Pretreatment viral quasispecies characteristics and evolutionary phases correlate with HBsAg seroconversion in peginterferon-alfa-2a-treated children with HBeAg-positive chronic hepatitis B.

BACKGROUND & AIMS: To evaluate baseline HBV quasispecies (QS) characteristics as a predictor of HBsAg seroconversion in peginterferon-alfa-2a-treated HBeAg-positive pediatric chronic hepatitis B (CHB).

METHODS

25 patients achieved HBsAg seroconversion (SS group) and another 25 did not (SN group) were enrolled, matched for baseline profiles. Full-length HBV genomes were obtained from pretreatment serum via clone sequencing. Twelve untreated carriers (CA group) served as controls.

RESULTS

SN group demonstrated significantly higher genetic distance (GD) and mutation frequency index (MFI) in the preCore/Core (preC/C) gene versus SS and CA groups (p < 0.05). Treatment failure exclusively correlated with G1896A/C1913A/C2078G mutations. Jonckheere-Terpstra test confirmed a CA→SS→SN diversity gradient in preC/C (p < 0.05). Non-invasive fibrosis indices increased across CA→SS→SN (p < 0.05) and correlated positively with QS diversity. Evolutionary analyses revealed divergent haplotype clustering in SN versus star-like radiation patterns in CA/SS. Phylogenetic analysis positioned CA/SS haplotypes at earlier evolutionary phases, while SN haplotypes at a later phase. Notably, haplotypes harboring the three aforementioned mutations were also located at the later phase. Positive selection analysis identified two SN-specific mutations (codon 34[C1913A] and 89[C2078G]). A LASSO-derived predictive model (age, C1913A/C2078G, preC/C MFI) yielded the area under the receiver operating characteristic curve (AUROC) 0.814 (sensitivity 92 %, specificity 68 %).

CONCLUSIONS

Lower baseline HBV quasispecies diversity predicts Peginterferon-alfa-2a-induced HBsAg seroconversion in pediatric CHB. The observed diversity continuum, association with fibrosis indices, suggests seroconversion occurs preferentially during earlier hepatitis phases. Pretreatment viral genetic profiling may optimize therapeutic timing, highlighting its prognostic value for childhood HBV management.