HLA-A*11:01 Identifies Patients at Risk for Persistent Viraemia and Advanced Fibrosis in HDV Infection.

Authors

Maria Francesca Cortese, Adriana Palom, Ariadna Rando Segura, Francesc Rudilla, Emma Enrich Rande, Arnau Puig Lopez, David Tabernero Caellas, Judit Vico Romero, Juan Carlos Ruiz-Cobo, Mar Riveiro-Barciela, Maria José Herrero, Maria Buti

Published in

Alimentary pharmacology & therapeutics. Sep 10, 2026. Epub Sep 10, 2026.

Abstract

Hepatitis delta virus (HDV) infection causes the most severe form of viral hepatitis, with highly heterogeneous outcomes ranging from viral control to persistent viraemia and progressive liver disease. The Human Leukocyte Antigen (HLA) system plays a central role in antiviral immunity, yet its contribution to HDV disease remains poorly defined. We aimed to identify HLA genetic polymorphisms associated with virological control and disease severity.
High-resolution genotyping of classical (A, B, C, DPB1, DQB1, DRB1) and non-classical (E, G) HLA was performed in 72 anti-HDV-positive patients. A group of healthy donors (N = 150) was used as a reference. Patients were stratified by longitudinal HDV RNA status into viraemic (persistent viraemia, N = 36) and non-viraemic (undetectable viraemia, N = 36) groups. Clinical data, including liver fibrosis stage, were collected. T cell receptor (TCR) β-chain sequencing was performed in isolated CD3⁺ T cells from viraemic patients and compared to a group of healthy donors (HD; N = 44).
The HLA-A*11:01 allele was exclusively observed in viraemic patients (p-value < 0.001, FDR = 0.02; allele frequency = 0.15). Multivariate analysis confirmed its independent association with persistent viraemia and advanced fibrosis. Notably, its frequency did not differ between our cohort and the overall reference population. Furthermore, viraemic HLA-A*11:01 carriers exhibited significantly higher TCRβ chain clonality, consistent with a restricted and potentially ineffective antiviral T-cell response.
HLA-A*11:01 identifies a subgroup of HDV patients at high risk of persistent viral replication and advanced fibrosis. The integration of HLA genotyping into risk stratification algorithms may help to early identify patients requiring intensified monitoring and timely therapeutic intervention.

PMID:
42723136
Bibliographic data and abstract were imported from PubMed on 11 Sep 2026.

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