Radiofrequency Ablation Plus Systematic Neoadjuvant Therapy for Recurrent Hepatocellular Carcinoma (RANT Study)

Inclusion Criteria:

* Research subjects understand the research content and significance, and provide the written informed consent;
* age 18 - 75 years and gender is not limited;
* a history of liver resection or RFA for HCC which was clinically or pathologically diagnosed according to the standard of the American Association for the Study of Liver Diseases; the number of lesions ≤ 3, the largest lesion ≤ 3 cm, as demonstrated on by contrast enhanced CT/MRI;
* Patients who are unable or unwilling to undergo liver resection, and have not received other anti-tumor therapies before detection of the recurrence;
* Child Pugh A (≤ 7 points), no pleural ascites and hepatic encephalopathy requiring treatment; Eastern Cooperative Oncology Group (ECOG) Performance Status score of 0-1;
* Within 7 days before enrollment, have sufficient liver and kidney function, suitable laboratory indicators (untreated): hemoglobin (HGB) ≥ 9.0 g/dl, neutrophils ≥ 1,500/mm3, PLT ≥ 50×109/L, serum ALB ≥ 28 g/L, TBIL \< 50 umol/L, ALT, AST \< 5 times the upper limit of normal, Bun, Cr \< 1.5 times the upper limit of normal, INR \< 1.7 or prolonged PT \< 4 s;
* Consent to take the immune checkpoint inhibitor and molecular-targeted drugs;
* No other diseases affecting RFA treatment and targeted therapy combining with immune checkpoint inhibitors.

Exclusion Criteria:

* Patients who have a history of immune checkpoint inhibitor or targeted therapy;
* Tumor invades the branch or trunk of portal vein;
* Patients with extrahepatic metastasis;
* Patients who have an active autoimmune disease or a history of autoimmune disease, hyperthyroidism or hypothyroidism, asthma requiring bronchodilator treatment.
* Patients who have significant cardiovascular disease (heart failure grade Ⅲ or higher as defined by the New York Heart Association), myocardial infarction, unstable arrhythmia, unstable angina pectoris that occurred within 3 months before treatment;
* Patients who have a history of idiopathic pulmonary fibrosis, organizing pneumonia (such as bronchiolitis obliterans), drug-induced pneumonia, idiopathic pneumonia, or an evidence of active pneumonia during chest CT scan screening;
* Patients who have received allogeneic stem cell or solid organ transplantation (including liver transplantation);
* Patients who have taken any anti-tumor Chinese herbal medicine within 7 days before enrollment;
* Patients who have any other diseases, metabolic disorders, abnormal results of physical examination or laboratory tests, which may lead to contraindication to the use of the experimental drugs, or affect the reliability of the research results, or leave the patient at high risk of treatment complications, or affect patient compliance.