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

• Published in: BMC infectious diseases 2018-06, Vol.18 (1), p.251-251, Article 251
• Main Authors: Colagrossi, Luna, Hermans, Lucas E, Salpini, Romina, Di Carlo, Domenico, Pas, Suzan D, Alvarez, Marta, Ben-Ari, Ziv, Boland, Greet, Bruzzone, Bianca, Coppola, Nicola, Seguin-Devaux, Carole, Dyda, Tomasz, Garcia, Federico, Kaiser, Rolf, Köse, Sukran, Krarup, Henrik, Lazarevic, Ivana, Lunar, Maja M, Maylin, Sarah, Micheli, Valeria, Mor, Orna, Paraschiv, Simona, Paraskevis, Dimitros, Poljak, Mario, Puchhammer-Stöckl, Elisabeth, Simon, François, Stanojevic, Maja, Stene-Johansen, Kathrine, Tihic, Nijaz, Trimoulet, Pascale, Verheyen, Jens, Vince, Adriana, Lepej, Snjezana Zidovec, Weis, Nina, Yalcinkaya, Tülay, Boucher, Charles A B, Wensing, Annemarie M J, Perno, Carlo F, Svicher, Valentina
• Format: Article
• Language: English
• Subjects: Activation; Adult; Amino Acid Substitution; Antigens; Antiviral Agents - therapeutic use; Chronic infection; Codon, Terminator; Codons; Correlation analysis; Deoxyribonucleic acid; Disease transmission; DNA; DNA sequencing; Dosage and administration; Drug resistance; Endoplasmic reticulum; Europe; Exposure; Female; Fitness; Genomes; Genotype; Genotype & phenotype; Genotypes; HBsAg; HBV; Hepatitis; Hepatitis B surface antigen; Hepatitis B Surface Antigens - genetics; Hepatitis B Surface Antigens - immunology; Hepatitis B vaccine; Hepatitis B virus; Hepatitis B virus - genetics; Hepatitis B virus - immunology; Hepatitis B, Chronic - drug therapy; Hepatitis B, Chronic - immunology; Hepatitis B, Chronic - virology; Humans; Immune evasion; Immune-escape; Immunoglobulins; Immunosuppression; Immunosuppressive agents; Infections; Infectious diseases; Male; Middle Aged; Mutation; Nucleotide sequence; Nucleotide sequencing; Patients; Reproductive fitness; Software; Stop-codons; Strains (organisms); Vaccination; Vaccines; Viruses
• ISSN: 1471-2334; 1471-2334
• DOI: 10.1186/s12879-018-3161-2

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