Long-term kinetic of HBsAg proteins in patients with HBeAg-negative infection or hepatitis over up to 9 years

M Pfefferkorn; F-L Rößiger; J Seltmann; M Matz-Soja; P Colombatto; A Pinna; T Berg; D Glebe; E Degasperi; M Brunetto; P Lampertico; F van Bömmel

doi:10.1055/s-0045-1810831

Zeitschrift für Gastroenterologie, Inhaltsverzeichnis

Z Gastroenterol 2025; 63(08): e481-e482
DOI: 10.1055/s-0045-1810831

Abstracts | DGVS/DGAV

Kurzvorträge

Virushepatitis im Blick: Zwischen Kontrolle und Herausforderung Donnerstag, 18. September 2025, 11:00 – 12:17, Vortragsraum 10

Long-term kinetic of HBsAg proteins in patients with HBeAg-negative infection or hepatitis over up to 9 years

M Pfefferkorn

¹Division of Hepatology, Department of Medicine II, Leipzig University Medical Center, Leipzig, Deutschland

,

F-L Rößiger

¹Division of Hepatology, Department of Medicine II, Leipzig University Medical Center, Leipzig, Deutschland

,

J Seltmann

¹Division of Hepatology, Department of Medicine II, Leipzig University Medical Center, Leipzig, Deutschland

,

M Matz-Soja

¹Division of Hepatology, Department of Medicine II, Leipzig University Medical Center, Leipzig, Deutschland

²Rudolf-Schönheimer-Institute for Biochemistry, Leipzig University, Leipzig, Deutschland

,

P Colombatto

³University of Pisa, Dept of Clinical and Experimental Medicine, Pisa, Italien

⁴Pisa University Hospital, Hepatology Unit and Laboratory of Molecular Genetics and Pathology of Hepatitis Viruses, Pisaits, Italien

,

A Pinna

³University of Pisa, Dept of Clinical and Experimental Medicine, Pisa, Italien

⁴Pisa University Hospital, Hepatology Unit and Laboratory of Molecular Genetics and Pathology of Hepatitis Viruses, Pisaits, Italien

,

T Berg

¹Division of Hepatology, Department of Medicine II, Leipzig University Medical Center, Leipzig, Deutschland

,

D Glebe

⁵Institute for Medical Virology, National Reference Centre for Hepatitis B viruses and Hepatitis D viruses, Justus Liebig University Giessen, Giessen, Deutschland

,

E Degasperi

⁶CRC "A. M. and A. Migliavacca" Center for Liver Disease, Division of Gastroenterology and Hepatology, Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico, Università degli Studi di Milano, Milan, Italien

,

M Brunetto

³University of Pisa, Dept of Clinical and Experimental Medicine, Pisa, Italien

⁴Pisa University Hospital, Hepatology Unit and Laboratory of Molecular Genetics and Pathology of Hepatitis Viruses, Pisaits, Italien

,

P Lampertico

⁶CRC "A. M. and A. Migliavacca" Center for Liver Disease, Division of Gastroenterology and Hepatology, Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico, Università degli Studi di Milano, Milan, Italien

,

F van Bömmel

¹Division of Hepatology, Department of Medicine II, Leipzig University Medical Center, Leipzig, Deutschland

› Institutsangaben

Abstract

Volltext

Background: Intrahepatic viral activity in patients with HBeAg-negative HBV infection (ENI) or chronic hepatitis B (CHB) has recently been linked to silened cccDNA activity after prolonged infection. While intrahepatic studies are of upmost importance, surrogate markers are in high demand. Lower ratios of large (LHBs) and middle (MHBs) HBsAg proteins have been associated with inactive HBV infection or treatment response.

Aim: We investigated the dynamics of HBsAg proteins during long-term treatment with Tenofovir Disoproxil Fumarate (TDF) or during spontaneous HBsAg loss in patients with chronic HBV infection.

Methods: Serum samples from two patient cohorts with either HBeAg-negative ENI (n=38) or CHB (n=96) were analyzed. The CHB cohort included patients prospectively enrolled during first-line (n=24, group A) or second-line (n=72, group B) TDF treatment. The untreated ENI cohort was retrospectively analyzed, including patients who either lost HBsAg spontaneously (n=19) or remained positive (n=19). HBsAg protein levels and viral markers were quantified at baseline and repeatedly every 1-3 years over up to 9 years.

Results: In CHB patients, median HBsAg (log ng/mL) slightly declined over time from 3.8 (group A) and 3.3 (group B) at baseline to 3.4 and 2.8 after 8 years, respectively (p=n.s.). Importantly, LHBs (%) decreased markedly from baseline values of 9.3% and 9.5% to 4.2% and 4.3% at 3 years, without further decline thereafter. MHBs (%) strongly declined from baseline (13.3% and 10.9%) to 3.7% and 3.0% at 8 years of TDF therapy.

Untreated ENI patients had significantly lower baseline HBsAg levels (log ng/mL: 3.0 with and 2.9 without HBsAg loss), LHBs (3.1% and 4.1%), and MHBs (1.2% and 1.3%) compared to CHB patients (p<0.001). During follow-up, total HBsAg, LHBs, and MHBs levels consistently declined in patients achieving HBsAg loss. Notably, MHBs dropped from 1.2% at baseline to 0.5% after 4-6 years, becoming undetectable early. Conversely, patients without HBsAg loss showed stable or slightly increased MHBs (1.3% to 3.3%) during follow-up.

Conclusion: Long-term TDF treatment in CHB patients led to significant declines in LHBs and MHBs percentages, reflecting reduced viral replication activity. Untreated ENI patients exhibited markedly lower baseline LHBs and MHBs levels, with spontaneous HBsAg loss accompanied by a pronounced decline of HBsAg proteins, particularly early disappearance of MHBs.