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

摘要

Summary 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 ( NUC s). 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 NUC s, 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% HB eAg 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.