Combined Immunotherapy and Targeted Therapy for Hepatocellular Carcinoma

Inclusion Criteria:

* Pathological diagnosis of primary hepatocellular carcinoma, BCLC stage A, liver function Chid-Pugh grade A, or liver function Child-Pugh classification changed from grade B to grade A after short-term liver treatment, PS score 0- 1 point. Received surgical treatment of primary hepatocellular carcinoma (RO resection).
* Complete resection of postoperative macroscopic and imaging, no residual cancer;
* No large blood vessels (2-pole branches) and bile duct invasion, no macroscopic tumor thrombus;
* Negative margin: the margin of the liver is \>1 cm from the tumor boundary; if the margin is \<1 cm, but the histological examination of the resected liver section showed no residual tumor cells, that is, the margin was negative;
* AFP negative: \<20 ug/L;
* No lymph node invasion, no distant metastasis;
* Laboratory inspection inclusion criteria:

  * Neutrophils ≥ 1.5 × 109 / L;
  * Platelets ≥ 50 × 109 / L;
  * Hemoglobin ≥ 90 g / L;
  * Serum creatinine ≤ 1.5 × upper limit of normal (ULN) and creatinine clearance ≥ 50 mL/min;
  * AST, ALT ≤ 2.5 × ULN;
  * Serum bilirubin ≤ 1.25 × ULN;
  * Patients who did not receive anticoagulant therapy: INR or aPTT ≤ 1.5 × ULN. If the patient received prophylactic anticoagulant therapy, the INR ≤ 2 × ULN within 14 days before the study treatment and the aPTT was within the normal range, the patients were acceptable for enrollment.
* With one of the following high risk factors:

  * Single lesion \>5cm;
  * Single lesion, 3-5cm, with MVI M1/M2;
  * Single lesion, \<3cm, MVI M2;
  * Multiple lesions (2-3)
* General inclusion criteria:

  * Age 18-75;
  * No anti-tumor treatment history before surgery;
  * Agree to provide tissue and pathological specimens;
  * ECOG 0 points;
  * For women of gestational age, no pregnancy plan and continued full contraception.

Exclusion Criteria:

* Pathological diagnosis of primary hepatocellular carcinoma, BCLC stage B, C, D, liver function Child-Pugh grade C, PS score of 2 points and above. Biliary cells or mixed cell carcinoma confirmed by postoperative pathology. No surgery was performed.
* Preoperative treatment of TACE or radiotherapy and chemotherapy, and targeted anti-tumor therapy.
* One month after the operation, the rest of the anti-tumor treatment was performed, or combined with two or more anti-tumor pain treatment.
* There were lymph nodes and distant metastases before surgery.
* Have a history of active autoimmune disease or autoimmune disease;
* Inoculated with any anti-infective vaccine (such as influenza vaccine, varicella vaccine, etc.) within 4 weeks before randomization;
* Use immunosuppressive agents, or systemic, or absorbable local hormones to achieve immunosuppressive purposes (dose \> 10 mg/day of prednisone or other equivalent hormones) and continue to be used within 2 weeks prior to randomization;
* Any significant clinical and laboratory abnormalities;
* Researchers believed that the patient effected safety evaluation, such as: uncontrollable active infections, uncontrolled diabetes, high blood pressure could not be reduced to the following range by monotherapy (systolic blood pressure \< 140 mmHg, diastolic blood pressure \< 90 mmHg), peripheral neuropathy grade II or above, congestive heart failure, myocardial infarction within 6 months, chronic kidney disease;
* Main or main branch tumor thrombus (preoperative imaging or intraoperative findings) or extrahepatic disseminated or recurrent liver cancer.