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J Med Virol. 2018 Feb 28. doi: 10.1002/jmv.25068. [Epub ahead of print]
HBV Pre-Core mutant in genotype-D infected children is selected during HBeAg/anti-HBe seroconversion and leads to HBeAg negative chronic hepatitis B in adulthood.Colombatto P1, Barbera C2, Bortolotti F3, Maina AM1, Moriconi F1, Cavallone D1, Calvo P2, Oliveri F1, Bonino F4, Brunetto MR1,5.
Author information
1Hepatology Unit and Laboratory of Molecular Genetics and Pathology of Hepatitis Viruses, Reference Centre of the Tuscany Region for Chronic Liver Disease and Cancer, University Hospital of Pisa, Pisa, Italy.2Paediatric Gastroenterology Unit, Regina Margherita Children Hospital, Torino, Italy.3University of Padova, Padova, Italy.4University of Pittsburgh Medical Center Institute for Health, Chianciano Terme, Siena, Italy, and Fondazione Italiana Fegato, AREA Science Park, Campus Basovizza, Trieste, Italy.5Internal Medicine, Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy.
AbstractBACKGROUND: 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.
METHODS: 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).
RESULTS: 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% to 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) Conclusions. 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. This article is protected by copyright. All rights reserved.
This article is protected by copyright. All rights reserved.
KEYWORDS: Antiviral agents, Genetic variability; Evolution, Persistent infection; Hepatitis B virus; Infection, Immune responses, Immune system; Pathogenesis; Virus classification, Interferon
PMID:29488227DOI:10.1002/jmv.25068
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