Novel Biomarkers of Hepatitis B Virus and Their Use in Chronic Hepatitis B Patient Management

Abstract

Even though an approved vaccine for hepatitis B virus (HBV) is available and widely used, over 257 million individuals worldwide are living with chronic hepatitis B (CHB) who require monitoring of treatment response, viral activity, and disease progression to reduce their risk of HBV-related liver disease. There is currently a lack of predictive markers to guide clinical management and to allow treatment cessation with reduced risk of viral reactivation. Novel HBV biomarkers are in development in an effort to improve the management of people living with CHB, to predict disease outcomes of CHB, and further understand the natural history of HBV. This review focuses on novel HBV biomarkers and their use in the clinical setting, including the description of and methodology for quantification of serum HBV RNA, hepatitis B core-related antigen (HBcrAg), quantitative hepatitis B surface antigen (qHBsAg), including ultrasensitive HBsAg detection, quantitative anti-hepatitis B core antigen (qAHBc), and detection of HBV nucleic acid-related antigen (HBV-NRAg). The utility of these biomarkers in treatment-naïve and treated CHB patients in several clinical situations is further discussed. Novel HBV biomarkers have been observed to provide critical clinical information and show promise for improving patient management and our understanding of the natural history of HBV.

Hepatitis B seroconversion revisited: new insights into the natural history of acute hepatitis B virus (HBV) infection from quantitative and highly sensitive assays and novel biomarkers

“…Recent studies have shown that HBV RNA is detectable in the serum of chronic hepatitis B patients (treated and untreated) as well as in acute infection [ 12 , 13 ]. The HBV RNA in serum includes primarily full-length encapsidated pgRNA.…”

“…Serum HBV pgRNA has emerged as a new biomarker reflecting the levels and activity of intrahepatic HBV covalently closed circular DNA (cccDNA) [ 13 ]. HBV pgRNA can be released into the serum within enveloped virions.…”

“…HBeAg is the predominant component detected by the HBcrAg assay in HBeAg positive sera. HBcrAg has been shown to correlate with HBV cccDNA and has been extensively studied relative to the phases of chronic hepatitis B infection and in monitoring antiviral therapies [ 13 , 18 ]. In the current study of acute hepatitis B, HBcrAg kinetics were similar to HBeAg and HBV DNA and HBcrAg correlated with both markers.…”

Performance of the cobas® HBV RNA Automated Investigational Assay for the Detection and Quantification of Circulating HBV RNA in Chronic HBV Patients

“…for nucleic acid amplification and detection) likely contribute to variability in quantitative molecular test results, which can be up to 100-fold using various WHO international standards [24][25][26]. The availability of an international standard is mandatory to properly compare results obtained from different studies [6,7,25]. The establishment of such a standard would enable a better interpretation of results generated with tests targeting different parts of the HBV genome.…”

Blood-Based Biomarkers in Hepatitis B Virus-Related Hepatocellular Carcinoma, Including the Viral Genome and Glycosylated Proteins

“…Recently, new biomarkers for liver diseases, based on post-translational modifications by glycosylation, have been attracting attention. In addition to tumor markers for HCC, the HBV genotype, HBV genomic mutations, host genome mutations in HBV-infected hepatocytes and gene expression patterns of HCC cells could be candidate biomarkers for HBV-related HCC [ 5 , 6 , 7 ]. Novel technologies including these biomarkers have the potential to predict the prognosis of HCC patients.…”