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.
| Original language | English |
|---|---|
| Pages (from-to) | 1032-1042 |
| Number of pages | 11 |
| Journal | Journal of Viral Hepatitis |
| Volume | 24 |
| Issue number | 11 |
| DOIs | |
| State | Published - Nov 2017 |
Keywords
- Sanger sequencing
- antiviral treatment
- hepatitis B virus
- next generation sequencing
- nucleos(t)ide analogues
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Prevalence of hepatitis B antiviral drug resistance variants in North American patients with chronic hepatitis B not receiving antiviral treatment. / the Hepatitis B Research Network (HBRN).
In: Journal of Viral Hepatitis, Vol. 24, No. 11, 11.2017, p. 1032-1042.Research output: Contribution to journal › Article › peer-review
TY - JOUR
T1 - Prevalence of hepatitis B antiviral drug resistance variants in North American patients with chronic hepatitis B not receiving antiviral treatment
AU - the Hepatitis B Research Network (HBRN)
AU - Lok, A. S.
AU - Ganova-Raeva, L.
AU - Cloonan, Y.
AU - Punkova, L.
AU - Lin, H. H.S.
AU - Lee, W. M.
AU - Ghany, M. G.
AU - Lau, Daryl T.Y.
AU - Chung, Raymond T.
AU - Roberts, Lewis R.
AU - Smith, Coleman I.
AU - Di Bisceglie, Adrian M.
AU - Melman, Mauricio
AU - Janssen, L. A.
AU - Wong, David K.
AU - Juan, Joshua
AU - Feld, Jordan
AU - Yim, Colina
AU - Heathcote, Jenny
AU - Perrillo, Robert
AU - Do, Son
AU - Han, Steven Huy B.
AU - Tran, Tram T.
AU - Terrault, Norah A.
AU - Khalili, Mandana
AU - Cooper, Stewart L.
AU - Fontana, Robert J.
AU - Tsai, Naoky
AU - Fried, Michael W.
AU - Patel, Keyur
AU - Evon, Donna
AU - Carithers, Robert C.
AU - Shuhart, Margaret
AU - Kowdley, Kris V.
AU - Wang, Chia C.
AU - Sterling, Richard K.
AU - Jake Liang, T.
AU - Hoofnagle, Jay H.
AU - Doo, Edward
AU - Chang, Kyong Mi
AU - Park, Jang June
AU - Belle, Steven H.
AU - Wahed, Abdus
AU - Kleiner, David
N1 - Funding Information: Norah A. Terrault, MD, MPH (CTSA Grant Number UL1TR000004), Michael W. Fried, MD (CTSA Grant Number UL1TR001111), and Anna Suk-Fong Lok (CTSA Grant Number UL1RR024986.) Additional support was provided by Gilead Sciences, Inc. and Roche Molecular Systems via a CRADA through the NIDDK. Funding Information: The HBRN was funded by a U01 grant from the National Institute of Diabetes and Digestive and Kidney Diseases to the following investigators Lewis R. Roberts, MB, ChB, PhD (DK 082843), Anna Suk-Fong Lok, MD (DK082863), Steven H. Belle, PhD, MScHyg (DK082864), Kyong-Mi Chang, MD (DK082866), Michael W. Fried, MD (DK082867), Adrian M. Di Bisceglie, MD (DK082871), William M. Lee, MD (DK082872), Harry L. A. Janssen, MD, PhD (DK082874), Daryl T-Y Lau, MD, MPH (DK082919), Richard K. Sterling, MD, MSc (DK082923), Steven-Huy B. Han, MD (DK082927), Robert C. Carithers, MD (DK082943), Norah A. Terrault, MD, MPH (DK082944), an interagency agreement with NIDDK: Lilia M. Ganova-Raeva, PhD (A-DK-3002-001) and support from the intramural program, NIDDK, NIH: Marc G. Ghany, MD. Additional funding to support this study was provided to Kyong-Mi Chang, MD, the Immunology Center, (NIH/NIDDK Center of Molecular Studies in Digestive and Liver Diseases P30DK50306, NIH Public Health Service Research Grant M01-RR00040), Richard K. Sterling, MD, MSc (UL1TR000058, NCATS (National Center for Advancing Translational Sciences, NIH), Funding Information: ASL has received research grants from Bristol-Myers Squibb and Gilead. WML has received research grants from Bristol-Myers Squibb and Gilead. LGR, YKC, LP and HSL have no conflict to declare. The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention. Funding Information: Funding information The HBRN was funded by a U01 grant from the National Institute of Diabetes and Digestive and Kidney Diseases to the following investigators Lewis R. Roberts, MB, ChB, PhD (DK 082843), Anna Suk-Fong Lok, MD (DK082863), Steven H. Belle, PhD, MScHyg (DK082864), Kyong-Mi Chang, MD (DK082866), Michael W. Fried, MD (DK082867), Adrian M. Di Bisceglie, MD (DK082871), William M. Lee, MD (DK082872), Harry L. A. Janssen, MD, PhD (DK082874), Daryl T-Y Lau, MD, MPH (DK082919), Richard K. Sterling, MD, MSc (DK082923), Steven-Huy B. Han, MD (DK082927), Robert C. Carithers, MD (DK082943), Norah A. Terrault, MD, MPH (DK082944), an interagency agreement with NIDDK: Lilia M. Ganova-Raeva, PhD (A-DK-3002-001) and support from the intramural program, NIDDK, NIH: Marc G. Ghany, MD. Additional funding to support this study was provided to Kyong-Mi Chang, MD, the Immunology Center, (NIH/NIDDK Center of Molecular Studies in Digestive and Liver Diseases P30DK50306, NIH Public Health Service Research Grant M01-RR00040), Richard K. Sterling, MD, MSc (UL1TR000058, NCATS (National Center for Advancing Translational Sciences, NIH), Norah A. Terrault, MD, MPH (CTSA Grant Number UL1TR000004), Michael W. Fried, MD (CTSA Grant Number UL1TR001111), and Anna Suk-Fong Lok (CTSA Grant Number UL1RR024986.) Additional support was provided by Gilead Sciences, Inc. and Roche Molecular Systems via a CRADA through the NIDDK. In addition to the authors, the HBRN would like to acknowledge the contributions of the following: Harvard Consortium: Nezam Afdhal, MD, Asad Javaid, MBBS, Jianghe Niu, Johanna Han, Imad Nasser, MD (Beth Israel Deaconess Medical Center, Boston, MA, USA). Minnesota Alliance for Research in Chronic Hepatitis B: Alisha C. Stahler, Linda Stadheim, RN (Mayo Clinic Rochester, Rochester, MN, USA), Mohamed Hassan, MD (University of Minnesota, Minneapolis, MN, USA). Midwest Hepatitis B Consortium: Kathryn Rushing, RN, Rosemary A. Nagy, RDN, LD, MBA, Jacki Cerkoski, RN, MSN (Saint Louis University School of Medicine, St Louis, MO, USA), Debra DeMarco Shaw, RN, BSN, Lisa Kessels, RN, Michael K. Klebert, PhD, RN, ANP-BC (Washington University, St. Louis, MO, USA). University of Toronto Consortium: Seham Noureldin, PhD, Danie La, RN, Lucie Liu, MSc, CCRP, Diana Kaznowski, RN, Jiayun Chen, Doinita Vladutu, Orlando Cerocchi (Toronto Western & General Hospitals, Toronto, Ontario). HBV CRN North Texas Consortium: Stacey Minshall, RN, BSN (Division of Digestive and Liver Diseases, University of Texas Southwestern Medical Center at Dallas, Dallas, Texas), Sheila Bass (University of Texas Southwestern, Dallas, TX, USA), Ethel Sauceda, BS (Baylor University Medical Center, Dallas, TX, USA). Los Angeles Hepatitis B Consortium: Samuel French, MD, Velma Peacock, RN (David Geffen School of Med, UCLA, Los Angeles, CA, USA). San Francisco Hepatitis B Research Group Consortium: Ashley Ungermann, MS, Claudia Ayala, MS, Emma Olson, BS, Ivy Lau, BS (University of California-San Francisco), Veronika Podolskaya, BS, NCPT, Nata DeVole, RN (California Pacific Medical Center, Research Institute). Michigan Hawaii Consortium: Barbara McKenna, MD, Kelly Oberhelman, PAC, Sravanthi Kaza, Bpharm, Cassandra Rodd, BS (University of Michigan, Ann Arbor, MI, USA), Leslie Huddleston, NP, Peter Poerzgen, PhD (The Queen's Medical Center, University of Hawaii, Honolulu, HI). Chapel Hill, NC Consortium: Jama M. Darling, M.D., A. Sidney Barritt, M.D., Tiffany Marsh, BA, Vikki Metheny, ANP, Danielle Cardona, PA-C (University of North Carolina at Chapel Hill, Chapel Hill, NC, USA). Virginia Commonwealth University Medical Center: Velimir A. Luketic, MD, Paula G Smith, RN, BSN, Charlotte Hofmann, RN (Virginia Commonwealth University Health System, Richmond, VA, USA). PNW/Alaska Clinical Center Consortium: Alycia Wolfstone, RN, MN (University of Washington Medical Center, Seattle, WA, USA) Jody Mooney, Lupita Cardona-Gonzalez (Virginia Mason Medical Center, Seattle, WA, USA). Liver Diseases Branch, NIDDK, NIH: Nancy Fryzek, RN, BSN, Elenita Rivera, BSN, Nevitt Morris, Vanessa Haynes-Williams. Liver Disease Research Branch, NIDDK, NIH: Averell H. Sherker, MD, Rebecca J. Torrance, RN, MS, Sherry R. Hall, MS. Immunology Center: Mary E. Valiga, RN, Keith Torrey, BS, Danielle Levine, BS, James Keith, BS, Michael Betts, PhD (University of Pennsylvania, Philadelphia, PA, USA), Luis J. Montaner, DVM, DPhil (Wistar Institute, Philadelphia, PA, USA). Data Coordinating Center: Michelle Danielson, PhD, Tamara Haller, Geoffrey Johnson, MS, Stephanie Kelley, MS, Sharon Lawlor, MBA, Joan M. MacGregor, MS, Andrew Pelesko, BS, Donna Stoliker, Ella Zadorozny, MS (Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA, USA). Publisher Copyright: © 2017 John Wiley & Sons Ltd
PY - 2017/11
Y1 - 2017/11
N2 - 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.
AB - 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.
KW - Sanger sequencing
KW - antiviral treatment
KW - hepatitis B virus
KW - next generation sequencing
KW - nucleos(t)ide analogues
UR - http://www.scopus.com/inward/record.url?scp=85021729548&partnerID=8YFLogxK
U2 - 10.1111/jvh.12732
DO - 10.1111/jvh.12732
M3 - Article
C2 - 28581155
AN - SCOPUS:85021729548
SN - 1352-0504
VL - 24
SP - 1032
EP - 1042
JO - Journal of Viral Hepatitis
JF - Journal of Viral Hepatitis
IS - 11
ER -