Distinct immune signatures define hepatitis D- versus hepatitis B-associated hepatocellular carcinoma.
5 affiliations
- 1Department of Gastroenterology, Hepatology, Infectious Diseases and Endocrinology, Hannover Medical School, Hannover, Germany.
- 2German Centre for Infection Research (DZIF), Partner Site Hannover-Braunschweig, Hannover, Germany.
- 3Centre for Individualised Infection Medicine (CiiM), a joint venture between the Helmholtz Centre for Infection Research (HZI) and Hannover Medical School (MHH), Hannover, Germany.
- 4Cluster of Excellence RESIST (EXC 2155), Hannover Medical School, Hannover, Germany.
- 5D-SOLVE, EU-funded Network on individualized management of hepatitis D, Hannover, Germany.
Abstract
Background
Hepatocellular carcinoma (HCC) is a leading cause of cancer-related mortality worldwide. Hepatitis D is the most severe form of viral hepatitis. However, the clinical, virological, and systemic inflammatory characteristics of HDV-associated HCC remain insufficiently characterized.Methods
In this single-center retrospective study, we identified 162 patients with HCC due to chronic hepatitis D (HDV-HCC; n=54) or chronic hepatitis B (HBV-HCC; n=108). Plasma levels of 92 soluble inflammatory mediators (SIMs) were quantified using proximity extension assay in HCC patients [HBV-HCC (n=50), HDV-HCC (n=30), and matched non-HCC controls (HBV=19, HDV=17)].Results
At the time of HCC diagnosis, patients with CHD were younger, had more impaired liver synthesis and detoxification function, and lower levels of AST, CRP, and leukocytes. HDV-HCCs presented with smaller tumors, less frequent portal vein infiltration, and more often fulfilled Milan criteria (all p<0.01). Systemic immune profiling revealed distinct inflammatory patterns between both etiologies. Compared with HBV-HCC, HDV-HCC was characterized by a comparatively stronger IL-10-associated immunoregulatory signature, whereas HBV-HCC exhibited a more pronounced pro-inflammatory profile involving IL-6- and phosphorylation- and proliferation-associated signaling. Despite these differences, event-free survival did not differ between groups.Conclusions
HBV-HCC more frequently presented with advanced tumor stage, whereas HDV-HCC was associated with more severe underlying liver disease but smaller tumors. Importantly, HBV-associated and HDV-associated HCC exhibit distinct systemic inflammatory signatures, potentially reflecting differences in systemic immune regulation between etiologies. These findings may have implications for biomarker development and future etiology-specific therapeutic strategies.
Related
- Identification of hepatitis B virus-associated membrane proteins as prognostic biomarkers for hepatocellular carcinoma based on retrospective analysis of integrated membrane proteomics
- Synchronous hepatocellular carcinoma and IPNB-associated intrahepatic cholangiocarcinoma in a patient with resolved viral hepatitis: a case report of diagnostic pitfall and margin-negative resection
- A hybrid deep learning and ensemble approach for accurate prediction of hepatocellular carcinoma from sequence variants of hepatitis B virus (HBV) X gene
- Superior Efficacy of Besifovir in Reducing Hepatocellular Carcinoma Risk Compared to Tenofovir in Chronic Hepatitis B Patients: A Nationwide Cohort Study
- Hepatology: Emerging Paradigms in MASLD, Viral Hepatitis, Cholestatic Liver Disease, Portal Hypertension and Hepatocellular Carcinoma
BibTeX
@article{glimmann2026distinct,
title = {{Distinct immune signatures define hepatitis D- versus hepatitis B-associated hepatocellular carcinoma.}},
author = {Simon Glimmann and Katja Deterding and Kilian Bock and Birgit Bremer and Anke R M Kraft and Markus Cornberg and Heiner Wedemeyer and Bernd Heinrich and Anika Wranke},
journal = {Hepatology communications},
year = {2026},
month = oct,
doi = {10.1097/hc9.0000000000001060},
url = {https://europepmc.org/article/MED/42900159},
note = {CC BY},
}
RIS
TY - JOUR
TI - Distinct immune signatures define hepatitis D- versus hepatitis B-associated hepatocellular carcinoma.
AU - Simon Glimmann
AU - Katja Deterding
AU - Kilian Bock
AU - Birgit Bremer
AU - Anke R M Kraft
AU - Markus Cornberg
AU - Heiner Wedemeyer
AU - Bernd Heinrich
AU - Anika Wranke
PY - 2026
DA - 2026/10/19
JO - Hepatology communications
DO - 10.1097/hc9.0000000000001060
UR - https://europepmc.org/article/MED/42900159
AB - Background Hepatocellular carcinoma (HCC) is a leading cause of cancer-related mortality worldwide. Hepatitis D is the most severe form of viral hepatitis. However, the clinical, virological, and systemic inflammatory characteristics of HDV-associated HCC remain insufficiently characterized.Methods In this single-center retrospective study, we identified 162 patients with HCC due to chronic hepatitis D (HDV-HCC; n=54) or chronic hepatitis B (HBV-HCC; n=108). Plasma levels of 92 soluble inflammatory mediators (SIMs) were quantified using proximity extension assay in HCC patients [HBV-HCC (n=50), HDV-HCC (n=30), and matched non-HCC controls (HBV=19, HDV=17)].Results At the time of HCC diagnosis, patients with CHD were younger, had more impaired liver synthesis and detoxification function, and lower levels of AST, CRP, and leukocytes. HDV-HCCs presented with smaller tumors, less frequent portal vein infiltration, and more often fulfilled Milan criteria (all p<0.01). Systemic immune profiling revealed distinct inflammatory patterns between both etiologies. Compared with HBV-HCC, HDV-HCC was characterized by a comparatively stronger IL-10-associated immunoregulatory signature, whereas HBV-HCC exhibited a more pronounced pro-inflammatory profile involving IL-6- and phosphorylation- and proliferation-associated signaling. Despite these differences, event-free survival did not differ between groups.Conclusions HBV-HCC more frequently presented with advanced tumor stage, whereas HDV-HCC was associated with more severe underlying liver disease but smaller tumors. Importantly, HBV-associated and HDV-associated HCC exhibit distinct systemic inflammatory signatures, potentially reflecting differences in systemic immune regulation between etiologies. These findings may have implications for biomarker development and future etiology-specific therapeutic strategies.
SN - 2471-254X
ER -