Abstract
Liver cancer encompasses both primary and secondary malignancies, each carrying unique diagnostic and therapeutic challenges. The goals of conventional liver-directed treatments, including radiofrequency ablation, microwave ablation, and stereotactic body radiotherapy, are local tumor control and improved survival outcomes. However, these treatments are limited by the heat-sink effect, incomplete ablation around vascular structures, and risk of collateral tissue injury. These limitations have prompted the exploration of alternative, non-thermal, and minimally invasive options. Histotripsy is a novel ultrasound-based technique that uses focused mechanical cavitation, rather than heat, to fragment tumor tissue, while preserving surrounding bile ducts and blood vessels. Preclinical and early clinical data, including the THERESA and HOPE4LIVER trials, have demonstrated histotripsy's feasibility, safety, and precision, confirming its ability to generate sharply demarcated ablation zones with minimal complications. Without thermal injury, histotripsy offers a vessel-sparing, non-ionizing, and repeatable treatment alternative, especially for patients with lesions adjacent to critical structures or those not suitable for resection or heat-based ablation. This review summarizes current evidence, principles, and translational insights of histotripsy as a promising non-thermal ablative technology in the treatment of hepatic malignancies and highlights its potential role as a future standard in image-guided liver therapy.