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

Introduction

Liver cancer is the sixth most common malignancy and the third leading cause of cancer-related death worldwide (1). The liver is also a common metastatic site for other tumors, including colorectal, pancreatic, and breast cancers. Notably, at least 25–50% of patients diagnosed with colorectal cancer will develop liver metastases (2). Similarly, liver metastases account for 70–80% of pancreatic cancer metastases (3).

Local treatments have shown comparable efficacy to surgery in the treatment of liver metastases patients. These therapies are mainly aimed at patients with advanced cancer who are unsuitable for surgical interventions. They can control the progression of tumors and prolong the survival of patients in combination with systemic therapy, providing an opportunity for liver transplantation. However, existing local liver treatments have some limitations. Thermal ablation methods, including microwave ablation (MWA), radiofrequency ablation (RFA), and high-intensity focused ultrasound (HIFU), are subject to the “heat sink” effect, which can lead to incomplete tumor treatment and cause thermal damage (4,5). Similarly, cryoablation, a local ablation method that destroys tissue by freezing, carries the risk of cryoshock and liver function impairment (6,7).

Non-invasive ultrasound therapy comprises multiple modalities. Histotripsy, as a non-invasive ultrasound ablation method relying on acoustic cavitation, is characterized by its non-thermal, non-invasive, and non-ionizing properties (8). It produces precise lesions without thermal damage to surrounding tissues (9-13). Histotripsy can be further categorized into two main types: cavitational histotripsy (CH) and boiling histotripsy (BH). CH employs microsecond-long pulse ultrasound, characterized by a peak negative pressure (P⁻) >20 MPa and a duty cycle ≤1% (14). A cavitation cloud can be produced through two CH methods. Intrinsic threshold CH forms a bubble cloud when P⁻ directly surpasses the intrinsic threshold and leads to inertial cavitation (15). Shock-scattering CH uses pulses of 3–20 cycles with a lower P⁻ than the intrinsic threshold. It activates existing cavitation nuclei into microbubbles in 1–2 cycles (14). The peak amplitude of the ultrasonic shockwave is amplified in nonlinear acoustic propagation, and the reflection from the microbubble reverses the shockwave’s phase. When this elevated pressure surpasses the intrinsic threshold, a cavitation cloud forms (16). BH uses millisecond-long pulse ultrasound, with a P⁻ ranging from 10–15 MPa and a duty cycle of 1–2% (14). Local high shockwave energy heats tissue and produces boiling vapor bubbles. The interaction between the boiling bubbles and the incident shocks results in tissue liquefaction (17).

Histotripsy has been explored for many diseases in preclinical research, such as liver (18,19), kidney (20,21), pancreas (22,23), brain (24,25), and bone (26,27) diseases, as well as blood clots (28,29), and abscesses (30). Among the applications of histotripsy, its use in the treatment of liver cancer is the most promising. Early studies largely employed porcine liver models to assess the feasibility of histotripsy and explored its tissue selectivity (11-13,31-34). More recent studies have explored a wider range of areas, including the long-term healing response, the immune mechanism, and aberration correction methods. However, variations in histotripsy methods and devices across studies complicate the direct comparison of their respective findings.

The use of histotripsy in liver applications has entered the clinical stage (35-37). Figure 1 illustrates the application of histotripsy in liver tumor therapy, showcasing its potential in treating both primary and metastatic liver cancers. The HistoSonics Edison^® System (Plymouth, MN, USA) has recently been authorized by the United States Food and Drug Administration (FDA) for the treatment of liver tumors (36), and to date, more than 1,000 patients have been treated. This device operates on the principle of CH (35). It uses a 700-kHz therapeutic transducer to emit a pulse sequence (pulse width: <20 µsec, and duty cycle: <1%), generating a high P⁻ (>10 MPa) at the focal point (35,36). The therapy transducer is equipped with a coaxially aligned diagnostic ultrasound probe, enabling the real-time visualization of the hyperechoic cavitation clouds generated at the focal point, as well as the hypoechoic cavities following the liquefaction of the target tumor (36,37).

Figure 1 Application of histotripsy in liver tumor therapy. (A) Primary hepatic carcinoma. (B) Metastatic hepatic carcinoma. The dashed box highlights the process of tumor cell destruction by cavitation bubbles, illustrating the mechanical fractionation effect of histotripsy. Created in BioRender (Yiyi Y, 2025). Available online: https://BioRender.com/e9yxp59.

Current reviews have demonstrated the broad therapeutic potential of histotripsy across various malignancies, including brain tumors, pancreatic cancer, and breast cancer (38,39). These studies not only reveal the unique immune mechanism of histotripsy but also offer a combined treatment strategy with immune checkpoint inhibitors (40). In this study, we collected preclinical evidence on the use of histotripsy and performed a systematic review to provide the first comprehensive statistical evaluation of the use of histotripsy in the treatment of liver disease. We performed an in-depth assessment of histotripsy from the preclinical to clinical stages in the treatment of liver cancer, examining its safety, efficacy, adverse effects (AEs), immune responses, and healing process. Further, we examined the latest advances in potential therapeutic directions for histotripsy, including cell therapy and liver fibrosis. We present this article in accordance with the PRISMA reporting checklist (available at https://qims.amegroups.com/article/view/10.21037/qims-2025-1137/rc).

Methods

Search strategy

Three major databases (PubMed, Embase, and Cochrane Library) were searched from database inception to October 15, 2024 to retrieve relevant literature. The general architecture of the search strategy is summarized in Table 1.

Study selection and data extraction

Two researchers independently screened the articles. The inclusion criteria were as follows: (I) P (population): experimental animal studies with no species restriction, focusing on the liver; (II) I (intervention): any type of histotripsy; (III) O (outcome): clearly defined outcome indicators; and (IV) L (language): studies published in the English language. The exclusion criteria were as follows: (I) irrelevant studies; and/or (II) duplicate publications.

The following information for each study was independently extracted by the two researchers: first author, year of publication, subject type, sample size, survival outcome, ablation method, ablation parameters, and AEs.

Risk of bias

The quality of the included live animal studies was assessed by two investigators using the Systematic Review Centre for Laboratory Animal Experimentation’s risk of bias (SYRCLE’s RoB) tool (41). This tool includes 10 items and 22 sub-items related to performance bias (e.g., random housing and the blinding of participants and personnel), reporting bias (e.g., selective outcome reporting), selection bias (e.g., sequence generation, baseline characteristic, and allocation concealment), attrition bias (e.g., incomplete outcome data), detection bias (e.g., random outcome assessment, and outcome assessment blinding), and other biases (41). The assessment results were categorized as “unclear”, “low risk”, and “high risk”.

Statistical analysis

The data extracted from the included studies were entered into preset sheets (using Microsoft Excel). The categorical variables are presented as the absolute frequency and percentage. Due to the clinical and methodological heterogeneity of the included animal studies, quantitative analyses were difficult; thus, only qualitative analyses were performed.

Results

Data set

In total, 1,883 studies were identified in the initial search. After duplication removal, 1,346 studies remained. Additionally, 1,262 studies were excluded because of their unqualified titles and abstracts, and 54 studies were excluded after full-text screening because they did not meet the established criteria. Thus, ultimately, the qualitative research included 30 animal studies, comprising 25 in vivo studies (9,11-13,18-20,31-34,42-55) and five ex vivo liver studies (56-60) (Figure 2).

Figure 2 PRISMA flow diagram of the literature screening process.

Risk of bias assessment

The results of the methodological assessments of the 25 in vivo animal studies are presented in Figures 3,4. Among these studies, two were randomized controlled trials (46,47), but neither reported the specific randomization methods. Additionally, two studies had incomplete data, as they did not report the complete survival status of the experimental animals (44,51). The baseline was consistent in the study groups, and all studies had a low risk of reporting bias. None of the studies indicated that the experiments were conducted with allocation concealment and blinding. No trials reported on the blinding of the outcome evaluators, but this was deemed as a low risk of measurement bias because the outcomes were objective indicators. The five ex vivo animal studies included in this review were not assessed using the SYRCLE’s RoB tool, as it is not applicable to ex vivo studies. However, these studies showed that the sample sources were well defined with a clear organ origin and processing time (56-60). The data provided in these studies were comprehensive, and there was no evidence of selective reporting bias. Overall, the methodological quality of the 30 included studies was reliable and acceptable.

Figure 3 Risk of bias. Assessment based on the SYRCLE tool.

Figure 4 The methodological assessments of each study. “?”, unclear risk; “+”, low risk; “−”, high risk.

Characteristics of included studies

Preclinical studies of histotripsy have covered a diverse range of animal models. A total of 17 studies used porcine models, of which, 14 used live pigs (9-13,18-20,31-34,42,48), and three used ex vivo pig livers (56-58). Additionally, seven studies used rats (43,45,47,49,50,54,55), three used mice (44,51,53), one single study used rabbits (46), and two studies used bovine liver models (59,60).

Among the 14 in vivo porcine studies, two focused exclusively on aberration correction methods (42,48), while the remaining 12 studies assessed the feasibility of histotripsy and simulated the effects of human tissue ablation in 99 animals (9-13,18-20,31-34). Five studies used rodent animal tumor models to investigate tumor ablation effects and immune responses, of which, three used mouse models (44,51,53) and two used rat models (47,50). Additionally, two studies focused on cell therapy (55,58), and one study analyzed the treatment effects for hepatic fibrosis (43). Three other studies examined aberration correction methods with ex vivo livers (56,59,60). One study proposed a more precise ablation technique based on BH; that is, pressure-modulated shockwave histotripsy (PSH) (45). The specific characteristics of each preclinical study are detailed in Table 2.

Feasibility of histotripsy

Effects of ablation

A total of 99 samples were included in the technology feasibility studies. Precise ablation was achieved in 97% (96/99) of the cases, and the ablation zones were highly consistent with the predefined targets. The ablation areas exhibited characteristic homogeneous liquefactive necrosis with sharp boundaries (9-13,18-20,31-34). Histological analyses confirmed that these zones consisted of acellular eosinophilic material, nuclear debris, and hemorrhagic foci (10,11,19,20,33,34,57).

Histotripsy has differential destructive effects on different tissues. Hepatocytes are selectively destroyed, while collagen-rich structures such as vessels and bile ducts are generally preserved (10-13,18-20,31-34). Small-sized vessels (100–300 µm) are reduced and obliterated, while most medium-sized vessels (300 µm–1 mm) and bile ducts remain intact (13,31,32). Vessels larger than 1 mm are fully preserved in the treated areas (13,32). Real-time ultrasound images showed hyperechoic cavitation clouds during treatment, and hypoechoic cavities appeared following the procedure, with their size and location corresponding to the gross liquefaction areas (10-13,18,31-34).

Safety and efficacy evaluation

In general, histotripsy can safely and effectively ablate target tissues with minimal side effects. In rodent tumor models (47,50,53), the survival time of the subjects was prolonged significantly. Notably, 46.67% (7/15) of rats in the partial ablation group achieved tumor-free survival until the 12-week observational endpoint. Conversely, the survival time of the control groups ranged from 1.45±0.69 to 7.5±2.03 weeks (47,50). In another subcutaneous murine model of hepatocellular carcinoma (HCC), the ablated tumor volume was resorbed in 2–3 weeks. However, the residual tumor cells re-grew in 3–9 weeks, which can be attributed to the compromised immune system and incomplete treatment of subcutaneous tumors due to the lack of a treatment margin (53).

The AEs were summarized in 12 in vivo porcine model studies (9-13,18-20,31-34). However, it is not certain that all AE types were evaluated in every study. Thus, for each AE, the studies that reported the same AE were counted and summarized in subcategories, respectively. The specific details regarding the occurrence of AEs in each study are listed in Table 2. The AEs largely comprised venous thrombosis and localized tissue damage, most of which were transient and resolved spontaneously. Portal vein thrombosis was the most common type of thrombosis (27/36, 75%) (10,11,18,20,21), followed by hepatic vein thrombosis (8/24, 33.33%) (10,11,21). Local tissue injuries included microscopic vein wall rupture (12/22, 54.54%) (12), body wall injury (12/19, 63.15%) (11,18,31), mild pulmonary parenchymal injury (6/12, 50%) (10,18), diaphragmatic damage (3/14, 21.43%) (10,21), and hemorrhage from the gallbladder bed (1/6, 16.67%) (10). Of the subjects, 4.55% (1/22) showed transient vital sign change, manifested as a transient decrease in blood pressure and heart rate (12). More details and comprehensive information on the AEs are provided in Table 3.

Applications

Liver tumors

Preclinical studies in immunocompetent rat HCC models have demonstrated the efficacy of both complete and partial histotripsy ablation (47,50). Complete ablation (100% tumor volume + 2-mm margin) resulted in effective tumor burden reduction with all (9/9) animals surviving to the 12-week endpoint (50). Partial ablation (50–75% tumor volume) achieved similar therapeutic outcomes with the near-complete regression of the ablated tumor in 80% (12/15) of cases, while the remaining 20% (3/15) required euthanasia because they met the tumor endpoint criteria (25-mm maximum dimension) (47,50). Notably, two additional rats also underwent partial ablation and achieved tumor-free survival at 7 weeks [the experiment was terminated early because of coronavirus disease (COVID)]. No metastases were observed in either ablation group. Conversely, in the untreated control group, liver metastases developed in 64.71% (11/17) of the cases (47). Table 4 summarizes the efficacy of histotripsy in rat tumor models.

Histotripsy may also stimulate immune responses, potentially promoting the abscopal effects observed in murine models (44,51). In C57BL/6 mice bearing bilateral Hepa1-6 HCC tumors or B16F10 melanomas, partial histotripsy ablation (80–90% volume) at days 9–10 post-inoculation induced immediate growth arrest in both local and contralateral tumors, with some cases showing gradual regression (44,51). However, abscopal growth inhibition was not observed in contralateral discordant pathological tumors, suggesting that the abscopal effect might be antigen-specific (44).

Liver fibrosis and cell therapy

BH can mechanically fractionate liver fibrotic tissue. In a study by Joung et al. (43), liver fibrosis rats induced by thioacetamide (TAA) were treated with BH. The fibrosis scores in the treated lobes, including the penumbra, were significantly lower relative to those in the untreated lobes at both 21- and 90-day post-ablation. Additionally, the enhanced levels of hepatocyte-specific markers, such as asialoglycoprotein receptor 1 (ASGR1) and CD26, indicated hepatocyte regeneration (43).

Hepatocytes maintained metabolic activity and morphology in culture studies. Froghi et al. isolated an average of 61×10⁴ cells per mL of cell suspension in porcine liver cavities, and the live cell rate increased from 12% to 45% in 1 week (58). Liver cavities after ablation provide favorable environments for cell transplantation. Pahk et al. injected hepatocytes into liver cavities in Nagase albumin-free rat models. The transplanted hepatocytes proliferated and integrated into the recipient livers, leading to a recovery of plasma albumin level to 50% of the normal value (55).

Discussion

Histotripsy, a non-thermal focused ultrasound (FUS) therapy, has demonstrated significant potential in the treatment of liver disease due to its high precision and non-invasiveness. Preliminary findings from preclinical studies suggest that histotripsy can achieve safe and effective ablation and adequate treatment for tumor models with a good prognosis (38,39,61). However, there has been a lack of integrated data analysis in the field of liver treatments with histotripsy. To address this gap, we performed a systematic data analysis and provided a comprehensive summary of the findings of preclinical and clinical studies. This review also extended the study scope to include the technical advantages, technical concerns, AEs, and immune responses associated with histotripsy. To supply a reference for the clinical applications of histotripsy, PubMed, Embase, and Cochrane Library were searched to retrieve relevant studies published from database inception to 2024. Ultimately, 30 studies were included in the analysis.

Histotripsy harnesses the mechanical effect of acoustic cavitation for tumor ablation with minimal thermal damage, offering a new option for patients who cannot undergo conventional treatments such as hepatic resection. The first clinical case examined the use of histotripsy as a bridging therapy for patients with HCC before liver transplantation (62). Histotripsy has several potential advantages over other local ablation methods. Its non-invasive operations not only significantly reduce direct injury but also avoid the risks of infection and needle-track metastases. The mechanical effect of cavitation creates a therapeutic zone with a sharp boundary between fully liquefied lesions and intact surrounding tissues (9-13,18-20,31-34), rendering the ablation resistant to thermal diffusion and thus overcoming the “heat sink” limitation in perivascular tumors. Histotripsy also offers excellent tissue selectivity, allowing for safe ablation adjacent to crucial anatomical structures, such as bile ducts and blood vessels, without the risk of hemorrhage or bile leakage (32,34). However, clinicians should be aware of an important exception when adjusting the ablation strategy: if the target tissue has a higher mechanical strength than the critical structures, then they will not be preserved (63). Finally, real-time visualization allows dynamic monitoring during treatment. A study reported a severe body wall injury linked to a treatment that failed to produce a clear bubble cloud and deviated from the target area (11). Thus, the inability to produce a clear bubble cloud should be considered a contraindication for histotripsy (11).

In this study, we conducted the first comparative analysis of CH and BH, exploring their clinical applications and distinctive characteristics. Both BH and CH use mechanical effects produced by high-intensity negative pressure FUS, but their clinical translation and application scenarios differ slightly. CH generates near-spherical liquefactive necrosis with sharp boundaries and demonstrates higher technical maturity (11). The CH-based HistoSonics system has received FDA approval for liver tumor treatment. The first human trial (THERESA, NCT03741088) has suggested promising technical efficacy and safety—10/11 whole tumors with approximately 5-mm margins were successfully ablated without device-related adverse events (35). A multicenter study (HOPE4LIVER, NCT04572633, NCT04573881) enrolled 44 patients with 49 tumors, and reported a successful therapeutic technique in 42/44 cases (95%) within 36 hours of surgery (36,64). Further, long-term follow-up data revealed a 1-year local control rate of 63.4% by primary assessment and 90% by post-hoc analysis, with 1-year overall survival rates of 73.3% for patients with HCC and 48.6% for patients with liver metastases (37). The tumor involution rate at 1 year was 81.8%, and the treatment zone volume decreased by 96.4% (37). The current evidence suggests that CH may be a preferable ablation method for standardized tumor ablation protocols.

Conversely, BH produces tadpole-shaped lesions (45). While BH achieves effective liquefaction in central hepatic zones, its efficacy in peripheral ablation remains suboptimal, and the unexpected thermal effects may be a concern (31). A pilot study showed bruising and thermal injury in the fatty layer of the body wall in 70% (7/10) of cases, likely caused by acoustic attenuation in adipose tissue, which leads to pre-focal heating rather than inducing boiling (31). Nevertheless, BH has demonstrated unique value in liver therapies. In cell therapy, due to its tissue selectivity, BH preserves the extracellular matrix and vascular network, which are crucial for providing attachment sites for transplanted hepatocytes and facilitating the transport of oxygen and nutrients (55). Additionally, BH can be refined through PSH, which maintains bubbles under reduced pressure, preventing stochastic shock scattering and enhancing lesion accuracy (65). PSH lesions have demonstrated high accuracy with a 2.37-fold decrease in length and a 1.35-fold decrease in width compared to BH (45). When combined with BH, PSH can be used to target tumor margins, critical para-structural lesions, or small targets, while BH ablates the bulk of solid tumors (45).

Histotripsy may be beneficial for tumor ablation. In five rodent tumor model studies, histotripsy was shown to stimulate both local and abscopal anti-tumor immune responses (44,47,50,51,53). These immune responses are manifested by inhibiting tumor progression in both partially ablated tumors and distant, untreated tumors, and even achieving tumor regression (44,47,50,51). In the rat HCC models, it was found that at least 50% of the tumor volume had to be ablated to trigger a sufficiently effective immune response, leading to a significant reduction in the tumor burden (47,50). Additionally, histotripsy has also demonstrated synergistic effects when combined with immune checkpoint inhibition immunotherapy, even in a poor immunogenic liver cancer model (44,51). In bilateral murine Hepa1-6 HCC models, combined unilateral histotripsy and CTLA-4 blockade checkpoint inhibition achieved superior suppression of untreated tumors compared with monotherapy (51).

The immune response induced by histotripsy may primarily be driven by the mechanical destruction of cell structures, while preserving the native conformation of tumor antigens, which enhances antigen presentation by antigen-presenting cells, thereby boosting the anti-tumor immune responses (51,66). Notably, histotripsy appears to be more effective in inducing intratumoral cluster of differentiation 8-positive (CD8⁺) T cell infiltration than radiation and thermal ablation in terms of local tumor control (51). Immunogenic cell death (ICD) may be another immunologic mechanism of histotripsy. Studies of C57BL/6 mice bearing subcutaneous B16GP33 melanoma or Hepa1-6 HCC have revealed that in the course of ICD, damage-associated molecular patterns (DAMPs), including high mobility group box protein 1 (HMGB1) and calreticulin, are released after histotripsy (44,51), which facilitates the cross-presentation of tumor antigens by dendritic cells, leading to the systemic activation of CD8⁺ T cells (44,51). Further, the release of DAMPs enables cytotoxic T lymphocytes to bypass the mechanism by which tumors reduce antigen expression to suppress immune infiltration, thereby preventing tolerance to histotripsy (40). Necroptosis driven by tumor necrosis factor-α plays a key role in the early immune reaction after local ablation (51). The synergy of the combination therapy and delayed abscopal anti-tumor immune responses is linked to ferroptotic ICD driven by CD8⁺ T cells (44,51). Local and distant tumors exhibit different immune reaction mechanisms in the early stages; however, these mechanisms converge over time (44,51). Vaccination experiments in mice have confirmed the ability of histotripsy to induce ICD. Cell-free lysates generated 1 day after histotripsy conferred partial protection against subsequent B16F10 challenge tumors, whereas equivalent lysates from untreated or irradiated tumors failed to impede growth (44). These immunogenic effects require further validation in large animal models and clinical studies.

The normal wound-healing cascade is triggered after ablation, with extracellular matrix remodeling and granulation tissue formation to provide nutrition. Heo et al. (49) investigated the long-term healing response following BH treatment in rat models, and found that the liquefied tissues were absorbed within 1–2 months without leaving long-term hepatic fibrotic lesions. The residual cavities were almost completely replaced by regenerated liver parenchyma and new vessels (49,54). Similarly, swine models demonstrated rapid shrinkage of the treated areas, with the lesion volume reduced by 64% after a 4-week follow-up (11). The rapid retraction of the treated area may serve as an indicator of successful local treatment, which can be assessed through subsequent imaging.

The non-thermal and non-invasive properties of histotripsy improve the safety of the technology. While generally safe, some minor AEs were observed, most of which were transient and resolved spontaneously. The most common AEs were body wall injury and venous thrombosis. Physicians can extend the cooling intervals or reduce the time-averaged intensity of energy delivery to mitigate thermal damage caused by acoustic obstruction along the acoustic path (10,18). Another concern was local thrombus derived from cavitation damage to vascular endothelium. The proportion of portal vein branch thrombosis in the ablation area was the highest (10,11,18-20). However, studies have shown that anticoagulant therapy was generally unnecessary, even for treatment areas near hepatic veins (12,20).

Despite its advantages, several crucial factors need to be considered when using histotripsy in clinical practice. First, continuous respiratory movements can lead to an expansion of the ablation volume, particularly in the craniocaudal dimension (10,13,31,34). Researchers are exploring solutions to this challenge, such as adjusting the geometry of the ablation area, utilizing high-frequency jet ventilation, and employing robotic arm tracking (9,67-70). Second, a thick fat layer around the liver, particularly in obese patients, causes acoustic aberrations that lead to changes in location and energy intensity of the focal point (31). To address this issue, two complementary approaches have been explored. Researchers have increased the energy pulse power to compensate for tissue attenuation (59,60). They have also introduced phase delays to each array element to correct time difference in propagation, thereby reducing the required acoustic energy (31,42,48,56). Third, standard histotripsy typically relies on large transducer arrays with a high mechanical index. However, if the targeted ablation is imprecise, it will cause damage to adjacent tissues. To mitigate this, low-frequency ultrasound has been proposed due to its minimal attenuation and deeper penetration (46). When combined with bubbles, FUS can trigger strong mechanical effects that induce tissue necrosis in specific areas without causing damage to the surrounding structures (46). Fourth, the immune effects of histotripsy, particularly in combination with immunotherapy, require further validation in clinical studies. The first clinical trial showed an encouraging abscopal effect with a reduction in both untreated tumor size and carcinoembryonic antigen levels in two patients after the ablation of single tumors (35). This is a promising step toward translating preclinical findings into clinical outcomes. Finally, histotripsy requires longer treatment times than thermal ablation (52,71), with a mean treatment duration of 34±25 minutes, and a total procedure time of 221±64 minutes in clinical studies (36). To improve its efficiency, adjusting treatment parameters, including pulse frequency and treatment dose, can help optimize the procedure (63).

This study had some limitations. First, as the included studies were based on animal models, the therapeutic outcomes might not be fully applicable to human clinical trials. Second, significant heterogeneity existed across the studies in terms of the objectives, methodologies, and outcome reporting, which precluded direct data synthesis and meta-analysis. Nevertheless, our findings provide valuable preliminary insights into the potential efficacy of histotripsy and may serve as a foundation for future translational research.

Conclusions

Histotripsy is a safe therapeutic option for the local ablation of the liver, with a remarkable technical success rate of 97% in live porcine models. This method significantly reduces the risk of bleeding from hypervascularized lesions and minimizes damage to surrounding tissues. Due to its efficacy and potential immune effects, histotripsy has a distinct advantage over other local liver therapies in the treatment of liver cancer. Histotripsy has also shown promise in the fields of cell therapy and liver fibrosis treatment; however, these applications require further exploration.

Acknowledgments

None.

Footnote

Reporting Checklist: The authors have completed the PRISMA reporting checklist. Available at https://qims.amegroups.com/article/view/10.21037/qims-2025-1137/rc

Funding: This work was supported by the National Natural Science Foundation of China (No. 82171968), the Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences (CIFMS) (No. 2023-I2M-C&T-A-005), and the National High Level Hospital Clinical Research Funding (No. 2022-PUMCH-D-001).

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://qims.amegroups.com/article/view/10.21037/qims-2025-1137/coif). The authors have no conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

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