A Study of TAE+HAIC Combined With Camrelizumab and Apatinib in the Treatment of Advanced Hepatocellular Carcinoma

Inclusion Criteria:

* 1\. The subjects voluntarily joined the study, had good compliance, cooperated with follow-up, and obtained written informed consent;
* 2\. Age: 18 years old ≤80 years old, both male and female;
* 3\. In accordance with the "Norms for the Diagnosis and Treatment of Primary Liver Cancer (2022 edition)" formulated by the National Health Commission and the 2018 EASL liver Cancer guidelines formulated by the European Association for the Study of Hepatology, a definite diagnosis of hepatocellular carcinoma has been made and pathological results have been obtained;
* 4\. There is at least one measurable lesion (spiral CT scan diameter ≥10mm or malignant lymph node short diameter ≥15mm according to RECIST1.1 standard, see Annex 5 for RECIST version 1.1);
* 5\. Have not received systematic treatment before;
* 6.CNLC was divided into stages Ⅱa-Ⅲb;
* 7\. Meet the status of high tumor load, and meet one of the following conditions: 1) High tumor load is defined according to the 7-11 criteria: combined with the number of tumors and the maximum tumor size, high tumor load is defined as and \> 11; 2) Combined with primary branch of portal vein and main cancer thrombus;
* 8\. The Child-Pugh classification of liver function is grade A or B (5-8 points);
* 9.ECOG PS score 0-1;
* 10\. Expected survival ≥12 weeks;
* 11\. If the patient has active hepatitis B virus (HBV) infection: if HBV-DNA≤2000, treatment can be started directly; If HBV-DNA \> 2000, start antiviral therapy for one week and then start treatment.
* 12\. The major organs function properly and meet the following criteria:

  1. The standard of blood routine examination must meet: (no blood transfusion within 14 days)

     1. Hemoglobin (HB) ≥100g/L,
     2. White blood cell count (WBC)≥3×10\^9/L
     3. Absolute neutrophil count (ANC)≥1.5×10\^9/L,
     4. Platelet (PLT)≥50×10\^9/L;
  2. Biochemical examination shall meet the following standards:

     1. Bilirubin (BIL)\<1.5 times the upper limit of normal (ULN);
     2. Alanine aminotransferase (ALT) and aspartate aminotransferase AST\<5ULN;
     3. Serum creatinine (Cr) ≤1.5ULN
* 13\. Women of childbearing age must have a negative pregnancy test (serum) or urine HCG test within 7 days prior to admission and be willing to use an appropriate method of contraception during the trial period and 8 weeks after the last dose of the test drug; For men, they should be surgically sterilized or consent to an appropriate method of contraception during the trial and for 8 weeks after the last dose of the trial drug.

Exclusion Criteria:

* 1\. Pregnant or lactating women;
* 2\. Patients with autoimmune diseases, organ/hematopoietic stem cell transplantation, or other malignancies (except cured skin basal cell carcinoma and cervical carcinoma in situ);
* 3\. Patients with consciousness disorder or inability to cooperate with treatment, combined with mental illness;
* 4\. Patients who have participated in other clinical trials in the past three months;
* 5\. Received local treatment (such as surgical resection, radiation therapy, ablative therapy, interventional therapy, etc.) within the past 1 month;
* 6\. Thrombotic or embolic events, such as cerebrovascular accidents (including transient ischemic attacks), deep vein thrombosis, or pulmonary embolism, except portal vein thrombosis, occurred within 6 months prior to the first dose of the study drug;
* 7\. Immunosuppressants or systemic hormone therapy (dose \>10mg/ day prednisone or other therapeutic hormones) were used within 14 days before enrollment to achieve immunosuppression;
* 8\. Esophageal (fundus) varices rupture and bleeding within 1 month before treatment;
* 9\. Uncorrectable coagulation dysfunction and severe blood abnormalities, with a tendency to severe bleeding; Platelet count \< 50×109/L and severe coagulation dysfunction can not withstand surgery (anticoagulant therapy and/or anticoagulant drug use should be stopped more than 1 week before radiotherapy);
* 10\. Refractory ascites, bad fluid;
* 11\. Active infection, especially inflammation of the biliary system;
* 12\. Severe liver, kidney, heart, lung, brain and other major organ failure;
* 13\. Previous use of targeted drugs, any component of PD-1 MAB or other similar tests A quick person;
* 14\. Patients with hypertension who cannot be reduced to the normal range by antihypertensive medication (systolic blood pressure \> 140 mmHg, diastolic blood pressure \> 90 mmHg);
* 15\. Previous serious cardiovascular disease, including but not limited to the following diseases: Grade II or above myocardial ischemia or myocardial infarction, poorly controlled arrhythmias (including QTc interval ≥450 ms in men and ≥470 ms in women); According to NYHA criteria, patients with grade Ⅲ to Ⅳ cardiac insufficiency or left ventricular ejection fraction (LVEF) \< 50% indicated by cardiac color ultrasound;
* 16\. Patients with positive urinary protein (urinary protein test 2+ or more, or 24-hour urinary protein quantity \> 1.0g);
* 17\. Inability to swallow tablets, malabsorption syndrome or any condition affecting gastrointestinal absorption;
* 18\. Patients with other concomitant diseases that, in the judgment of the investigator, endanger the patient's safety or interfere with the patient's completion of the study.
* 19\. Patients who do not wish to undergo histological examination to confirm the diagnosis.