Microvascular Invasion for Guiding Treatment of Barcelona Clinic Liver Cancer Stage B Hepatocellular Carcinoma

Inclusion Criteria:

1. Age 18-75 years;
2. BCLC stage B HCC;
3. Received no previous anti-cancer treatment;
4. At least 1 measurable intrahepatic lesion based on the Response Evaluation Criteria in Solid Tumors criteria (RECIST) 1.1;
5. Adequate hematological, liver, renal function:

   1. absolute neutrophil count ≥ 1.5×109/L;
   2. platelet count ≥ 100×109/L;
   3. hemoglobin concentration ≥ 90 g/L;
   4. albumin ≥ 28 g/L;
   5. total bilirubin \< 1.5 times the upper limit of normal;
   6. alanine aminotransferase and aspartate aminotransferase \< 5 times the upper limit of normal;
   7. blood urea nitrogen and serum creatinine concentration \< 1.5 times the upper limit of the normal range or less and creatinine clearance rate ≥ 45 mL/min;
6. Life expectancy of at least 3 months.

Exclusion Criteria:

1. Acute or chronic active hepatitis B (HBV) or C (HCV) infection with HBV-DNA \> 2000 IU/ml or 104 copies/ml; hepatitis C virus RNA \> 103 copies/ml; HBsAg and anti-HCV antibody positive at the same time. Those who are below the above criteria after nucleoside based antiviral therapy may be enrolled;
2. Life-threatening bleeding event within the past 3 months, including the need for blood transfusion, surgical or local treatment, or continuous medication;
3. History of previous arterial or venous thromboembolic events within the past 6 months, including myocardial infarction, unstable angina, cerebrovascular accident or transient ischemic attack, pulmonary artery embolism, deep vein thrombosis, or any other serious thromboembolism;
4. Use of aspirin (\>325 mg/day) or other drugs known to inhibit platelet function such as dipyridamole or clopidogrel for 10 consecutive days within 2 weeks prior to enrollment;
5. Uncontrolled hypertension, systolic blood pressure \> 140 mmHg or diastolic blood pressure \> 90 mmHg after optimal medical treatment, history of hypertensive crisis or hypertensive encephalopathy;
6. Symptomatic congestive heart failure (New York Heart Association class II-IV); Symptomatic or poorly controlled arrhythmias; History of congenital long QT syndrome or corrected QT (QTc) \> 500 ms at screening;
7. Diagnosis of other malignant tumors within 5 years prior to enrollment;
8. Pregnant or lactating women or subjects planning to have a baby during the study period;
9. Accompanied with other uncontrolled co-morbidities;
10. Co-infection with HIV, known syphilis infection requiring treatment.