mutations in acute hbv ultradeep sequence, only tenofovir looks very safe
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
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