Hepatic Arterial Infusion Chemotherapy for Advanced Hepatocellular Carcinoma in the Era of Systemic Therapies (2020-2025).

Background: Management of advanced hepatocellular carcinoma (HCC) has evolved rapidly in recent years. Following the publication of the IMbrave150 study in 2020, which established atezolizumab-bevacizumab as first-line therapy, multiple systemic therapies have been approved and incorporated into global clinical guidelines. However, outcomes remain suboptimal in high-risk cases (e.g., extensive tumor burden, macrovascular invasion). Summary: This review examines the role of hepatic arterial infusion chemotherapy (HAIC) in the context of modern systemic therapy for advanced HCC. A literature search (2020-2025) was conducted employing a PICO framework (Patients: advanced HCC; Intervention: HAIC; Comparison: any or no alternative therapy; Outcomes: efficacy and safety). HAIC is a regional chemotherapy approach delivered via the hepatic artery, allowing high intratumoral drug concentration with manageable systemic toxicity. It is popularly used in East Asia and has demonstrated promising survival benefits in patients with portal vein tumor thrombosis (PVTT) or large tumors - subgroups where systemic therapies or transarterial chemoembolization frequently fail. HAIC is an integral modality for advanced HCC, especially for patients with extensive liver tumors or PVTT. It provides critical bridge-to-curative options by downsizing tumors and improving systemic treatment effects. To integrate HAIC into global practice, standardization of techniques, patient selection, biomarkers, and confirmatory trials in non-Asian populations is needed. HAIC can change the standard of care by improving outcomes in patient subsets poorly served by current therapies. Key Messages: Paradigm shift to synergy: HAIC has transitioned from a palliative locoregional tool to a central pillar of "triple therapy" (HAIC + tyrosine kinase inhibitor + immune checkpoint inhibitor), leveraging immunogenic cell death to improve systemic treatment efficacy. Superiority in high-risk subsets: This modality demonstrates exceptional survival benefits in patients with high tumor burden and major PVTT (Vp4 PVTT) - subgroups where standard systemic monotherapies frequently fail. A bridge to cure: HAIC-based combination regimens significantly increase conversion-to-surgery rates by inducing rapid tumor necrosis and downstaging, thereby providing curative opportunities for initially unresectable patients. Global standardization needs: Future adoption relies on international consensus to standardize delivery protocols and biomarker-driven model validation for precise patient selection.