Table 2.
Description of Virological and Serological Markers of Acute and Chronic HBV: Their Role and Use in Diagnosis.
| Serum Biomarker | Description/Source | Role | Predictor/Outcome |
|---|---|---|---|
| HBsAg (essential) | Surface/envelope protein derived from cccDNA and/or integrated DNA | Required for infectivity, excessive quantities may inhibit immune response |
Initial diagnosis of: acute HB—transient HBs antigenemia; CHB—persistent HBs antigenemia (>6 months) Loss/seroconversion results in functional cure, quantification is used to monitor therapeutic outcomes |
| HBV DNA (essential) | Found in infectious virions | Required for replication | Used to monitor therapy and assess risk to pregnant women to avoid perinatal transmission; HBV DNA >2000 IU/mL is a key predictor of HCC risk |
| HBeAg (essential) | Secreted nonstructural protein derived from precore | Tolerogenicity, immune regulation, persistence | Defines phase CHB; seroconversion is one of the main therapeutic endpoints; quantification is used to predict seroconversion and therapeutic response |
| HBcrAg (investigational) | Composed of viral HBcAg, HBeAg, and p22cr | Combines both structural and nonstructural proteins forming empty capsids and virions | Monitoring therapy and predictor of: treatment response; HBeAg seroconversion and HBV reactivation in occult infection during immunosuppression; and risk for HCC5 |
| HBV pgRNA (investigational) | Derived directly from the TA of intrahepatic cccDNA/minichromosome | Transcriptional template for Pol protein production and HBV replication | Assesses intrahepatic cccDNA activity, used for monitoring current and novel therapies particularly when HBV DNA is suppressed, predictor of HBeAg seroconversion6 |
| Anti‐HBc (optional) | Reliable marker of host response to HBV exposure | Immune response to HBcAg | Indication of HBV exposure, especially useful in diagnosis of occult infection |
| Anti‐HBs (optional) | Host response to hepatitis B vaccination and/or after decline/loss of HBsAg | Immune response to HBsAg | Presence confirms efficacy of vaccination or achievement of functional cure in CHB |
| dlDNA (future) | Genomic form of DNA | Involved in integration | May have the potential to reflect intrahepatic activity and in particular risk for HCC11 |
| spDNA/RNA (investigational/future) | Truncated variants arising from spDNA/RNA during replication | May be involved in liver disease, including HCC, and impaired response to interferon | PCR assays for detection of spDNA/RNA may reflect increased risk for HCC10 |