Preoperative systemic immunothrombotic state class is associated with microvascular invasion and early recurrence after curative resection for hepatocellular carcinoma
5 affiliations
- 1School of Medicine, University of Electronic Science and Technology of China
- 2Department of Geriatric Infectious Diseases, Sichuan Academy of Medical Sciences, Sichuan Provincial People’s Hospital, School of Medicine, University of Electronic Science and Technology of China
- 3Department of Oncology, Guizhou Provincial People’s Hospital
- 4Department of Oncology and Cancer Institute, Sichuan Academy of Medical Sciences, Sichuan Provincial People’s Hospital, School of Medicine, University of Electronic Science and Technology of China
- 5Department of Laboratory Medicine and Sichuan Provincial Key Laboratory for Human Disease Gene Study, Sichuan Provincial People’s Hospital, University of Electronic Science and Technology of China
Abstract
Background: Microvascular invasion (MVI) and early recurrence limit durable benefit after curative resection for hepatocellular carcinoma (HCC). We assessed whether an outcome-blinded preoperative systemic immunothrombotic state was associated with pathological MVI and 24-month recurrence and examined NET-associated circulating and tissue markers.
Methods: This observational cohort included 520 patients undergoing curative-intent HCC resection. Three systemic immunothrombotic state classes were derived without outcome information from six preoperative immune-coagulation components; a continuous principal-component burden score was examined supportively. MVI was evaluated using multivariable logistic regression with 30-fold multiple imputation. Twenty-four-month recurrence was analyzed using Fine-Gray competing-risk models, treating death without recurrence as a competing event. Circulating H3Cit and MPO-DNA were measured in 302 patients with valid paired assays. A balanced nested tissue subset of 72 patients selected by state class and MVI status underwent quantitative H3Cit/MPO and CD8 spatial assessment.
Results: High versus low state class was associated with MVI (OR 2.51, 95% CI 1.42–4.43; P = 0.002) and 24-month recurrence (sHR 1.87, 95% CI 1.28–2.74; P = 0.001), whereas the intermediate class was not significantly associated with either outcome. The continuous burden score showed supportive associations with both outcomes. Circulating H3Cit and MPO-DNA increased across state classes, but neither was independently associated with MVI after multivariable adjustment. In the tissue subset, high state class was associated with greater peritumoral and intratumoral H3Cit/MPO-positive density. Circulating H3Cit remained associated with peritumoral H3Cit/MPO density after adjustment for state class, MVI, and age, whereas corresponding MPO-DNA and intratumoral associations were weaker. CD8 spatial exclusion did not differ significantly by state class.
Conclusion: A high preoperative systemic immunothrombotic state was associated with pathological MVI and 24-month recurrence after HCC resection. The clearest blood-tissue concordance involved circulating H3Cit and peritumoral H3Cit/MPO density. The state class added only modest internal discrimination, supporting external validation before clinical application and further mechanistic work to define the role of NET-associated activity.
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BibTeX
@article{geng2026preoperative,
title = {{Preoperative systemic immunothrombotic state class is associated with microvascular invasion and early recurrence after curative resection for hepatocellular carcinoma}},
author = {Xiaoxia Geng and Ting Feng and Xuebei Du and Zi Wang and Lifu Zhu and Chenhui Cao},
journal = {Frontiers in Immunology},
year = {2026},
month = nov,
doi = {10.3389/fimmu.2026.1971472},
url = {https://www.frontiersin.org/articles/10.3389/fimmu.2026.1971472/full},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Preoperative systemic immunothrombotic state class is associated with microvascular invasion and early recurrence after curative resection for hepatocellular carcinoma
AU - Xiaoxia Geng
AU - Ting Feng
AU - Xuebei Du
AU - Zi Wang
AU - Lifu Zhu
AU - Chenhui Cao
PY - 2026
DA - 2026/11/03
JO - Frontiers in Immunology
DO - 10.3389/fimmu.2026.1971472
UR - https://www.frontiersin.org/articles/10.3389/fimmu.2026.1971472/full
AB - Background: Microvascular invasion (MVI) and early recurrence limit durable benefit after curative resection for hepatocellular carcinoma (HCC). We assessed whether an outcome-blinded preoperative systemic immunothrombotic state was associated with pathological MVI and 24-month recurrence and examined NET-associated circulating and tissue markers. Methods: This observational cohort included 520 patients undergoing curative-intent HCC resection. Three systemic immunothrombotic state classes were derived without outcome information from six preoperative immune-coagulation components; a continuous principal-component burden score was examined supportively. MVI was evaluated using multivariable logistic regression with 30-fold multiple imputation. Twenty-four-month recurrence was analyzed using Fine-Gray competing-risk models, treating death without recurrence as a competing event. Circulating H3Cit and MPO-DNA were measured in 302 patients with valid paired assays. A balanced nested tissue subset of 72 patients selected by state class and MVI status underwent quantitative H3Cit/MPO and CD8 spatial assessment. Results: High versus low state class was associated with MVI (OR 2.51, 95% CI 1.42–4.43; P = 0.002) and 24-month recurrence (sHR 1.87, 95% CI 1.28–2.74; P = 0.001), whereas the intermediate class was not significantly associated with either outcome. The continuous burden score showed supportive associations with both outcomes. Circulating H3Cit and MPO-DNA increased across state classes, but neither was independently associated with MVI after multivariable adjustment. In the tissue subset, high state class was associated with greater peritumoral and intratumoral H3Cit/MPO-positive density. Circulating H3Cit remained associated with peritumoral H3Cit/MPO density after adjustment for state class, MVI, and age, whereas corresponding MPO-DNA and intratumoral associations were weaker. CD8 spatial exclusion did not differ significantly by state class. Conclusion: A high preoperative systemic immunothrombotic state was associated with pathological MVI and 24-month recurrence after HCC resection. The clearest blood-tissue concordance involved circulating H3Cit and peritumoral H3Cit/MPO density. The state class added only modest internal discrimination, supporting external validation before clinical application and further mechanistic work to define the role of NET-associated activity.
SN - 1664-3224
ER -