Immune Checkpoint Therapy vs Target Therapy in Reducing Serum HBsAg Levels in Patients With HBsAg+ Advanced Stage HCC

Inclusion Criteria: 1. HBsAg positive with serum HBsAg levels ≥ 2 log IU/ml 2. Age ≥ 18 years old on the day of consent 3. Capable of understanding and complying with the protocol requirements and signed informed consent 4. Documented histological or cytological diagnosis of HCC within 1 year 5. Barcelona Clinic Liver Cancer (BCLC) stage B (that is not eligible for locoregional therapy) or stage C 6. Child-Pugh Score class A or B 7. ECOG performance status of 0 or 1 at enrollment. 8. Treated with either entecavir or tenofovir or TAF before initiation of anti-PDL1 or TKI 9. At least 1 measurable lesion, not previously irradiated, that can be accurately measured at baseline as ≥10 mm in the longest diameter (except lymph nodes, which must have a short axis ≥15 mm) with computerized tomography (CT) or magnetic resonance imaging (MRI), and that is suitable for accurate repeated measurements as per RECIST 1.1 guidelines. A lesion which progressed after previous ablation or TACE could be measurable if it meets these criteria 10. Adequate organ and marrow function, as defined below. Criteria "a," "b," "c," and "f" cannot be met with transfusions, infusions, or growth factor support administered within 14 days of starting the first dose. 1. Hemoglobin ≥9 g/dL 2. Absolute neutrophil count ≥1000/μL 3. Platelet count ≥75000/μL 4. Total bilirubin (TBL) ≤2.0× upper limit of normal (ULN) 5. AST and ALT ≤5×ULN 6. Albumin ≥2.8 g/dL 7. International normalized ratio (INR) ≤1.6 8. Calculated creatinine clearance ≥50 mL/minute as determined by Cockcroft-Gault (using actual body weight) or 24-hour urine creatinine clearance Exclusion Criteria: 1. Fibrolamellar carcinoma or mixed hepatocellular cholangiocarcinoma 2. Radiation therapy within 4 weeks (2 weeks for radiation for bone metastases) or radionuclide treatment (eg, I-131 or Y-90) within 6 weeks of starting treatment. Subject is excluded if there are any clinically relevant ongoing complications from prior radiation therapy 3. Prior interferon treatment 4. Concomitant anticoagulation, at therapeutic doses, with anticoagulants such as warfarin or warfarin-related agents, low molecular weight heparin (LMWH), thrombin or coagulation factor X (FXa) inhibitors, or antiplatelet agents (eg, clopidogrel). Low-dose aspirin for cardioprotection (per local applicable guidelines), low-dose warfarin (≤ 1 mg/day), and low-dose LMWH are permitted. 5. The subject has uncontrolled, significant intercurrent or recent illness including, but not limited to, the following conditions: a. Cardiovascular disorders including i. Symptomatic congestive heart failure, unstable angina pectoris, or serious cardiac arrhythmias ii. Uncontrolled hypertension defined as sustained BP \> 150 mm Hg systolic, or \> 100 mm Hg diastolic despite optimal antihypertensive treatment iii. Stroke (including TIA), myocardial infarction, or other ischemic event within 6 months before starting treatment iv. Thromboembolic event within 3 months before starting treatment. Subjects with thromboses of portal/hepatic vasculature attributed to underlying liver disease and/or liver tumor are eligible b. Gastrointestinal (GI) disorders including those associated with a high risk of perforation or fistula formation: i. Tumors invading the GI tract, active peptic ulcer disease, inflammatory bowel disease, diverticulitis, cholecystitis, symptomatic cholangitis or appendicitis, acute pancreatitis or acute obstruction of the pancreatic duct or common bile duct, or gastric outlet obstruction ii. Abdominal fistula, GI perforation, bowel obstruction, intra-abdominal abscess within 6 months before starting treatment, Note: Complete healing of an intra-abdominal abscess must be confirmed prior to starting treatment c. Major surgery within 2 months before starting treatment. Complete healing from major surgery must have occurred 1 month before starting treatment. Complete healing from minor surgery (eg, simple excision, tooth extraction) must have occurred at least 7 days before starting treatment. Subjects with clinically relevant complications from prior surgery are not eligible d. Cavitating pulmonary lesion(s) or endobronchial disease e. Lesion invading a major blood vessel (eg, pulmonary artery or aorta) f. Clinically significant bleeding risk including the following within 3 months of starting treatment: hematuria, hematemesis, hemoptysis of \>0.5 teaspoon (\>2.5 mL) of red blood, or other signs indicative of pulmonary hemorrhage, or history of other significant bleeding if not due to reversible external factors g. Other clinically significant disorders such as: i. known infection with human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS)-related illness requiring systemic treatment ii. Serious non-healing wound/ulcer/bone fracture iii. Malabsorption syndrome iv. Uncompensated/symptomatic hypothyroidism v. Requirement for hemodialysis or peritoneal dialysis 6. Subjects with untreated or incompletely treated varices with bleeding or high risk for bleeding are excluded with the following clarification: subjects with history of prior variceal bleeding must have been treated with adequate endoscopic therapy without any evidence of recurrent bleeding for at least 6 months prior to study entry and must be stable on optimal medical management (e.g. non-selective beta blocker, proton pump inhibitor) at study entry. 7. Moderate or severe ascites 8. Corrected QT interval calculated by the Fridericia formula (QTcF) \> 500 ms within 7 days before starting treatment Note: If the QTcF is \> 500 ms in first ECG, a total of 3 ECGs should be performed. If the average of these 3 consecutive results for QTcF is ≤ 500 ms, the subject meets eligibility in this regard. 9. Inability to swallow tablets 10. Previously identified allergy or hypersensitivity to components of the study treatment formulations 11. Pregnant or lactating females 12. Diagnosis of another malignancy within 2 years before starting treatment, except for superficial skin cancers, or localized, low-grade tumors deemed cured and not treated with systemic therapy