HBeAg defective mu tants in active/inactive anti-HBe positive HBV carriers: possible role of pre-core initiation mutants

FLICHMAN D, CAVALLONE D, BIAGIONI R, OLIVERI F, CICCOROSSI P, COCO B, COLOMBATTO P, SACCO R, BONINO F, BRUNETTO M.

Paris

Simposio; 12th International Symposium on Viral Hepatitis and Liver Disease; 2006

European Association for the Study of the Liver

Background and Aim: Mutations that modulate HBeAg expressionat translational or transcriptional levels are present in anti-HBe-positiveHBsAg carriers, but their relationship with active and inactive infection isunclear.Materials and Methods: We characterized by direct sequencing BasicCore Promoter (BCP) and pre-Core (pC) HBV mutants in 104 chronicanti-HBe positive carriers, followed prospectively for 25.3 months (range:12 32) and classified as inactive (26) or active (78) according to 12 monthpersistence of normal ALT and HBV-DNA levels <5 log10 cp/ml.Results: BCP and pC mutants were found in all cases [1762T: 60.8%;1764A: 68.6%; 1896A: 72.5%; 1899A: 52.0%; 2bp insertion 1.0%;1817T: 2.9% and pre-Core initiation codon (PIC): 10.8%]. The 1896Asingle mutation pattern prevailed in younger than older (>50 years) carriers(29.6% vs. 0.0%, p <0.001). Mutations at nt 1762, 1764 and 1896 hadlower prevalence in inactive than active carriers [37.5% vs 67.9% (p 0.009),45.8% vs 75.6% (p 0.011), 58.3% vs 76.9% (n.s.)] respectively; whereas1899 mutation was evenly distributed in the 2 groups (50% vs 53%). PICvariants prevailed in inactive HBV genotype D carriers (29.2% vs 5.3%,p <0.003) and were associated with ALT flares in active carriers.Conclusions: BCP/pC mutations are the hallmark of chronic anti-HBepositive HBV infection. Translational pC mutants prevail in youngerwhereas transcriptional BCP mutants might provide selective viral fitnessin older and active HBV carriers. PIC mutations in inactive HBV genotypeD carriers might play a role in shifting from active to inactive infection.