Abstract

Viral biomarkers are important tools for monitoring chronic hepatitis B virus (HBV) hepatitis B early antigen (HBeAg) negative infection, both in its natural course as well as during and after treatment. The biomarkers consist of antibodies against viral epitopes, viral proteins, and molecular surrogate markers of the quantity and transcriptional activity of the stable episomal HBV covalently closed circular DNA (cccDNA) which is located in the nuclei of the infected hepatocytes. HBV deoxyribonucleic acid (DNA) or else viral load measurement in plasma or serum is a marker of HBV replication of major clinical importance. HBV DNA is used for staging and treatment monitoring as described in international scientific guidelines. Quantification of HBV antigens, mainly hepatitis B surface antigen (HBsAg) as well as Hepatitis B core related antigen (HBcrAg), play an important yet secondary role, especially in cases of low or undetectable HBV DNA and has been evaluated for the classification of the inactive carrier state, as a predictor of subsequent HBsAg clearance, treatment outcome, and development of hepatocellular carcinoma (HCC). The measurement of the replicative intermediate HBV RNA in serum is currently evaluated and may also prove to be a significant biomarker particularly in patients treated with nucleot(s)ide analogs. This review focuses on the viral biomarkers mentioned above and their role in HBV, HBeAg negative, infection.

Highlights

  • Chronic liver inflammation, or chronic hepatitis, is a common disease and a worldwide public health issue

  • This review focuses on the viral biomarkers mentioned above and their role in hepatitis B virus (HBV), hepatitis B early antigen (HBeAg) negative, infection

  • A number of different experimental methods for the quantification of intrahepatic and serum HBV RNA are utilized based on quantitative real-time RT polymerase chain reaction (PCR) assays, there is no consensus on a single technique and commercial available assay for the detection of HBV RNA

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Summary

Introduction

Chronic hepatitis, is a common disease and a worldwide public health issue. The first one is serology, a term comprising the detection and quantification of viral antigens and viral specific antibodies and the second is nucleic acid testing (NAT) for the detection and quantification of HBV genome and its RNA transcripts [2] (Figure 1) Both serology and NAT are in routine use, for the diagnosis of chronic and acute HBV infection, and for monitoring chronic HBV infection with or without treatment. Serological and molecular biomarkers are used for the identification of the HBeAg negative inactive carrier (IC) state, for treatment initiation and monitoring, and as predictors of HBV and liver related events [3,4].

Antigen and Antibody Detection
Hepatitis B Surface Antigen Quantification
Hepatitis B Early Antigen Quantification
Hepatitis B Core Related Antigen Quantification
Hepatitis B Virus Deoxyribonucleic Acid
Hepatitis B Virus Genotype
Hepatitis B Virus Ribonucleic Acid
Biomarkers for the Identification of the Inactive Carrier State
Biomarkers for the Prediction of Spontaneous HBsAg Clearance
Treatment Monitoring
Predictive Biomarkers for the Response to Pegylated-Interferon
Hepatocellular Carcinoma
Future Therapies and Viral Biomarkers
Findings
Conclusions
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