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Chronic HDV Infection Shows Higher HBsAg Isoform Levels than HBV Infection, Paralleling HDV Replicative Activity

Stefano D'Anna1, Lorenzo Piermatteo1, Alessia Magnapera1

  • 1Department of Biology, University of Rome Tor Vergata, 00133 Rome, Italy.

Viruses
|May 27, 2026
PubMed

Insights

Chronic hepatitis D (CHD) shows increased Hepatitis B Surface Antigen (HBsAg) isoforms, correlating with Hepatitis D Virus RNA (HDV-RNA) and Hepatitis B Core Related Antigen (HBcrAg). This suggests HBsAg isoforms may be involved in HDV virion assembly and inflammation.

Area of Science:

  • Hepatology
  • Virology
  • Immunology

Background:

  • Hepatitis D Virus (HDV) entry relies on Hepatitis B Virus (HBV) surface proteins (HBsAg), which exist in large, middle, and small isoforms.
  • Understanding HBsAg isoform dynamics is crucial in chronic hepatitis D (CHD).

Purpose of the Study:

  • To investigate HBsAg isoform levels and their correlation with HDV-RNA, HBcrAg, and transaminases in untreated CHD patients.
  • To compare HBsAg isoform composition between CHD and chronic hepatitis B (CHB) patients.

Main Methods:

  • A cohort of 316 HBeAg-negative patients (192 CHD, 124 CHB) was studied.
  • HBsAg isoforms were quantified using specifically designed ELISAs.
  • Multivariable analysis and stratification by HDV-RNA and HBcrAg levels were employed.

Main Results:

  • CHD patients exhibited significantly higher levels of all HBsAg isoforms compared to CHB patients.
  • HBsAg isoforms positively correlated with HDV-RNA and HBcrAg levels in CHD patients.
  • Elevated alanine transaminase (ALT) levels in CHD patients were associated with higher small and middle HBsAg levels.

Conclusions:

  • Chronic hepatitis D is characterized by increased HBsAg isoform production, mirroring HDV-RNA and HBcrAg levels.
  • This suggests preferential incorporation of HBsAg isoforms into HDV virions.
  • HBsAg isoforms may contribute to HDV-induced inflammation.
Abstract

Keywords:
HBcrAgHBsAg isoformsHDV-RNAchronic hepatitis Dtotal HBsAg

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