Histotripsy for Hepatocellular Carcinoma in Asia-Pacific: Current Evidence, Evidence Gaps, and Future Research Priorities

Background: Histotripsy is a non-thermal focused-ultrasound ablation technology that produces mechanical tissue fractionation through controlled acoustic cavitation. In hepatocellular carcinoma (HCC), its relevance remains investigational, particularly in settings where conventional thermal ablation may be constrained by heat-sink effects, vascular or biliary proximity, limited hepatic reserve, or the need for repeated local therapy. This review evaluates the evidence without assuming an established clinical role. Methods: We performed a structured narrative review with systematic literature identification and evidence classification. The structured core search covered PubMed/MEDLINE, Scopus, Embase, and Google Scholar from database inception through February 2026; a targeted update through 20 September 2026 was used to identify newly published clinical studies, safety reports, and reviews. Evidence was classified as direct HCC, mixed liver-tumour, non-HCC clinical extrapolation, or preclinical/mechanistic evidence. Results: Evidence remains early-stage and heterogeneous. #HOPE4LIVER reported 95.5% technical success and 6.8% major complications in mixed primary and metastatic liver-tumour cohorts, with incomplete HCC-specific outcome reporting. The Hong Kong prospective cohort included 19 patients with HCC, all Child-Pugh A, and reported 95% technical success, 82.5% complete response at 1 month, and no grade III or higher complications. Real-world reports also document vascular injury, haemorrhage, and pseudoaneurysm, underscoring that relative resistance of collagen-rich structures should not be interpreted as proven vascular or biliary safety. Conclusion: Histotripsy should be regarded as an investigational non-thermal ablation technology for HCC. Current data support technical feasibility and preliminary clinical signals, but not superiority, equivalence, or guideline-defined positioning relative to established therapies. HCC-specific prospective cohorts, standardized safety reporting, long-term oncological outcomes, and comparative studies are required.