This study investigates the clinical efficacy and safety of transarterial chemoembolization (TACE) combined with the immune agent nivolumab compared to TACE alone for treating hepatocellular carcinoma (HCC). The study aims to determine if the combination therapy can more effectively inhibit tumor angiogenesis, improve clinical benefit rates, and prolong survival, while maintaining a high safety profile.

Hepatocellular carcinoma (HCC) is a common malignancy with high mortality. While TACE is a standard treatment, it can paradoxically stimulate tumor angiogenesis. Immune checkpoint inhibitors have shown promise in HCC, but single-agent efficacy is limited. This study was designed to evaluate whether combining TACE with hepatic arterial infusion of an immune agent (nivolumab) could improve outcomes by inhibiting tumor angiogenesis and enhancing anti-tumor immune responses. Patients diagnosed with unresectable HCC (BCLC stages A, B, C; Child-Pugh A or B) were randomized to receive either TACE alone (control group) or TACE combined with hepatic arterial infusion of nivolumab (study group). The study assessed objective response rate (ORR), disease control rate (DCR), changes in angiogenesis factors (VEGF, VEGFR-2, Ang-2) and tumor markers (CEA, AFP, CA199) before and one month after treatment. Adverse reactions, overall survival (OS), and progression-free survival (PFS) were also evaluated.

Inclusion Criteria:

• Age >18 years;
• Diagnosis of HCC according to the Diagnosis and Treatment Guidelines for Primary Liver Cancer (2024 Edition), confirmed by pathological examination;
• Barcelona Clinic Liver Cancer (BCLC) stages A, B, and C, with non-resectable tumors;
• Liver function graded as Child-Pugh A or B;
• At least one measurable lesion according to the Response Evaluation Criteria in Solid Tumors (RECIST) 1.1;
• Eastern Cooperative Oncology Group (ECOG) performance status score of 0-2;
• No severe hematologic abnormalities or immune deficiencies;
• Expected survival time >6 months.

Exclusion Criteria:

• Recurrent liver cancer or metastatic cancer from other organs;
• Previous treatment with other antitumor therapies, including surgery, radiotherapy, chemotherapy, targeted therapy, or immunotherapy;
• History of other malignant tumors;
• Pregnant or lactating women;
• Human immunodeficiency virus (HIV) infection;
• Severe cardiovascular, pulmonary, cerebral, or renal diseases;
• Active bleeding or coagulopathy outside the liver;
• Enrollment in another clinical trial or participation in a clinical trial within one month prior to admission;
• Psychiatric disorders or unstable mental status;
• Allergic reactions to the study drugs;
• Severe gastrointestinal diseases, such as active ulcers, or other conditions affecting drug absorption.