The HistoSonics System for Treatment of Primary and Metastatic Liver Tumors Using Histotripsy (#HOPE4LIVER EU/UK)

Inclusion Criteria:

1. Subject is ≥18 years of age

2. Subject has signed the Ethics Committee (EC) or Institutional Review Board (IRB)approved trial Informed Consent Form (ICF) prior to any trial relatedtests/procedures and is willing to comply with trial procedures and requiredfollow-up assessments

3. Subject is diagnosed with hepatocellular carcinoma (HCC) or liver metastases (mets)from other primary cancers

4. Subject is able to undergo general anesthesia

5. Subject has a Child-Pugh Score of A or B (up to B8)

6. Subject has an Eastern Cooperative Oncology Group Performance Status (ECOG PS) grade 0-2 at baseline screening

7. Subject meets the following functional criteria, ≤7 days prior to theindex-procedure:

• Liver function: Alanine transaminase (ALT) and Aspartate transaminase (AST) <2.5x upper limit of normal (ULN) and bilirubin <2.5x ULN, and

• Renal function: serum creatinine <2x ULN, and

• Hematologic function: neutrophil count >1.0 x 10^9/L and platelet >50 x 10^9/L

8. Subject has an International Normalized Ratio (INR) score of <2.0 , ≤7 days prior tothe index procedure

9. Subject has not responded to and/or has relapsed and/or is intolerant of otheravailable therapies including locoregional therapies, chemotherapy, immunotherapyand targeted therapies.

10. The tumor(s) selected for histotripsy treatment must be ≤3 cm in longest diameter

11. Subject has an adequate acoustic window to visualize targeted tumor(s) usingultrasound imaging

12. Subject has a maximum of three (3) tumors to be treated with histotripsy during theindex procedure, regardless of how many tumors the subject has.

Exclusion Criteria:

1. Subject is pregnant or planning to become pregnant or nursing (lactating) during thetrial period

2. Subject is enrolled in another investigational trial and/or is takinginvestigational medication or treated with an investigational device ≤30-days priorto index procedure

3. In the Investigator's opinion, the subject has co-morbid disease(s) or condition(s)that would cause undue risk and preclude safe use of the HistoSonics System

4. Subject has a serum creatinine >2.0 mg/dL or estimated glomerular filtration rate (EGFR) <30, unless on dialysis

5. Subject has major surgical procedure or significant traumatic injury ≤2 weeks priorto the index procedure or not fully recovered from side effects/complications ofsuch procedure or trauma

6. Subject has not recovered to common terminology criteria for adverse events (CTCAE)grade 1 or better from any adverse effects (except alopecia) related to previousanti-cancer therapy

7. Subject has a history of, or suspected to have, bleeding disorders that areuncorrectable

8. Subject has a coagulopathy that is uncorrectable

9. Subject has a planned cancer treatment (e.g. resection, chemotherapy, etc.) from theindex-procedure date and prior to completion of the 30-day follow-up visit

10. Subject has previous treatment with bevacizumab that has not been discontinued >40days prior to the planned index-procedure date

11. Subject has planned bevacizumab treatment prior to completion of the 30-dayfollow-up visit

12. Subject has previous treatments with chemotherapy and/or radiotherapy that has notbeen discontinued ≥2 weeks prior to the planned index-procedure date or has notrecovered from related toxicity

13. Subject has previous treatment with immunotherapies that has not been discontinued ≥4 weeks prior to the index-procedure or has not recovered from related toxicity

14. Subject has a life expectancy less than six (<6) months

15. In the opinion of the Investigator, histotripsy is not a treatment option for thesubject

16. Subject has a concurrent condition that, in the investigator's opinion, couldjeopardize the safety of the subject or compliance with the protocol

17. Subjects' tumor(s) is not treatable by the System's working ranges (refer to UserManual)

18. Subject has a known sensitivity to contrast media and cannot be adequatelypre-medicated

19. Subjects' targeted tumor(s) has/have had prior locoregional therapy (e.g. ablation,embolization, radiation)

20. Subject is eligible for surgical resection

21. Targeted tumor(s) treatment volume overlaps a non-targeted tumor visible via imaging

22. The targeted tumor(s) is not clearly visible with diagnostic ultrasound and computedtomography (CT) or magnetic resonance (MR) imaging

23. The targeted tumor(s) is located in liver segment 1

24. The Planned Treatment Volume intended to cover the targeted tumor includes orencompasses any portion of the main portal vein, common hepatic duct, common bileduct, gallbladder or stomach/bowel