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Publication Information
Affiliation
1Liver Diseases Branch, NIDDK, NIH, Bethesda, MD.
2Graduate School of Public Health University of Pittsburgh, Pittsburgh, PA.
3Washington University School of Medicine and John Cochran VA Medical Center, St. Louis, MO.
4Division of Gastroenterology and Hepatology, University of Michigan, Ann Arbor, MI.
5Division of Gastrointestinal and Liver Diseases, Keck Medicine of University of Southern California, Los Angeles, CA.
6Toronto Centre for Liver Disease, University of Toronto, Toronto, ON, Canada.
7Division of Gastroenterology and Hepatology, Department of Medicine, University of California San Francisco, San Francisco, CA.
8Hepatology and Liver Center, Massachusetts General Hospital, Boston, MA.
9Meredith Mosle Chair in Liver Disease, UT Southwestern Medical Center, Dallas, TX.
10Division of Gastroenterology and Hepatology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA.
11Abbott Diagnostics, Abbott Park, IL.
12Division of Gastroenterology, Hepatology, and Nutrition, Virginia Commonwealth University, Richmond, VA.
Authors
Chung RT, Cloherty GA, Ghany MG, Janssen HLA, Khalili M, King WC, Lau DTY, Lee WM, Lisker-Melman M, Lok ASF, Sterling RK, Terrault N
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 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+ ? = 0.84; e- ? = 0.78; HBcrAg: e+ ? = 0.66; e- ? = 0.56; P for all, <0.001), but with HBsAg levels among HBeAg+ phases only (HBV RNA: e+ ? = 0.71; P < 0.001; e- ? = 0.18; P = 0.56; HBcrAg: e+ ? = 0.51; P < 0.001; e- ? = 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.