Distinct immune signatures define hepatitis D– versus hepatitis B–associated hepatocellular carcinoma
Simon Glimmann, Katja Deterding, Kilian Bock, Birgit Bremer, Anke R.M. Kraft, Markus Cornberg, Heiner Wedemeyer, Bernd Heinrich, Anika WrankeBackground:
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
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.