Background: Outcomes of transarterial chemoembolization (TACE) combined with programmed cell death-1 (PD-1) inhibitors for unresectable hepatocellular carcinoma (HCC) remain heterogeneous. This study evaluated the prognostic value of the dynamic Systemic Immune-Inflammation Index (Delta SII) and Albumin-Bilirubin (ALBI) grade to construct a predictive nomogram.

Methods: We retrospectively analyzed 168 patients with unresectable HCC treated with TACE plus PD-1 inhibitors. Delta SII was defined as the relative change from baseline to the first follow-up. Independent prognostic factors for Overall Survival (OS) were identified via Cox regression to build a nomogram. Delta SII was categorized into High and Low groups using an optimal cut-off of 32.7%, determined by maximally selected rank statistics. Post-treatment SII (SII_T1) was measured within a prespecified window of 28–42 days post-treatment. The nomogram was internally validated using 500-bootstrap resampling, and performance was assessed by time-dependent Area Under the Curve (AUC) with 95% confidence intervals, calibration plots, and Decision Curve Analysis (DCA). All patients received toripalimab (240 mg every 3 weeks) as the PD-1 inhibitor.

Results: Patients with a High Delta-SII or ALBI Grade 2/3 exhibited significantly inferior OS and Progression-Free Survival (PFS) (p < 0.001). Multivariate analysis identified Tumor Size (Hazard Ratio (HR): 1.10, 95% CI: 1.04–1.16), Tumor Number (HR: 1.34, 95% CI: 1.10–1.63), macrovascular invasion (MVI) (HR: 1.64, 95% CI: 1.08–2.48), ALBI Grade 2/3 (HR: 2.76, 95% CI: 1.62–4.70), and High Delta-SII group (HR: 2.84, 95% CI: 1.86–4.33) as independent risk factors for mortality. The constructed nomogram demonstrated robust discrimination, with AUCs of 0.804 (95% CI: 0.737–0.872) for 1-year and 0.823 (95% CI: 0.756–0.890) for 2-year OS. Calibration curves showed excellent agreement between predicted and observed survival, and DCA confirmed the model's clinical utility.

Conclusion: The dynamic evolution of systemic inflammation (Delta SII) and baseline hepatic reserve (ALBI grade) are powerful synergistic predictors of survival in unresectable HCC patients receiving TACE plus PD-1 inhibitors. The proposed nomogram, which prioritizes host biological resilience over tumor burden alone, offers a precise and visual tool to guide clinical decision-making and identify patients most likely to benefit from this combination therapy.