Objective To evaluate the efficacy of postoperative adjuvant targeted-immuno-therapy of hepatocellular carcinoma (HCC) patients with high‑risk recurrence factors.

Methods The propensity score matching (PSM) and retrospective cohort study was conducted. The clinicopatholo-gical data of 431 HCC patients with high‑risk recurrence factors who were admitted to The First Affiliated Hospital of University of Science and Technology of China between January 2020 and December 2023 were collected.There were 359 males and 72 females, aged (59±10)years. Patients underwent radical hepatectomy. Of 431 patients, 60 cases receiving postoperative adjuvant targeted-immunotherapy were allocated into adjuvant therapy group, and 371 patients not receiving post-operative adjuvant targeted‑immunotherapy were allocated into surveillance group. Observation indicators: (1)PSM and comparison of general data of patients between the two groups after matching; (2) prognostic analysis of patients; (3) analysis of factors influencing recurrence‑free survival (RFS) of patients; (4) subgroup analysis; (5) safety analysis. Comparison of measurement data with normal distribution between groups was conducted using the independent sample t test. Comparison of measurement data with skewed distribution between groups was conducted using the Mann‑Whitney U test. Comparison of count data between groups was conducted using the chi-square test or Fisher exact probability. Comparison of ordinal data was conducted using the non-parameter rank sum test. The Kaplan‑Meier method was used to calculate survival rates and plot survival curves, and Log‑rank test was used for survival analysis.The multivariate Cox regression model was used for univariate and multivariate analyses. Subgroup survival analysis was conducted using univariate Cox regression model, and forest plots were generated. PSM was performed using the 1∶2 optimal full matching method with a caliper value of 0.02.

Results (1)PSM and comparison of general data of patients between the two groups after matching. Of the 431 patients, 180 cases were successfully matched, with 60 cases in the adjuvant therapy group and 120 cases in the surveillance group. After PSM, the elimination of alanine aminotransferase level and postoperative adjuvant transcatheter arterial chemoembolization confounding bias ensured comparability. (2) Prognostic analysis of patients. After PSM, the median RFS time was 31.8 months and 1‑, 2‑, 3‑year RFS rates were 81.7%, 55.3%, 46.8% in the adjuvant therapy group, versus 17.2 months and 56.7%, 44.2%, 34.7% in the surveillance group, showing a significant difference in RFS between the two groups (χ²=4.984, P<0.05). (3) Analysis of factors influencing RFS of patients. Results of multivariate analysis showed that microvascular invasion, portal vein invasion, and satellite nodules were inde-pendent risk factors for postoperative RFS of HCC patients with high‑risk recurrence factors (hazard ratio=1.955, 2.524, 1.883, 95% confidence interval as 1.141-3.347, 1.346-4.734, 1.262-2.812, P<0.05). Postoperative adjuvant targeted‑immunotherapy was an independent protective factor for postoperative RFS of HCC patients with high‑risk recurrence factors(hazard ratio=0.580, 95% confidence interval as 0.378-0.889, P<0.05). (4) Subgroup analysis. After PSM, postoperative adjuvant targeted-immunotherapy improved RFS in subgroups including patients as female, aged ≤65 years, or with albumin‑bilirubin grade 2, platelet count ≥100×10⁹/L, hepatitis, cirrhosis, tumor margin distance <1 cm, Edmondson-Steiner grade Ⅲ-Ⅳ, solitary tumor, presence of microvascular invasion, absence of portal vein invasion, and presence of satellite nodules (P<0.05). (5) Safety analysis. The median number of treatment cycles in the adjuvant therapy group was 11(5,16). Sixteen patients discon-tinued treatment permanently due to non‑recurrence events. During treatment, 58 patients in the adjuvant therapy group experienced adverse events, including 42 cases of grade 1 or 2 adverse events, and 16 cases of grade 3 adverse events. No treatment‑related death occurred.

Conclusion Postoperative adjuvant targeted‑immunotherapy can improve RFS in HCC patients with high‑risk recurrence factors and demonstrate a favorable safety and tolerability profile with manageable adverse events.