Hepatocellular carcinoma (HCC) remains a leading cause of cancer mortality and arises predominantly in cirrhotic livers, making prognosis and treatment response highly dependent on hepatic reserve and comorbidity. With multiple first-line immunotherapy and anti-VEGF based regimens, real-world decision making requires individualized selection integrating multiple patient related factors including liver function, bleeding risk, cardiovascular disease, and treatment feasibility among others. We reviewed pivotal first-line systemic therapy trials, complemented by key real-world cohorts evaluating outcomes in underrepresented populations. A targeted literature search was undertaken using PubMed/Medline and major oncology/hepatology meeting proceedings to identify prospective trials, guideline statements, and representative real-world studies focused on patient-level prognostic factors (Child-Pugh, ALBI), portal hypertension/varices, portal vein tumor thrombosis, cardiovascular risk, autoimmune disease, and transplant settings. We synthesize these data into a pragmatic framework to guide personalized regimen selection and improve prognostication in advanced HCC.
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Syed et al. (2026) studied this question.
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