A COMPLEX HBV QUASISPECIES IN RT AND HBSAG CHARACTERIZES PATIENTS WITH ACUTE HEPATITIS B: A REFINED UDPS ANALYSIS Print
M. Aragri1, N. Coppola2, C. Alteri1, C. Minichini2, A. Battisti1, C. Sagnelli3, M.C. Bellocchi1, M.A. Pisaturo2, R. Salpini1, M. Starace2, F. Continenza4, D. Armenia1, L. Carioti1, M. Pollicita1, E. Sagnelli2, C.F. Perno1,5, V. Svicher1
1Department of Experimental Medicine and Surgery, University of Rome Tor Vergata, Rome, 2Department of Mental Health and Public Medicine, 3Department of Clinical and Experimental Medicine and Surgery, Second University of Naples, Naples, 4I.N.M.I. L. Spallanzani, 5Tor Vergata University Hospital, Rome, Italy
Background and aims: To investigate HBV-RT and HBsAg genetic heterogeneity in patients with acute hepatitis B (AHB) in Italy.
Methods: This study included 44 HBsAg+ and IgM/anti-HBc+ patients with a compatible clinical-history for AHB (all genotype-D) observed from 2000 to 2010. Plasma-samples obtained at the first-observation were used for population- and ultra-deep sequencing (UDPS). Immune-escape mutations were retrieved from literature.
Results: 68.2% of patients was male with median (IQR) age of 34 (27-46) years. Median (IQR) ALT and median (IQR) serum HBV-DNA were 2,717(2,035-3,319)U/L and 5.2(IQR:4.5-6.9)log10IU/ml.No drug-resistance mutation was identified by population-sequencing. Conversely, UDPS detected >1 drug-resistance mutation (rtA181T/A181V/rtM204I/rtA194T/rtT184A) in 13.6% of patients with an intra-patient prevalence ranging from 0.02% for rtA181V to 47.5% for rtA181T, both associated with suboptimal nucleotide-analogues (mostly adefovir) response. By UDPS analysis, 29.5% of patients carried >1 immune-escape mutation within the a-determinant (intra-patient prevalence from 0.84% to 100%). Although no patients received HBV-vaccination, sG145R (known to act as vaccine-escape) was detected in 2 patients with an intra-patient prevalence of 3.9% and 99.9%. Stop-codons were found in 15.9% patients (intra-patient prevalence range:1.6%-47.5%). They occurred at 5 HBsAg-positions including positions 172 and 182 known to correlate with an increased HBV oncogenic-potential.
Conclusions: A viral-quasispecies with reduced antigenicity, altered drug-susceptibility, and/or with enhanced oncogenic-potential characterizes a large fraction of AHB-patients. These viral-variants may potentially expose patients to severe and/or difficult-to-treat forms of HBV-infection, and may affect the efficacy of current HBV-vaccination strategy.
Marianna Aragri , University of Rome Tor Vergata , Rome , Italy
Assigned in sessions:
11.04.2014, 09:00-18:00, Poster, 7B - VIRAL HEPATITIS: HEPATITIS A, B, D E CLINICAL (EXCEPT THERAPY), Poster Exhibition
Copyright 1994-2016 MedHelp International. All rights reserved.
MedHelp is a division of Aptus Health.
This site complies with the HONcode standard for trustworthy health information.
The Content on this Site is presented in a summary fashion, and is intended to be used for educational and entertainment purposes only. It is not intended to be and should not be interpreted as medical advice or a diagnosis of any health or fitness problem, condition or disease; or a recommendation for a specific test, doctor, care provider, procedure, treatment plan, product, or course of action. Med Help International, Inc. is not a medical or healthcare provider and your use of this Site does not create a doctor / patient relationship. We disclaim all responsibility for the professional qualifications and licensing of, and services provided by, any physician or other health providers posting on or otherwise referred to on this Site and/or any Third Party Site. Never disregard the medical advice of your physician or health professional, or delay in seeking such advice, because of something you read on this Site. We offer this Site AS IS and without any warranties. By using this Site you agree to the following Terms and Conditions. If you think you may have a medical emergency, call your physician or 911 immediately.