Acute hepatitis B infection associated with drug-resistant hepatitis B virus

J Clin Virol. 2010 Aug;48(4):270-4. doi: 10.1016/j.jcv.2010.05.010. Epub 2010 Jun 26.

Abstract

Background: Pre-existing antiviral-resistant hepatitis B virus (HBV) has been associated with primary non-response to lamivudine treatment in patients with chronic hepatitis B, but little is known of the capacity for resistant HBV to cause primary infection.

Objective: The study was to investigate if Beijing patients with acute hepatitis B (AHB) are infected with drug-resistant HBV.

Study design: Sera were collected from 201 NA-untreated patients with AHB. Direct polymerase chain reaction (PCR) sequencing was used to screen HBV reverse-transcriptase (RT) domain and clonal sequencing were performed for all resistance-positive samples.

Results: Direct PCR sequencing showed that 14 samples (7.0%) were positive for drug-resistant HBV variants, comprised of 11 with the lamivudine-resistant pattern rtM204I and/or rtM204V in the presence and absence of compensatory mutations rtL80I, rtV173L, and rtL180M; two with the adefovir-resistant pattern rtA181V; and one with the entecavir-resistant pattern rtL180M+rtS202G+rtM204V. Concomitance of resistance variants with wild-type HBV was observed in samples from 13 patients. Clonal sequencing verified direct sequencing results. Furthermore, variants associated with resistance to adefovir or entecavir were found in 3 samples.

Conclusions: Drug-resistant HBV strains, including those not resistant to lamivudine, are transmissible and can cause acute hepatitis B in China.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenine / analogs & derivatives
  • Adenine / pharmacology
  • Adult
  • Amino Acid Substitution / genetics
  • Antiviral Agents / pharmacology*
  • China
  • DNA, Viral / chemistry
  • DNA, Viral / genetics
  • Drug Resistance, Viral*
  • Guanine / analogs & derivatives
  • Guanine / pharmacology
  • Hepatitis B / virology*
  • Hepatitis B virus / drug effects*
  • Hepatitis B virus / isolation & purification*
  • Humans
  • Lamivudine / pharmacology
  • Male
  • Middle Aged
  • Molecular Sequence Data
  • Mutation, Missense*
  • Organophosphonates / pharmacology
  • Polymerase Chain Reaction
  • RNA-Directed DNA Polymerase / genetics
  • Sequence Analysis, DNA
  • Viral Proteins / genetics

Substances

  • Antiviral Agents
  • DNA, Viral
  • Organophosphonates
  • Viral Proteins
  • Lamivudine
  • entecavir
  • Guanine
  • adefovir
  • RNA-Directed DNA Polymerase
  • Adenine

Associated data

  • GENBANK/GQ377514
  • GENBANK/GQ377515
  • GENBANK/GQ377516
  • GENBANK/GQ377517
  • GENBANK/GQ377518
  • GENBANK/GQ377519
  • GENBANK/GQ377520
  • GENBANK/GQ377521
  • GENBANK/GQ377522
  • GENBANK/GQ377523
  • GENBANK/GQ377524
  • GENBANK/GQ377525
  • GENBANK/GQ377526
  • GENBANK/GQ377527
  • GENBANK/GQ377528
  • GENBANK/GQ377529
  • GENBANK/GQ377530
  • GENBANK/GQ377531
  • GENBANK/GQ377532
  • GENBANK/GQ377533
  • GENBANK/GQ377534
  • GENBANK/GQ377535
  • GENBANK/GQ377536
  • GENBANK/GQ377537
  • GENBANK/GQ377538
  • GENBANK/GQ377539
  • GENBANK/GQ377540
  • GENBANK/GQ377541
  • GENBANK/GQ377542
  • GENBANK/GQ377543
  • GENBANK/GQ377544
  • GENBANK/GQ377545
  • GENBANK/GQ377546
  • GENBANK/GQ377547
  • GENBANK/GQ377548
  • GENBANK/GQ377549
  • GENBANK/GQ377550
  • GENBANK/GQ377551
  • GENBANK/GQ377552
  • GENBANK/GQ377553
  • GENBANK/GQ377554
  • GENBANK/GQ377555
  • GENBANK/GQ377556
  • GENBANK/GQ377557
  • GENBANK/GQ377558
  • GENBANK/GQ377559
  • GENBANK/GQ377560
  • GENBANK/GQ377561
  • GENBANK/GQ377562
  • GENBANK/GQ377563
  • GENBANK/GQ377564
  • GENBANK/GQ377565
  • GENBANK/GQ377566
  • GENBANK/GQ377567
  • GENBANK/GQ377568
  • GENBANK/GQ377569
  • GENBANK/GQ377570
  • GENBANK/GQ377571
  • GENBANK/GQ377572
  • GENBANK/GQ377573
  • GENBANK/GQ377574
  • GENBANK/GQ377575
  • GENBANK/GQ377576
  • GENBANK/GQ377577
  • GENBANK/GQ377578
  • GENBANK/GQ377579
  • GENBANK/GQ377580
  • GENBANK/GQ377581
  • GENBANK/GQ377582
  • GENBANK/GQ377583
  • GENBANK/GQ377584
  • GENBANK/GQ377585
  • GENBANK/GQ377586
  • GENBANK/GQ377587
  • GENBANK/GQ377588
  • GENBANK/GQ377589
  • GENBANK/GQ377590
  • GENBANK/GQ377591
  • GENBANK/GQ377592
  • GENBANK/GQ377593
  • GENBANK/GQ377594
  • GENBANK/GQ377595
  • GENBANK/GQ377596
  • GENBANK/GQ377597
  • GENBANK/GQ377598
  • GENBANK/GQ377599
  • GENBANK/GQ377600
  • GENBANK/GQ377601
  • GENBANK/GQ377602
  • GENBANK/GQ377603
  • GENBANK/GQ377604
  • GENBANK/GQ377605
  • GENBANK/GQ377606
  • GENBANK/GQ377607
  • GENBANK/GQ377608
  • GENBANK/GQ377609
  • GENBANK/GQ377610
  • GENBANK/GQ377611
  • GENBANK/GQ377612
  • GENBANK/GQ377613
  • GENBANK/GQ377614
  • GENBANK/GQ377615
  • GENBANK/GQ377616
  • GENBANK/GQ377617
  • GENBANK/GQ377618
  • GENBANK/GQ377619
  • GENBANK/GQ377620
  • GENBANK/GQ377621
  • GENBANK/GQ377622
  • GENBANK/GQ377623
  • GENBANK/GQ377624
  • GENBANK/GQ377625
  • GENBANK/GQ377626
  • GENBANK/GQ377627
  • GENBANK/GQ377628
  • GENBANK/GQ377629
  • GENBANK/GQ377630
  • GENBANK/GQ377631
  • GENBANK/GQ377632
  • GENBANK/GQ377633
  • GENBANK/GQ377634
  • GENBANK/GQ377635
  • GENBANK/GQ377636
  • GENBANK/GQ377637
  • GENBANK/GQ377638
  • GENBANK/GQ377639
  • GENBANK/GQ377640
  • GENBANK/GQ377641
  • GENBANK/GQ377642
  • GENBANK/GQ377643
  • GENBANK/GQ377644