Testing Immunotherapy for Patients With Liver Cancer and Moderately Altered Liver Functions

Inclusion Criteria: 1. Age ≥18 years old 2. Patient presenting with histologically-proven Hepatocellular Carcinoma (HCC), or HCC defined by typical imaging findings (EASL criteria), if no biopsy could be performed safely 3. Pretreated or not by tyrosine kinase inhibitors (e.g., sorafenib, lenvatinib, regorafenib, cabozantinib) 4. Child-Pugh B cirrhosis 5. ALBI (Albumin-Bilirubin) grade 1 or 2 6. BCLC (Barcelona Clinic Liver Cancer Group) B or C 7. Availability of biopsy specimen at study enrolment (taken within 3 months of enrolment with the exception of cases where biopsy could not be performed safely) 8. ECOG Performance status ≤2 9. Adequate organ function as indicated by the following laboratory values: 1. Patients must not have required a blood transfusion or growth factor support ≤14 days before sample collection at screening for the following: * Absolute neutrophil count (ANC) ≥1.5 x 10⁹/L * Platelets ≥75 x 10⁹/L * Hemoglobin ≥90 g/L 2. Serum creatinine ≤1.5 x upper limit of normal (ULN) or estimated Glomerular Filtration Rate ≥60 mL/min/1.73 m² 3. Serum total bilirubin ≤3 mg/dL 4. Liver function: ASAT and ALAT ≤5 ULN, albumin \>2.0 g/dL 10. Presence of measurable and evaluable disease according to RECIST v1.1 11. Women of childbearing potential must be willing to use a highly effective method of birth control for the duration of the study, and ≥120 days after the last dose of tislelizumab, and have a negative urine or serum pregnancy test ≤7 days of first dose of study drug. In case of a urine pregnancy test, it must be a highly sensitive urine pregnancy test 12. Non-sterile males must be willing to use a highly effective method of birth control for the duration of the study and for ≥120 days after the last dose of tislelizumab. A sterile male is defined as one for whom azoospermia has been previously demonstrated in a semen sample examination as definitive evidence of infertility. Males with known "low sperm counts" (consistent with "sub-fertility") are not to be considered sterile for purposes of this study 13. Patients must have provided consent for the study by signing and dating a written informed consent form prior to any study specific procedures, sampling, or analyses. When the patient is physically unable to give their written consent, a trusted person of their choice, independent from the investigator or the sponsor, can confirm in writing the patient's consent 14. Patient consent to the use of their collected tumour specimen, as well as blood samples as detailed in the protocol for future scientific research which includes but not limited to DNA, RNA, and proteinbased biomarker detection 15. Patient affiliated to a social security regimen 16. Men and women patients must consent to not donate or bank sperm or ova during treatment and for 120 days after treatment stop Exclusion Criteria: 1. More than 50% of the liver is affected by the HCC (according to investigators evaluation) 2. Fibrolamellar HCC, sarcomatoid HCC, or mixed cholangiocarcinoma and HCC 3. Previous treatment with immunotherapy (anti-PD-1, anti-PD-L1, or anti-CTLA-4 agents) 4. History of active autoimmune disease. Note: Patients with the following diseases are not excluded and may proceed to further screening: 1. Type I diabetes 2. Hypothyroidism (provided it is managed with hormone replacement therapy only) 3. Controlled celiac disease 4. Skin diseases not requiring systemic treatment (e.g., vitiligo, psoriasis, alopecia) 5. Any other disease that is not expected to recur in the absence of external triggering factors 5. History of interstitial lung disease, non-infectious pneumonitis or uncontrolled diseases including pulmonary fibrosis, acute lung diseases 6. Any of the following cardiovascular risk factors: 1. Cardiac chest pain, defined as moderate pain that limits instrumental activities of daily living, ≤28 days before first dose of study drug 2. Pulmonary embolism ≤28 days before first dose of study drug 3. Any history of acute myocardial infarction ≤6 months before first dose of study drug 4. Any history of heart failure meeting New York Heart Association (NYHA) Classification III or IV ≤6 months before first dose of study drug 5. Any event of ventricular arrhythmia ≥ Grade 2 in severity ≤6 months before first dose of study drug 6. Any history of cerebrovascular accident ≤ 6 months before first dose of study drug 7. Uncontrolled hypertension: systolic pressure ≥160 mmHg or diastolic pressure ≥100 mmHg despite anti-hypertension medications before first dose of drug 8. Any episode of syncope or seizure before first dose of study drug 7. Patients with untreated chronic hepatitis B or chronic hepatitis B virus (HBV) carriers whose HBV DNA is \>500 IU/mL or patients with active hepatitis C virus (HCV) should be excluded. Note: Inactive hepatitis B surface antigen (HBsAg) carriers, treated and stable hepatitis B (HBV DNA \<500 IU/mL), and cured hepatitis C patients can be enrolled 8. Known primary immunodeficiency or active HIV 9. Immunosuppression, including subjects with a condition requiring systemic treatment with either corticosteroids (\>10 mg/day prednisone equivalent) ≤14 days before inclusion. Note: Patients who are currently or have previously been on any of the following steroid regimens are not excluded: 1. Adrenal replacement steroid (dose ≤10 mg daily of prednisone or equivalent) 2. Topical, ocular, intra-articular, intranasal, or inhaled corticosteroid with minimal systemic absorption 3. Short course (≤7 days) of corticosteroid prescribed prophylactically (e.g., for contrast dye allergy) or for the treatment of a non-autoimmune condition (e.g., delayed-type hypersensitivity reaction caused by contact allergen) 10. Live vaccine within 4 weeks of first dose of study drug. Note: Seasonal vaccines for influenza are generally inactivated vaccines and Covid vaccination with non-live vaccine are allowed. Intranasal vaccines are live vaccines, and are not allowed 11. Transplanted liver, or patient with intent for transplantation 12. Received locoregional therapy to the liver (TACE, transcatheter embolization, hepatic arterial infusion, radiation, radioembolization or ablation) in the 4 weeks before inclusion 13. Prior malignancy active within the previous 3 years of inclusion except for locally curable cancers considered cured or successfully resected, such as basal or squamous cell skin cancers, superficial bladder cancer, or gastric cancers, or carcinoma in situ of the prostate, cervix, or breast carcinomas. Any oncological concomitant treatment are not allowed during the treatment period 14. Has received any herbal medicine used to control cancer with immunostimulant properties that may interfere with liver function within 14 days of the first study drug administration 15. Pregnant woman or breast-feeding women or patient with no adequate contraception 16. Participation in another therapeutic trial within the 30 days prior to study inclusion 17. Patients deprived of their liberty or under protective custody or guardianship 18. Patients unable to adhere to the protocol for geographical, social, or psychological reasons 19. Patients eligible for treatment by TACE or SIRT are not allowed