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

Year: 2026

Type: article

Abstract: BACKGROUND & AIM: The entry of Hepatitis D Virus (HDV) depends on HBV surface proteins (HBsAg) composed of three isoforms: large-, middle, and small HBsAg. Here, we investigate the levels of total HBsAg and HBsAg isoforms and their correlations with HDV-RNA, HBcrAg, and transaminases in the setting of untreated chronic hepatitis D (CHD). METHODS: This study includes 316 HBeAg-negative patients: 192 CHD and 124 with chronic hepatitis B (CHB) as a control group. HBsAg isoforms were quantified by ad hoc-designed ELISAs. RESULTS: < 0.0001) but not with HBV-DNA. The results were confirmed by stratifying patients according to HDV-RNA (< or >1000 IU/mL) and HBcrAg (< or >3 logU/mL). Furthermore, CHD patients with ALT > upper limit of normal presented significantly higher S-HBsAg and M-HBsAg levels. CONCLUSIONS: CHD is characterized by a more elevated HBsAg isoform production, paralleling HDV-RNA and HBcrAg release. This may suggest a preferential recruitment of HBsAg isoforms in HDV virions at the expense of HBV virions. The association of HBsAg isoforms with higher ALT also suggests their potential contribution in supporting HDV-induced pro-inflammatory stimuli.

Source: Viruses

DOI: 10.3390/v18050515

Institutions: University of Rome Tor Vergata, University of Turin, Policlinico Tor Vergata, University of Bari Aldo Moro, Link Campus University, University of Milan, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico

Language: English

Topic: Hepatitis B Virus Studies

Subfield: Epidemiology

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $3,137

Funders: European Federation of Pharmaceutical Industries and Associations, Innovative Health Initiative, European Commission, HORIZON EUROPE Framework Programme

Award: G7087703579

OpenAlex ID: W7160143324