Infusion of PD1/PDL1/CTLA4 Inhibitors Via Hepatic Arterial for Immunotherapy of Hepatocellular Carcinoma

Inclusion Criteria:

1. Cytohistological confirmation is required for diagnosis of HCC.、
2. Signed informed consent before recruiting
3. Age between 18 to 80 years with estimated survival over 3 months.
4. Child-Pugh class A or B/Child score \> 7; ECOG score \< 2
5. Tolerable coagulation function or reversible coagulation disorders
6. Laboratory examination test within 7 days prior to procedure: WBC≥3.0×10E9/L; Hb≥90g/L； PLT ≥50×10E9/L；INR \< 2.3 or PT \< 6 seconds above control；Cr ≤ 145.5 umul/L；Albumin \> 28 g/L；Total bilirubin \< 51 μmol/L
7. At least one tumor lesion meeting measurable disease criteria as determined by RECIST v1.1.
8. Patients with advanced (unresectable and/or metastatic, stage C based on Barcelona-Clinic Liver Cancer \[BCLC\] staging classification) hepatocellular carcinoma which would not be suitable for treatment with loco-regional therapies or have progressed following locoregional therapy such as surgical resection, percutaneous hepatic arterial embolization, radiofrequency ablation, and percutaneous interventional therapy.
9. Birth control.
10. Willing and able to comply with scheduled visits, treatment plan and laboratory tests.

Exclusion Criteria:

1. Patients participated in clinical trials of equipment or drugs (signed informed consent) within 4 weeks;
2. Patients accompany by ascites, hepatic encephalopathy and esophageal and gastric varices bleeding;
3. Any serious accompanying disease, which is expected to have an unknown, impact on the prognosis, include heart disease, inadequately controlled diabetes and psychiatric disorders;
4. Patients accompanied with other tumors or past medical history of malignancy;
5. Pregnant or lactating patients, all patients participating in this trial must adopt appropriate birth control measures during treatment;
6. Patients have poor compliance.

   Any contraindications for hepatic arterial infusion procedure:

   A.Impaired clotting test (platelet count \< 60000/mm3, prothrombin activity \< 50%).

   B.Renal failure / insufficiency requiring hemo-or peritoneal dialysis. C.Known severe atheromatosis. D.Known uncontrolled blood hypertension (\> 160/100 mm/Hg).
7. Patients have the past history of liver cancer treatment, such as transplantation, resection, radiotherapy, chemotherapy and so on;
8. Allergic to adriamycin chemotherapy drugs，contrast agent and lipiodol;
9. Any agents which could affect the absorption or pharmacokinetics of the study drugs
10. Subjects unable to suffer the discomfort of the HAI procedure