Alvarez, Marta | ![]() |
Ben Ari, Ziv | ![]() |
Boland, Greet | ![]() |
Lunar, Maja M., 1982- | 54554 |
Poljak, Mario, 1965- | 11622 |
Source: Personal bibliographies
and: SICRIS
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