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Page 2 of 12 Yu et al. Hepatoma Res. 2025;11:29 | https://dx.doi.org/10.20517/2394-5079.2025.47

TACE plus immunotherapy in HCC patients was constructed. The area under the ROC curve (AUC) for the
prediction model was 0.885 (95% confidence interval: 0.820-0.951), with a cut-off value of 137.786. The model
demonstrated a sensitivity of 0.812 and a specificity of 0.889.

Conclusion: The nomogram model developed in this study shows promising predictive performance for sirAEs in
HCC patients receiving TACE plus immunotherapy; however, further validation in larger, multi-center prospective
cohorts is needed to confirm its generalizability and clinical utility.

Keywords: Hepatocellular carcinoma, transcatheter arterial chemoembolization immunotherapy, immune-related
adverse events, logistic regression analysis, prediction model

INTRODUCTION
Hepatocellular carcinoma (HCC) represents approximately 75%-85% of primary liver cancer cases and is
the sixth most common malignancy globally . Immune checkpoint inhibitors (ICIs) have become
[1]
important treatments for advanced HCC. The Barcelona Clinic Liver Cancer (BCLC, 2022) guideline
recommends first-line immune-targeted therapy with atezolizumab plus bevacizumab or dual
immunotherapy with durvalumab plus tremelimumab for patients with stage B (diffuse, invasive, bilobar
extensive metastases) and C HCC. Guidelines also recommend ramucirumab in HCC patients with alpha-
fetoprotein (AFP) ≥ 400 mg/mL after failure of first-line therapy . In the NCCN (National Comprehensive
[2]
Cancer Network) guideline, atezolizumab plus bevacizumab, durvalumab or pembrolizumab are
recommended as first-line treatments for patients with Child-Pugh Class A .
[3]

Locoregional therapy combined with systemic treatment has become an established strategy in advanced
HCC and has delivered substantial clinical benefit . Among these approaches, transarterial
[4]
chemoembolization (TACE) stands out as the cornerstone of locoregional therapy for intermediate-stage
HCC and is strongly endorsed by multiple international guidelines . For advanced HCC, the Chinese and
[2,3]
Japanese guidelines also recommend the individualized use of TACE as a locoregional palliative therapy .
[5,6]

ICIs enhance the cytotoxicity of immune cells, thereby promoting the elimination of cancer cells. However,
they may also excessively enhance the normal immune response of patients, which may lead to disorders of
the immune system, and then lead to the occurrence of immune-related adverse events (irAEs) . Beyond
[7]
this, TACE reshapes the immune microenvironment of HCC, thereby modulating both the efficacy of
subsequent immunotherapy and the incidence of associated irAEs. The mortality rate of severe irAEs
(sirAEs) (≥ 3 grade) has reached 2% . sirAEs seriously increase the economic and physical burden of
[8]
patients. Therefore, it is of great clinical significance to predict these patients who are prone to developing
sirAEs before therapy. In this study, a nomogram prediction model was constructed based on pre-
therapeutic lymphocyte subpopulation data and clinical characteristics of HCC patients to predict the
occurrence of sirAEs following TACE combined with immunotherapy.

METHODS

Study design and patients
Data regarding lymphocyte subpopulations and clinical characteristics of 156 HCC patients treated from
January 2020 to June 2024 were retrospectively analyzed. After applying predefined inclusion and exclusion
criteria, 46 HCC patients who developed sirAEs were assigned to the sirAEs group, while 84 HCC patients
without sirAEs served as the control group. Blood was obtained from the patient's fasting venous blood