Prevalence of hepatitis B antiviral drug resistance variants in North American patients with chronic hepatitis B not receiving antiviral treatment

J Viral Hepat. 2017 Nov;24(11):1032-1042. doi: 10.1111/jvh.12732. Epub 2017 Jul 3.

Abstract

Antiviral drug resistance hepatitis B virus (HBV) variants (HBV-DR) occur spontaneously in chronic hepatitis B (CHB) patients and after exposure to nucleos(t)ide analogues (NUCs). We determined the prevalence of HBV-DR variants among participants of the Hepatitis B Research Network (HBRN) Cohort Study conducted at 21 sites in the United States (US) and Canada. Samples obtained from 1342 CHB participants aged ≥18 years, and who were currently not receiving NUCs, were tested for HBV-DR variants by Sanger sequencing. In addition, next generation sequencing (NGS) was used to characterize HBV-DR variants from 66 participants with and 66 participants with no prior NUC exposure matched for HBV genotype and HBV DNA level. Half the participants were men, 75% Asian, 26% HBeAg positive. Primary HBV-DR variants were detected by Sanger sequencing in 16 (1.2%) participants: 2/142 (1.4%) with and 14/1200 (1.2%) without prior NUC exposure; only 1 of these 16 had a secondary variant. In total, 23 (1.7%) participants had secondary variants, including 1 with prior NUC experience. In the subset of 132 participants, NGS detected HBV-DR variants in a higher proportion of participants: primary variants in 18 (13.6%) (8 [12.1%] with, and 10 [15.2%] without prior NUC therapy) and secondary variants in 10 (7.6%) participants. Based on Sanger sequencing, prevalence of primary HBV-DR variants is low (1.2%) among adults with CHB in US/Canada. The similar low prevalence of HBV-DR variants in participants with and without NUC treatment suggests transmission of these variants is uncommon.

Keywords: Sanger sequencing; antiviral treatment; hepatitis B virus; next generation sequencing; nucleos(t)ide analogues.

Publication types

  • Multicenter Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Antiviral Agents / pharmacology*
  • Antiviral Agents / therapeutic use
  • DNA, Viral
  • Drug Resistance, Viral*
  • Female
  • Genetic Variation
  • Genotype
  • Hepatitis B virus / drug effects*
  • Hepatitis B virus / genetics
  • Hepatitis B, Chronic / diagnosis
  • Hepatitis B, Chronic / drug therapy
  • Hepatitis B, Chronic / epidemiology*
  • Hepatitis B, Chronic / virology
  • High-Throughput Nucleotide Sequencing
  • Humans
  • Male
  • Middle Aged
  • Mutation
  • North America / epidemiology
  • Population Surveillance
  • Prevalence
  • Sequence Analysis, DNA
  • Young Adult

Substances

  • Antiviral Agents
  • DNA, Viral

Associated data

  • GENBANK/DK082863
  • GENBANK/DK082864
  • GENBANK/DK082866
  • GENBANK/DK082867
  • GENBANK/DK082871
  • GENBANK/DK082872
  • GENBANK/DK082874
  • GENBANK/DK082919
  • GENBANK/DK082923
  • GENBANK/DK082927
  • GENBANK/DK082943
  • GENBANK/DK082944