Different First-line Immunotherapy for Advancer Hepatocellular Carcinoma: A Prospective Observational Study on Efficacy and Immune Microenvironment

To evaluate the efficacy and immune microenvironment changes in advanced hepatocellular carcinoma (HCC) patients receiving different first-line immunotherapy.

This is a prospective, non-interventional, observational study evaluating the efficacy and immune microenvironment changes in advanced hepatocellular carcinoma (HCC) patients receiving different first-line immunotherapy, including anti-PD1+anti-VEGF, anti-PD1+TKI and anti-PD1+anti-CTLA4. The primary endpoint is objective response rate (ORR), with secondary endpoints including disease control rate (DCR), duration of response (DOR), time to response (TTR), progression-free survival (PFS), overall survival (OS), and immune profiling of tumor tissue and peripheral blood before and after treatment.

Inclusion Criteria: * Age ≥ 18 years at time of study entry. * Barcelona Clinic Liver Cancer stage C, or stage B not amenable to curative or locoregional therapies. * HCC confirmed by radiology, histology or cytology. * No prior systemic therapy for HCC. * At least one measurable site of disease as defined by RECIST1.1criteria with spiral CT scan or MRI. * Child-Pugh scores 5-7, performance status (PS) ≤ 2 (ECOG scale). * Adequate organ function: * ANC ≥1.5 × 10⁹/L, platelets ≥100 × 10⁹/L, hemoglobin ≥9 g/dL. * Total bilirubin ≤1.5 × ULN, AST/ALT ≤3 × ULN (≤5 × ULN if liver metastases). * Creatinine ≤1.5 × ULN or CrCl ≥60 mL/min. * Willing to provide archival/fresh tumor tissue and peripheral blood samples. * Signed informed consent. Exclusion Criteria: * Prior systemic therapy for HCC * Active autoimmune disease requiring immunosuppression. * Active infection requiring IV antibiotics. * HIV-positive or active HBV/HCV infection (HBsAg+ with HBV DNA ≥2000 IU/mL; HCV RNA+). * Symptomatic CNS metastases. * Pregnancy/lactation. * Any condition compromising protocol compliance or data interpretation per investigator.