Evaluation of Efficacy and Safety of Immune Check Point Inhibitors in Hepatocellular Carcinoma Patients in Ain Shams University Hospitals

Inclusion Criteria:

* Age ≥ 18.
* Hepatocellular carcinoma based on histological diagnosis or the typical findings on radiological imaging including enhanced dynamic computed tomography (CT) and/or dynamic magnetic resonance imaging (MRI).
* ECOG Performance status of 0 or 1
* Patients with Child-Pugh class A
* BCLC stage B with diffuse, infiltrative, or extensive bilobar involvement
* BCLC stage B with tumor progression after failure of TACE
* BCLC stage C
* No prior systemic therapy for HCC
* Additional eligibility criteria; Hb ≥ 9 g/dl, platelets ≥ 75x10%/1, ANC ≥ 1.5 x10% for Atezolizumab/bevacizumab and ANC ≥ 1x10%1 for Durvalumab/Tremilimumab, INR ≤ 2, albumin ≥ 2.8 g/dl, total bilirubin

  ≤ 3 mg/dl, AST and ALT ≤ 5 x ULN, creatinine clearance ≥ 50 ml/min
* Additional criteria for Atezolizumab/Bevacizumab; upper endoscopy showing no risky high grade esophageal varices (within 6 months of first dose) unless adequately managed

Exclusion Criteria:

* Performance status ≥ 2
* Patients with Child-Pugh class B or C
* BCLC stage A or D
* Active tuberculosis or active human immunodeficiency virus (HIV) infection
* HCV or HBV infection except if; HBV DNA \< 500 IU/ml or started anti- HBV treatment for a minimum of 14 days prior to first dose
* Severe infection requiring hospitalization within 4 weeks prior to first dose
* History of allogenic stem cell or solid organ transplant
* Treatment with systemic immunostimulatory or immunosuppressive medication
* Active and history of autoimmune disease or immune deficiency
* Receiving a live, attenuated vaccine within 4 weeks prior to first dose
* History of idiopathic pulmonary fibrosis, or evidence of active pneumonitis
* Central nervous system metastases
* Symptomatic hypercalcemia (ionized calcium \> 1.5 mmol/1 (6 mg/dl), calcium \> 12 mg/dl, or corrected serum calcium \> ULN)
* History of severe allergic anaphylactic reactions to chimeric or humanized antibodies or fusion proteins
* Prior history of hypertensive crisis or hypertensive encephalopathy
* Cardiac conditions, such as severe heart failure, unstable angina, recent myocardial infarction, severe arrhythmias
* Evidence of bleeding diathesis or coagulopathy Special for atezolizumab + bevacizumab
* Risky esophageal or gastric varies unless adequately managed
* Severe portal hypertensive gastropathy which is associated with decline in hemoglobin, uniess controlled
* Severe proteinuria ≥ 3.5 g/24 hrs or by dipstick 4+ proteinuria, according to CTCAE. Special for tremelimumab + durvalumab
* Main portal vein tumor thrombosis