Comparison of HBV RNA and Hepatitis B Core Related Antigen With Conventional HBV Markers Among Untreated Adults With Chronic Hepatitis B in North America.

Marc G Ghany, Wendy C King, Mauricio Lisker-Melman, Anna S F Lok, Norah Terrault, Harry L A Janssen, Mandana Khalili, Raymond T Chung, William M Lee, Daryl T Y Lau, Gavin A Cloherty, Richard K Sterling

Journal: Hepatology (Baltimore, Md.) 2022;74(5):2395-2409

PMID: 34133774

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Abstract

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 log 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.

© 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.

Address: Liver Diseases Branch, NIDDK, NIH, Bethesda, MD.; Graduate School of Public Health University of Pittsburgh, Pittsburgh, PA.; Washington University School of Medicine and John Cochran VA Medical Center, St. Louis, MO.; Division of Gastroenterology and Hepatology, University of Michigan, Ann Arbor, MI.; Division of Gastrointestinal and Liver Diseases, Keck Medicine of University of Southern California, Los Angeles, CA.; Toronto Centre for Liver Disease, University of Toronto, Toronto, ON, Canada.; Division of Gastroenterology and Hepatology, Department of Medicine, University of California San Francisco, San Francisco, CA.; Hepatology and Liver Center, Massachusetts General Hospital, Boston, MA.; Meredith Mosle Chair in Liver Disease, UT Southwestern Medical Center, Dallas, TX.; Division of Gastroenterology and Hepatology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA.; Abbott Diagnostics, Abbott Park, IL.; Division of Gastroenterology, Hepatology, and Nutrition, Virginia Commonwealth University, Richmond, VA.

DOI: 10.1002/hep.32018

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MeSH Terms: Adult, Alanine Transaminase, Biomarkers, Cross-Sectional Studies, DNA, Viral, Female, Follow-Up Studies, Genotype, Hepatitis B Core Antigens, Hepatitis B Surface Antigens, Hepatitis B e Antigens, Hepatitis B virus, Hepatitis B, Chronic, Humans, Male, Middle Aged, North America, RNA, Viral