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 - 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.
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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 -