Inclusion Criteria:
1. The patient voluntarily joined the study and signed an informed consent form;
2. ≥18 and ≤ 75 years old, both male and female;
3. Clinically diagnosed or pathologically confirmed hepatocellular carcinoma, at least one measurable focus without local treatment (according to mRECIST requirements, the measurable focus spiral CT scan length ≥ 10 mm or enlargement Short diameter of lymph node ≥15 mm);
4. Child-Pugh score ≤ 13 points;
5. BCLC-C stage accompanied by tumor thrombosis-associated portal hypertension;
6. Newly diagnosed patients who have not received targeted therapy or immunotherapy in the past;
7. ECOG score: 0～1;
8. Expected survival period ≥ 12 weeks;
9. The functions of vital organs meet the following requirements (no blood components, cell growth factors and other corrective treatment drugs are allowed within 14 days before the first administration):
10. The absolute count of neutrophils≥1.5×109/L; Platelet ≥50×109/L; Hemoglobin ≥60 g/L; Serum albumin ≥28 g/L; Thyroid-stimulating hormone (TSH)≤1×ULN (if abnormal, the levels of FT3 and FT4 should be examined at the same time, if the levels of FT3 and FT4 are normal, they can be included in the group); Bilirubin≤2×ULN (within 7 days before the first administration); ALT and AST ≤5×ULN (within 7 days before the first dose); Serum creatinine≤1.5×ULN;
11. Non-surgical sterilization or female patients of childbearing age need to use a medically approved contraceptive method (such as an intrauterine device, contraceptive, or condom) during the study treatment period and within 3 months after the end of the study treatment period; Female patients of childbearing age who undergo surgical sterilization must be negative in serum or urine HCG within 72 hours before enrollment in the study; and must be non-lactating; for male patients whose partners are women of childbearing age, at the last time use effective methods for contraception within 3 months.
Exclusion Criteria:
1. The patient has any active autoimmune disease or a history of autoimmune disease;
2. The patient is using immunosuppressive agents or systemic hormone therapy to achieve the purpose of immunosuppression (dose\>10mg/day prednisone or other curative hormones), and continues to use it within 2 weeks before enrollment;
3. The number of system treatment lines ≥ 2 lines;
4. Severe allergic reaction to other monoclonal antibodies;
5. Those with a known history of central nervous system metastasis or hepatic encephalopathy;
6. Patients who have received liver transplantation in the past;
7. Tumor thrombus beyond the portal vein range, such as hepatic vein, inferior vena cava, right atrium, splenic vein, superior mesenteric vein cancer thrombus, etc.;
8. Suffer from high blood pressure and cannot be well controlled by antihypertensive drugs (systolic blood pressure ≥140 mmHg or diastolic blood pressure ≥90 mmHg);
9. Uncontrolled cardiac clinical symptoms or diseases, such as: NYHA level 2 or higher heart failure, unstable angina pectoris, myocardial infarction occurred within 1 year, clinically significant supraventricular or ventricular arrhythmia requires treatment or intervention , QTc\>450ms (male); QTc\>470ms (female);
10. Abnormal coagulation function (INR\>2.0, PT\>16s), have bleeding tendency or are receiving thrombolysis or anticoagulation therapy, and allow the preventive use of low-dose aspirin and low molecular heparin;
11. Child-Pugh score \>13 points;
12. Arterial/venous thrombosis events that occurred within 6 months before randomization, such as cerebrovascular accidents (including temporary ischemic attacks, cerebral hemorrhage, cerebral infarction), deep vein thrombosis, and pulmonary embolism;
13. Known genetic or acquired bleeding and thrombotic tendency (such as hemophilia patients, coagulation dysfunction, thrombocytopenia, etc.); Urine routine test showed urine protein ≥ ++ and confirmed 24-hour urine protein content\> 1.0 g;
14. Patients who have previously received radiotherapy, chemotherapy, hormone therapy, and surgery, after the completion of the treatment (last medication) and less than 4 weeks before the study medication; molecular targeted therapy (including other oral targeted drugs used in clinical trials) is less than the first study medication \<5 drug half-lives, or patients whose adverse events (except alopecia) caused by previous treatment have not recovered to ≤ CTCAE level 1;
15. The patient has active infection, fever of unknown origin within 7 days before medication ≥38.5℃, or baseline white blood cell count \>15×109/L; Patients with congenital or acquired immune deficiencies (such as HIV-infected persons);
16. Moderate to severe pulmonary hypertension, pulmonary artery pressure was assessed by ultrasound \>40mmHg；
17. The patient suffered from other malignant tumors in the past 3 years or at the same time (except for cured skin basal cell carcinoma and cervical carcinoma in situ);
18. Central nervous system metastasis；
19. The patient has previously received other anti-PD-1 antibody therapy or other immunotherapy against PD-1/PD-L1, or has previously received apatinib therapy;
20. Live vaccine may be vaccinated less than 4 weeks before study medication or may be administered during the study period;
21. According to the judgment of the investigator, the patient has other factors that may affect the results of the study or cause the study to be terminated halfway, such as alcoholism, drug abuse, other serious diseases (including mental illness) that require combined treatment, and serious laboratory tests 22. Abnormalities, accompanied by family or social factors, will affect the safety of patients.
