Prospects for clinical translation of histotripsy in liver applications: a systematic review based on preclinical studies

Abstract

Background: Histotripsy, an ablation method relying on acoustic cavitation, is characterized by its non-thermal, non-ionizing, and non-invasive properties. It has the advantages of tissue selectivity, real-time visualization, and precise ablation. Among the clinical applications of histotripsy, its use in the treatment of liver cancer is the most promising. This review aimed to synthesize preclinical evidence and provide a comprehensive evaluation of histotripsy in the treatment of liver disease. Methods: PubMed, Embase, and Cochrane Library were searched from database inception to October 15, 2024 to retrieve relevant articles. The Systematic Review Centre for Laboratory Animal Experimentation risk of bias tool was used to assess study quality, and RevMan 5.4 was used to conduct the statistical analyses. Results: In total, 30 animal studies, comprising 25 in vivo and five ex vivo liver studies were included in this review on the application of histotripsy in the treatment of liver disease. In the feasibility research, 97% (96/99) of cases achieved precise ablation with minimal adverse effects (AEs), such as venous thrombosis and local tissue damage. In the rat liver cancer studies, all cases (9/9) who underwent complete ablation achieved 12-week survival. In the partial ablation group, 80% (12/15) achieved effective tumor burden reduction, while 20% (3/15) exhibited local tumor progression. Additionally, while no liver metastases were observed in the partial ablation group, liver metastases were observed in 64.71% (11/17) of the control group. In murine studies, histotripsy not only induced local tumor growth arrest but also triggered abscopal anti-tumor immune effects, manifested by the inhibition of contralateral tumor growth. Boiling histotripsy (BH) treatment of liver fibrosis reduced fibrosis scores and promoted hepatocyte regeneration. In cell therapy, the transplanted hepatocytes proliferated and integrated into the recipient livers. Conclusions: Histotripsy, a promising localized liver ablation method, is safe, targeted, and effective. It can precisely target and ablate tumor or fibrotic tissue through mechanical effects while preserving vital anatomical structures. Additionally, it can stimulate the immune system, inhibiting tumor growth and metastases.