Phase-Dependent Interpretation of Quantitative Hepatitis B Surface Antigen and Hepatocellular Carcinoma Risk in Chronic Hepatitis B Infection

Document Type

Article

Publication Date

6-27-2026

Publication Title

World J Hepatol

Abstract

Quantitative hepatitis B surface antigen (qHBsAg) is one of the known and commonly utilized blood tests that shows the total hepatitis B virus (HBV) antigen production from 2 distinct sources: (1) Transcriptionally active covalently closed circular DNA; and (2) The HBV DNA that is already integrated to the host genome. Its use has resulted in inconsistent results across patients with different stages of hepatitis B and therefore has limited its clinical utility. For this reason, this marker is yet to be adopted on a larger scale for routine hepatocellular carcinoma (HCC) cancer prediction. Emerging evidence suggests that the prognostic meaning of qHBsAg is heavily impacted by the phase of HBV infection and the underlying source of the antigen presence. For instance, in patients with hepatitis B e antigen+ chronic infection, elevated qHBsAg levels do indicate a state of active covalently closed circular DNA transcription and active viral replication, and higher HBsAg levels (> 10000 IU/mL) are paradoxically associated with delayed HCC development. In contrast, in patients with negative hepatitis B e antigen and a low viral load (< 2000 IU/mL), high qHBsAg (> 1000 IU/mL) suggests replication-independent HBsAg production from the integrated HBV DNA and is strongly associated with increased risk of HCC with an adjusted hazard ratio of 13.7 (95%CI: 4.8-39.3). This minireview analyzes the current data and presents a phase-dependent framework for interpreting qHBsAg in untreated chronic hepatitis B virus patients. We also discuss how it can be used in clinical practice as a complementary test to stratify the risk of developing HCC in those patients.

Volume

18

Issue

6

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