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The therapeutic landscape of advanced hepatocellular carcinoma (HCC) has undergone a paradigm shift with the advent of immune checkpoint blockade (ICB). Since the landmark success of atezolizumab plus bevacizumab in the IMbrave150 trial, immunotherapy has become the standard of care for advanced HCC. Despite these advances, a central unresolved question continues to shape the field: does HCC aetiology influence responsiveness or prognosis following immunotherapy?