LAUSR

Selection of HBeAg defective HBV mutants (mt) during childhood might influence infection outcome in adults. Aim of this study was to correlate the dynamics of pre‐core HBV mutant (pre‐C mt) selection with virological/clinical outcomes in children followed‐up until adulthood. Eighty subjects (50‐M/30‐F), 70 HBeAg‐positive (87.5%), and 10 (12.5%) HBeAg‐negative/anti‐HBe‐positive at the admission, mostly genotype D infected (91.2%), with median age of 6.5 (range: 0.2‐17) years, were followed‐up for 14.3 years (range: 1.1‐24.5); 46 (57.5%) received IFN treatment. HBV‐DNA and q‐HBsAg were tested by commercial assays, Pre‐Core 1896 mt by direct‐sequence, oligo‐hybridization‐assay, and allele‐specific‐PCR (sensitivity: 30%, 10%, and 0.1% of total viremia). HBeAg/anti‐HBe seroconversion (SC) occurred in 55/70 (78.6%) children. After SC, 8 (14.6%) developed HBeAg‐negative chronic hepatitis (CHB), 41 (74.5%) remain with HBeAg‐negative chronic infection, and 6 (10.9%) lost HBsAg. Baseline HBV‐DNA and HBsAg were lower in SC than in no‐SC children (median: 7.35 vs 8.95 Log IU/mL, P = 0.005, and 4.72 vs 5.04 Log IU/mL, P = 0.015). The prevalence of pre‐C mt increased rapidly (10‐40%) around SC. Eventually, pre‐C mt was detected in 100% of CHB, in 33% of chronic infections without disease, and in 16% of subjects who cleared HBsAg (P < 0.001). HBV‐DNA levels remained slightly higher in carriers of HBeAg negative infection with dominant/mixed pre‐C mt populations, than in those with dominant pre‐C wt (mean Log IU/mL: 3.83 and 3.42 vs 2.67, P = 0.007). In conclusion, pre‐C‐mt is selected during HBeAg/anti‐HBe SC in children with poor control of HBV replication, leading to HBeAg‐negative chronic‐active‐hepatitis during adulthood.