428 VERTICAL HEPATITIS B VIRUS TRANSMISSION DESPITE SEROVACCINATION OF THE NEWBORN IN HIGHLY VIRAEMIC MONO-INFECTED MOTHERS FROM VARIOUS ETHNIC ORIGINS: A RETROSPECTIVE STUDY IN PARIS, FRANCE

4/8 (50%) rapidly developed lamivudine-resistance mutations. Patients with HBV-reactivation were characterized by a degree of HBsAg-variability higher than that in stably-HBV-infected patients, particularly in a-determinant critical for modulating HBVinfectivity and evasion from neutralizing-antibodies (mean geneticdivergence: 0.058 versus 0.017, P < 0.001). Furthermore, both the percentage of patients with at least 1 immune-escape mutation, and the median number of immune-escape mutations in a-determinant, were significantly higher in patients with HBV-reactivation than in controls (64.3%[9/14] versus 27%[27/100], P = 0.008; and 1[IQR: 0–2] versus 0[IQR: 0–2], P = 0.002, respectively). Moreover, ≥1 specific HBsAg-mutation (M103I-T123N-S143L-D144E-S154L-V190A) was present in 8/14 (57.1%) patients with HBV-reactivation status (independently from the presence of drug-resistance mutations), while in controls they were absent (0/100 for M103I-T123ND144E-S154L), or nearly absent (1/100 for S143L and 2/100 for V190A). All the identified mutations (except for V190A, situated in the membrane-embedded C-terminal domain) are localized in a-determinant, and are known to be associated with decreased HBsAg-antigenicity. T123N introduces an N-linked glycosylationsite, thus potentially reducing HBsAg immunogenic-surface. Conclusions: HBV-reactivation correlates with an increased HBV ability to evade the pressure imposed by humoral immuneresponse. This highlights the need of a careful monitoring, and of establishing an adequate, high-genetic-barrier therapy (if required) in order to prevent HBV-reactivation and consequent liver damage in the setting of immune-suppression.