Integration of Imaging, Molecular, Pathological, and Clinical Outcome Data in Hepatocellular Carcinoma. (IMPACT)

This prospective observational cohort will enroll adult patients with preserved liver function who undergo curative-intent resection for single BCLC 0/A HCCs.

Inclusion Criteria:

1. Able to understand the study requirements, provide written informed consent, and comply with radiological examinations, biospecimen collection, and follow-up schedules.

2. Age ≥18 years at the time of signing Informed Consent Form.

3. Newly diagnosed HCC either clinically in accordance with the version 2026 Liver Imaging Reporting and Data System (LI-RADS) or pathologically via core-needle biopsy.

4. Single BCLC 0/A HCC.

5. HCC that is amenable to R0 surgical resection with curative intent in the opinion of the multidisciplinary tumor board involved in the care of the participant.

6. No prior antitumor therapy.

7. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.

8. Child-Pugh class A liver function.

9. No contraindications to contrast-enhanced CT or MRI, such as contrast-media allergy, claustrophobia, or incompatible metallic implants.

10. No evidence of clinically significant portal hypertension (CSPH) or minor CSPH (HVPG <12 mmHg) in candidates for minor resection (fewer than 3 segments). Clinically significant portal hypertension (CSPH) can be defined either by its gold standard measurement, a hepatic venous pressure gradient (HVPG) ≥10 mmHg, or by the presence of surrogate markers such as a platelet count <100 × 109/L combined with splenomegaly.

11. Adequate major organ function, with laboratory values obtained within 7 days before enrollment meeting the following criteria:

    Hematology: absolute neutrophil count ≥ 1.0 × 10⁹/L, platelet count ≥ 75 × 10⁹/L, hemoglobin ≥ 90 g/L ((no blood transfusion, no use of granulocyte colony-stimulating factor [G-CSF], and no medication correction within 2 weeks prior to screening, except for hemoglobin).

    Blood chemistry: total bilirubin ≤1.5 × upper limit of normal (ULN); alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤5 × ULN; albumin ≥ 30 g/L (no albumin or branched-chain amino acid supplementation within 14 days prior to screening); serum creatinine (Cr) ≤1.5 × ULN or Cr clearance > 50 mL/min (Cockcroft-Gault formula); and urine protein ≤1+ ((if urine protein is ≥2+, 24-hour urine protein quantification can be performed, and patients with 24-hour urine protein quantification < 1.0 g can be enrolled).

    Coagulation: prothrombin time (PT) exceeding the normal range ≤2 s; international normalized ratio (INR) or activated partial thromboplastin time (APTT) ≤1.5 × ULN.

12. Documented virology status of hepatitis, as confirmed by screening tests for hepatitis B virus (HBV) and/or hepatitis C virus (HCV):

    Patients with hepatitis B virus (HBV) infection, such as HBsAg positive, should be tested for HBV-DNA, and HBV-DNA must be < 2000 IU/mL (< 104 copies/mL if the site has only copy/mL testing unit); for patients with HBV-DNA ≥ 2000 IU/mL, if they have received antiviral therapy (only nucleosides such as entecavir, tenofovir disoproxil fumarate, and tenofovir alafenamide fumarate tablets are allowed) for at least 1 week ,and the viral copy number is decreased more than 10-fold (1 lg) compared with that before treatment, they also can be enrolled. For patients with HBV infection, antiviral therapy is required throughout the study.

    Patients with HCV, either with resolved infection (as evidenced by detectable antibody) or chronic infection (as evidenced by detectable HCV RNA), are eligible.

    For patients with detectable HCV RNA and for whom HCV treatment is considered appropriate by the investigator, treatment should begin no sooner than 6 months following liver resection consistent with AASLD guidelines.

13. Negative HIV test at screening with the following exception: Individuals with a positive HIV test at screening are eligible if they are stable on anti-retroviral therapy, have a CD4 count ≥ 200/cells/µL, and have an undetectable viral load.

14. For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraception.

For men: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraception, and agreement to refrain from donating sperm.

Exclusion Criteria:

1. Inadequate image quality for reliable analyses (e.g., severe artifact, incomplete images).
2. Imaging evidence of tumor rupture at baseline.
3. History of hepatic encephalopathy if clinically significant within one year prior to screening.
4. Clinically symptomatic moderate-to-severe ascites.
5. History of prior malignancy.
6. Active co-infection with HBV and HCV (defined as detectable HCV RNA plus positive HBV surface antigen or HBV DNA). Patients with a history of HCV infection but who are negative for HCV RNA by Polymerase Chain Reaction (PCR) will be considered non-infected with HCV.
7. Known active co-infection with HBV and hepatitis D viral infection (HDV).
8. Active bleeding or bleeding diathesis, or those receiving ongoing thrombolytic, anticoagulant, or antiplatelet therapy.
9. High-grade esophageal or gastric fundal varices requiring intervention.
10. Inadequately controlled hypertension, defined as systolic blood pressure (BP) > 150 mmHg and/or diastolic BP > 100 mmHg (average of at least three readings at two or more sessions). Anti-hypertensive therapy to achieve these parameters is allowed.
11. History of abdominal or tracheoesophageal fistula, GI perforation, or intra-abdominal abscess within 6 months prior to screening.
12. History of intestinal obstruction and/or clinical signs or symptoms of GI obstruction, including subocclusive or occlusive syndrome related to the underlying disease, or requirement for routine parenteral hydration, parenteral nutrition, or tube feeding prior to screening.
13. Evidence of abdominal free air that is not explained by paracentesis or recent (< 3 months) abdominal surgical procedure.
14. Serious, non-healing, or dehiscing wound, active ulcer, or untreated bone fracture.
15. History of intra-abdominal inflammatory process within 6 months prior to screening, including but not limited to peptic ulcer disease, diverticulitis, or colitis.
16. Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to screening; or abdominal surgery, abdominal interventions or significant abdominal traumatic injury within 60 days prior to screening; or anticipation of need for major surgical procedure, other than potentially curative liver resection, during the study; or non-recovery from side effects of any such procedure.
17. Failuere to achieve complete healing from minor surgery (e.g., simple excision, tooth extraction) must have occurred at least 7 days before screening.
18. Chronic daily treatment with a non-steroidal anti-inflammatory drug (NSAID). The occasional use of NSAIDs for the symptomatic relief of medical conditions such as headache or fever is allowed.
19. Serious infection requiring oral or IV antibiotics and/or hospitalization within 4 weeks prior to screening, including but not limited to hospitalization for complications of infection, bacteremia, or severe pneumonia, or any active infection that, in the opinion of the investigator, could impact participant safety.
20. Pregnancy or breastfeeding, or intention of becoming pregnant during the study. Female participants of childbearing potential must have a negative serum pregnancy test result at screening.
21. Left ventricular ejection fraction (LVEF) < 50% assessed by either transthoracic echocardiogram (TTE) or multiple-gated acquisition (MUGA) scan (TTE preferred test) within 6 months prior to screening.
22. Active tuberculosis.
23. Ongoing psychotropic substance abuse that cannot be discontinued or with a clinically significant psychiatric disorder.
24. Any serious medical condition or abnormality in clinical laboratory tests that precludes an individual's safe participation in and completion of the study.
25. Subjects considered ineligible at the investigator's discretion, with the rationale explicitly documented.
26. Non R0 resection.
27. Incomplete surgical records (e.g., missing data on whether anatomical resection was performed).
28. Unable to complete scheduled postoperative surveillance.