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

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.