TIPS Plus Half-dose Donafenib in AHCC with PVTT-associated Portal Hypertension

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. Pathologically confirmed hepatocellular carcinoma, at least one measurable focuswithout local treatment (according to mRECIST or RECIST 1.1 requirements;

4. Eastern Cooperative Oncology Group performance status (ECOG PS) 0-1

5. BCLC-C stage accompanied by tumor thrombosis-associated portal hypertension;

6. Newly diagnosed patients who have not received local or systemic therapy in thepast;

7. Expected survival period ≥ 3 months;

8. The functions of vital organs meet the following requirements (no blood components,cell growth factors and other corrective treatment drugs are allowed within 14 daysbefore the first administration): the absolute count of neutrophils≥1.5×10^9/L;Platelet ≥50×10^9/L; Hemoglobin ≥60 g/L; Serum albumin ≥28 g/L; Thyroid-stimulatinghormone (TSH)≤1×ULN (if abnormal, the levels of FT3 and FT4 should be examined atthe same time, if the levels of FT3 and FT4 are normal, they can be included in thegroup); 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;

9. Child-Pugh score ≤ 13 points;

10. Diagnosed with portal hypertension-related complications: Gastrointestinal bleeding;refractory or recurrent ascites; hepatic pleural effusion; portal vein tumorthrombus exceeds 50% of lumen area.

11. Non-surgical sterilization or female patients of childbearing age need to use amedically approved contraceptive method (such as an intrauterine device,contraceptive, or condom) during the study treatment period and within 3 monthsafter the end of the study treatment period; Female patients of childbearing age whoundergo surgical sterilization must be negative in serum or urine HCG within 72hours before enrollment in the study; and must be non-lactating; for male patientswhose partners are women of childbearing age, at the last time use effective methodsfor 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 achievethe purpose of immunosuppression (dose>10mg/day prednisone or other curativehormones), and continues to use it within 2 weeks before enrollment;

3. Severe allergic reaction to any compositions of donafenib tablets or contrast mediacontaining iodine ;

4. Central nervous system metastasis;

5. Patients who have received liver transplantation in the past;

6. Tumor thrombus beyond the portal vein range, such as hepatic vein, inferior venacava, right atrium, splenic vein, superior mesenteric vein;

7. Suffer from high blood pressure and cannot be well controlled by anti-hypertensivedrugs (systolic blood pressure ≥140 mmHg or diastolic blood pressure ≥90 mmHg);

8. Uncontrolled cardiac clinical symptoms or diseases, such as: NYHA level 2 or higherheart failure, unstable angina pectoris, myocardial infarction occurred within 1year, clinically significant supraventricular or ventricular arrhythmia requirestreatment or intervention , QTc>450ms (male); QTc>470ms (female); Abnormalcoagulation function (INR>2.0, PT>16s), have bleeding tendency or are receivingthrombolysis or anticoagulation therapy, and allow the preventive use of low-doseaspirin and low molecular heparin;

9. Child-Pugh score >13 points;

10. Arterial/venous thrombosis events that occurred within 6 months beforerandomization, such as cerebrovascular accidents (including temporary ischemicattacks, cerebral hemorrhage, cerebral infarction), deep vein thrombosis, andpulmonary embolism;

11. Known genetic or acquired bleeding and thrombotic tendency (such as hemophiliapatients, coagulation dysfunction, thrombocytopenia, etc.);

12. Urine routine test showed urine protein ≥ ++ and confirmed 24-hour urine proteincontent> 1.0 g;

13. The patient has active infection, fever of unknown origin within 7 days beforemedication ≥38.5℃, or baseline white blood cell count >15×109/L;

14. Patients with congenital or acquired immune deficiencies (such as HIV-infectedpersons);

15. Moderate to severe pulmonary hypertension, pulmonary artery pressure was assessed byultrasound >40mmHg；

16. The patient suffered from other malignant tumors in the past 3 years or at the sametime (except for cured skin basal cell carcinoma and cervical carcinoma in situ);

17. The patient has previously received other anti-PD-1 antibody therapy or otherimmunotherapy against PD-1/PD-L1, or has previously received apatinib therapy;

18. According to the judgment of the investigator, the patient has other factors thatmay 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 other abnormalities which may affect theefficacy and/or safety of patients.