Anti Angiogenic Agents for Advanced Hepatocellular Carcinoma Induce Liver Atrophy summary

This PACUPod episode examines Wake et al.'s retrospective cohort study of 73 patients with advanced hepatocellular carcinoma starting first-line systemic therapy (atezolizumab-bevacizumab or lenvatinib). The study investigates changes in liver parenchyma volume beyond tumor shrinkage. Findings show substantial non-tumoral liver volume loss by week 8, with ongoing reduction to week 16, and a greater degree of liver atrophy observed with lenvatinib compared to atezolizumab-bevacizumab. Importantly, liver volume decline occurred independently of tumor response, underscoring the need for vigilant liver function monitoring, potential dose adjustments, and careful therapy selection—especially for patients with borderline liver function. The episode also discusses limitations (retrospective design, relatively stable cohort), implications for incorporating liver volumetry into routine monitoring, and directions for future prospective research to determine whether liver atrophy predicts hepatic decompensation or survival. Clinician and pharmacist considerations include drug interactions affecting liver injury risk (notably lenvatinib and CYP3A4) and the potential impact of combining systemic anti-angiogenics with local therapies like TACE.