Sleep Disturbance and Associated Factors in Hepatocellular Carcinoma Patients Receiving HAIC Combined with Immunotherapy and Targeted Therapy: A Cross-Sectional Study

Purpose: This study assessed the prevalence of sleep disturbance and associated factors in patients with hepatocellular carcinoma (HCC) receiving hepatic arterial infusion chemotherapy (HAIC) combined with targeted therapy and immunotherapy. Patients and Methods: A cross-sectional survey enrolled 230 patients undergoing HAIC combined with targeted therapy and immunotherapy at Sun Yat-sen University Cancer Center (July–November 2025). Sleep, psychological distress, pain, appetite, and quality of life were assessed using the PSQI, HADS, NRS, VAS, and EORTC QLQ-C30, respectively, along with prior HAIC cycles. Logistic regression identified factors associated with sleep disturbance. Results: The prevalence of sleep disturbance (PSQI > 5) was 72.6% (167/230). Univariate analysis identified a greater number of prior HAIC cycles, higher levels of depressive and anxiety symptoms, and lower quality of life and appetite as significant factors. In multivariate analysis, four factors remained independently associated with sleep disturbance: prior HAIC cycles (OR = 1.66, 95% CI: 1.25– 2.20, P < 0.001), anxiety symptoms (OR = 1.27, 95% CI: 1.12– 1.44, P < 0.001), depressive symptoms (OR = 1.23, 95% CI: 1.03– 1.47, P = 0.021), and appetite sensations (OR = 0.93, 95% CI: 0.91– 0.96, P < 0.001), which showed an inverse association with sleep disturbance. The model showed an apparent area under the ROC curve of 0.92 (95% CI 0.87– 0.96), with an optimism-corrected AUC of 0.91 after bootstrap resampling. Conclusion: Sleep disturbance was highly prevalent and was independently associated with cumulative treatment burden, psychological distress and impaired appetite. These cross-sectional findings support routine sleep screening together with psychological and nutritional assessment in this population; whether modifying these factors improves sleep quality requires prospective interventional studies. Keywords: hepatocellular carcinoma, sleep disturbance, hepatic arterial infusion chemotherapy, immunotherapy, targeted therapy