TY - JOUR
T1 - Comparison of HBV RNA and Hepatitis B Core Related Antigen With Conventional HBV Markers Among Untreated Adults With Chronic Hepatitis B in North America
AU - Ghany, Marc G.
AU - King, Wendy C.
AU - Lisker-Melman, Mauricio
AU - Lok, Anna S.F.
AU - Terrault, Norah
AU - Janssen, Harry L.A.
AU - Khalili, Mandana
AU - Chung, Raymond T.
AU - Lee, William M.
AU - Lau, Daryl T.Y.
AU - Cloherty, Gavin A.
AU - Sterling, Richard K.
N1 - Funding Information:
This study was funded by Abbott Diagnostics as an ancillary study of the Hepatitis B Research Network to Dr. Richard K. Sterling.
Funding Information:
The authors acknowledge the use of HBRN samples and data as the sole contribution of the HBRN. The HBRN was funded as a Cooperative Agreement between the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) and the following investigators: Lewis R. Roberts, M.B., Ch.B., Ph.D. (U01‐DK082843); Anna Suk‐Fong Lok, M.D. (U01‐DK082863); Steven H. Belle, Ph.D., M.Sc.Hyg. (U01‐DK082864); Kyong‐Mi Chang, M.D. (U01‐DK082866); Michael W. Fried, M.D. (U01‐DK082867); Adrian M. Di Bisceglie, M.D. (U01‐DK082871); William M. Lee, M.D. (U01‐DK082872); Harry L.A. Janssen, M.D., Ph.D. (U01‐DK082874); Daryl T.‐Y. Lau, M.D., M.P.H. (U01‐DK082919); Richard K. Sterling, M.D., M.Sc. (U01‐DK082923); Steven‐Huy B. Han, M.D. (U01‐DK082927); Robert C. Carithers, M.D. (U01‐DK082943); Mandana Khalili, M.D. (U01‐DK082944); an interagency agreement with NIDDK: Lilia M. Ganova‐Raeva, Ph.D. (A‐DK‐3002‐001); and support from the intramural program, NIDDK, NIH: Marc G. Ghany, M.D., Intramural Research Program, NIDDK, NIH. Additional funding to support this study was provided to Kyong‐Mi Chang, M.D., 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, M.D., M.Sc. (UL1TR000058, NCATS (National Center for Advancing Translational Sciences, NIH), Mandana Khalili, M.D., M.A.S. (CTSA Grant Number UL1TR000004), Michael W. Fried, M.D. (CTSA Grant Number UL1TR001111), and Anna Suk‐Fong Lok (CTSA Grant Numbers UL1RR024986, U54TR001959). Additional support was provided by Gilead Sciences, Inc. and Roche Molecular Systems by a CRADA through the NIDDK. The authors also acknowledge the contributions of Jeffrey Gersch and Mark Anderson, Abbott Diagnostics, who performed the HBV RNA and HBcrAg testing.
Funding Information:
The authors acknowledge the use of HBRN samples and data as the sole contribution of the HBRN. The HBRN was funded as a Cooperative Agreement between the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) and the following investigators: Lewis R. Roberts, M.B., Ch.B., Ph.D. (U01-DK082843); Anna Suk-Fong Lok, M.D. (U01-DK082863); Steven H. Belle, Ph.D., M.Sc.Hyg. (U01-DK082864); Kyong-Mi Chang, M.D. (U01-DK082866); Michael W. Fried, M.D. (U01-DK082867); Adrian M. Di Bisceglie, M.D. (U01-DK082871); William M. Lee, M.D. (U01-DK082872); Harry L.A. Janssen, M.D., Ph.D. (U01-DK082874); Daryl T.-Y. Lau, M.D., M.P.H. (U01-DK082919); Richard K. Sterling, M.D., M.Sc. (U01-DK082923); Steven-Huy B. Han, M.D. (U01-DK082927); Robert C. Carithers, M.D. (U01-DK082943); Mandana Khalili, M.D. (U01-DK082944); an interagency agreement with NIDDK: Lilia M. Ganova-Raeva, Ph.D. (A-DK-3002-001); and support from the intramural program, NIDDK, NIH: Marc G. Ghany, M.D., Intramural Research Program, NIDDK, NIH. Additional funding to support this study was provided to Kyong-Mi Chang, M.D., 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, M.D., M.Sc. (UL1TR000058, NCATS (National Center for Advancing Translational Sciences, NIH), Mandana Khalili, M.D., M.A.S. (CTSA Grant Number UL1TR000004), Michael W. Fried, M.D. (CTSA Grant Number UL1TR001111), and Anna Suk-Fong Lok (CTSA Grant Numbers UL1RR024986, U54TR001959). Additional support was provided by Gilead Sciences, Inc. and Roche Molecular Systems by a CRADA through the NIDDK. The authors also acknowledge the contributions of Jeffrey Gersch and Mark Anderson, Abbott Diagnostics, who performed the HBV RNA and HBcrAg testing.
Funding Information:
Potential conflict of interest: Dr. Chung received grants from Gilead, AbbVie, Merck, Bristol‐Myers Squibb, Boehringer Ingelheim, Roche, Janssen, and GlaxoSmithKline. Dr. King received grants from AbbVie. Dr. Lisker‐Melman is on the speakers’ bureau for AbbVie and Gilead. Dr. Lok received grants from Bristol‐Myers Squibb, Gilead, and TARGET. Dr. Terrault consults for EXIGO, Entourage, and PPD Pharma. She received grants from Gilead, GlaxoSmithKline, and Roche‐Genentech. Dr. Janssen consults for and received grants from Arbutus, Gilead, Janssen, Merck, and Roche. He consults for Aligos, Arena, Eiger, Enyo, GlaxoSmithKline, Regulus, VBI Vaccines, Vir and Viroclinics. He received grants from AbbVie and Bristol‐Myers Squibb. Dr. Khalili consults for and received grants from Gilead. She received a grant from Intercept. Dr. Lee consults for Genentech, Karuna, Forma, SeaGen, and Cortexyme. He received grants from Merck, Gilead, Intercept, Celgene, Cumberland, Eiger, and Alexion. Dr. Lau consults for and received grants from Abbott. She advises for and received grants from Gilead. Dr. Cloherty is employed by and owns stock in Abbott. Dr. Sterling received grants from Abbott, Roche, AbbVie, and Gilead. He is on the data security monitoring board for Pfizer and AskBio. − + − + − − − + + −
Publisher Copyright:
© 2021 The Authors. Hepatology published by Wiley Periodicals LLC on behalf of American Association for the Study of Liver Diseases. This article has been contributed to by US Government employees and their work is in the public domain in the USA.
PY - 2021/11
Y1 - 2021/11
N2 - Background and Aims: The clinical utility of two biomarkers, hepatitis B virus (HBV) RNA and hepatitis B core-related antigen (HBcrAg), as compared to conventional markers of HBV replication and disease activity, is unclear. Approach and Results: Untreated participants in the North American Hepatitis B Research Network Adult Cohort Study were categorized by chronic hepatitis B (CHB) phases based on HBsAg and HBeAg status and HBV DNA and alanine aminotransferase (ALT) levels. HBV RNA and HBcrAg were measured (Abbott HBV pgRNA Research Assay and Fujirebio Lumipulse Immunoassay, respectively), and cross-sectional associations with conventional CHB markers were tested. Among 1,409 participants across all CHB phases, median HBV DNA was 3.8 log10 IU/mL and ALT was 34 U/L. HBV RNA was quantifiable in 99% of HBeAg+ and 58% of HBeAg− participants; HBcrAg was quantifiable in 20% of HBeAg+ (above linear range in the other 80%) and 51% of HBeAg− participants. Both markers differed across CHB phases (P < 0.001), with higher levels in the HBeAg+ and HBeAg− immune active phases. HBV RNA and HBcrAg correlated moderately strongly with HBV DNA in both HBeAg+ and HBeAg− phases (HBV RNA: e+ ρ = 0.84; e− ρ = 0.78; HBcrAg: e+ ρ = 0.66; e− ρ = 0.56; P for all, <0.001), but with HBsAg levels among HBeAg+ phases only (HBV RNA: e+ ρ = 0.71; P < 0.001; e− ρ = 0.18; P = 0.56; HBcrAg: e+ ρ = 0.51; P < 0.001; e− ρ = 0.27; P < 0.001). Associations of higher HBV RNA and HBcrAg levels with higher ALT, APRI, and Fibrosis-4 levels were consistent in HBeAg−, but not HBeAg+, phases. Conclusions: Despite clear relationships between HBV RNA and HBcrAg levels and CHB phases, these markers have limited additional value in differentiating CHB phases because of their strong association with HBV DNA and, to a lesser extent, with clinical disease indicators.
AB - Background and Aims: The clinical utility of two biomarkers, hepatitis B virus (HBV) RNA and hepatitis B core-related antigen (HBcrAg), as compared to conventional markers of HBV replication and disease activity, is unclear. Approach and Results: Untreated participants in the North American Hepatitis B Research Network Adult Cohort Study were categorized by chronic hepatitis B (CHB) phases based on HBsAg and HBeAg status and HBV DNA and alanine aminotransferase (ALT) levels. HBV RNA and HBcrAg were measured (Abbott HBV pgRNA Research Assay and Fujirebio Lumipulse Immunoassay, respectively), and cross-sectional associations with conventional CHB markers were tested. Among 1,409 participants across all CHB phases, median HBV DNA was 3.8 log10 IU/mL and ALT was 34 U/L. HBV RNA was quantifiable in 99% of HBeAg+ and 58% of HBeAg− participants; HBcrAg was quantifiable in 20% of HBeAg+ (above linear range in the other 80%) and 51% of HBeAg− participants. Both markers differed across CHB phases (P < 0.001), with higher levels in the HBeAg+ and HBeAg− immune active phases. HBV RNA and HBcrAg correlated moderately strongly with HBV DNA in both HBeAg+ and HBeAg− phases (HBV RNA: e+ ρ = 0.84; e− ρ = 0.78; HBcrAg: e+ ρ = 0.66; e− ρ = 0.56; P for all, <0.001), but with HBsAg levels among HBeAg+ phases only (HBV RNA: e+ ρ = 0.71; P < 0.001; e− ρ = 0.18; P = 0.56; HBcrAg: e+ ρ = 0.51; P < 0.001; e− ρ = 0.27; P < 0.001). Associations of higher HBV RNA and HBcrAg levels with higher ALT, APRI, and Fibrosis-4 levels were consistent in HBeAg−, but not HBeAg+, phases. Conclusions: Despite clear relationships between HBV RNA and HBcrAg levels and CHB phases, these markers have limited additional value in differentiating CHB phases because of their strong association with HBV DNA and, to a lesser extent, with clinical disease indicators.
UR - http://www.scopus.com/inward/record.url?scp=85114481798&partnerID=8YFLogxK
U2 - 10.1002/hep.32018
DO - 10.1002/hep.32018
M3 - Article
C2 - 34133774
AN - SCOPUS:85114481798
SN - 0270-9139
VL - 74
SP - 2395
EP - 2409
JO - Hepatology
JF - Hepatology
IS - 5
ER -