The Efficacy of Preoperative Oral Administration of Lactobacillus Reuteri Combined With Preoperative Neoadjuvant/Conversion Immunotherapy in Patients With Primary Resectable Liver Cancer

Inclusion Criteria:

1. Understanding and voluntarily signing the informed consent form for this study;
2. Age≥18 years and ≤75 years; gender not restricted;
3. Histologically (pathologically), cytologically, or radiologically confirmed hepatocellular carcinoma (HCC);
4. Patients who require preoperative immune checkpoint inhibitor (ICI) combination therapy followed by potentially curative hepatectomy;
5. No prior systemic therapy for HCC, including chemotherapy, targeted therapy, or immunotherapy had been administered before enrollment.;
6. Patients with a history of prior curative surgery or curative ablation are allowed, except for those with recurrence within 2 years post-curative treatment or prior receipt of other local therapies;
7. At least one measurable lesion meets RECIST v1.1 criteria;
8. Child-Pugh liver function rating: grade A or B;
9. The expected survival period is greater than 3 months;
10. Patients must be able to take food orally independently;
11. Preoperative ECOG physical condition score 0-1 points;
12. Normal coagulation function, no activebleeding or thrombotic diseases; A. International standardized ratio INR≤1.5×ULN; B. Partial thromboplastin time APTT≤1.5×ULN;
13. Has adequate organ and bone marrow function, laboratory test values within 7 days prior to enrollment meet the following requirements (no blood components, cell growth factors, albumin, or other corrective drugs are allowed within 14 days prior to laboratory test), as follows: 1) Blood routine: absolute neutrophil count≥1.5×109/L; platelet count≥75×109/L; hemoglobin conten≥9.0 g/dL. 2) Liver function: serum total bilirubin≤2× upper limit of normal value (ULN); alanine aminotransferase and aspartate transferas≤5×ULN; Serum albumin ≥28 g/L; alkaline phosphatase≤5×ULN. 3) Renal function: serum creatinine≤1.5×ULN or clearance of creatinine≥50mL/min(Cockcroft-Gault formula); Urine routine results showed that urine protein \<2+; For patients with urine protein ≥2+ on routine urine tests at baseline, 24-hour urine collection and 24-hour protein quantification \<1g should be performed.

Exclusion Criteria:

1. Inability to comply with the study protocols or procedures;
2. Known intrahepatic cholangiocarcinoma, sarcomatoid hepatocellular carcinoma, mixed cell carcinoma (ICC more than 30%) and fibrolaminar cell carcinoma
3. Hepatic encephalopathy, hepatorenal syndrome, or severe decompensated cirrhosis;
4. Planned use of probiotics, yogurt, or bacterial-fortified foods during the treatment period;
5. Use of probiotics or antibiotic within 2 months before the trial;
6. Patients with severe mental illness;
7. Patients under fasting or fluid restriction (e.g., complete bowel obstruction, active gastrointestinal bleeding, etc.);
8. Patients with chronic digestive system diseases, such as irritable bowel syndrome, malabsorption syndrome, inflammatory bowel disease, or ileostomy;
9. Allergy to the trial product or its components, inability to swallow tablets, unwillingness or inability to receive intravenous administration, or a history of severe infusion-related reactions to monoclonal antibodies or any other active malignancies during the initial study treatment administration;
10. Participants in other drug, dietary supplement, probiotic, or prebiotic clinical studies within the past 1 months prior to enrollment
11. Pregnant or lactating women;
12. History of other malignancies within the past 5 years, except for completely resected basal cell carcinoma or squamous cell carcinoma of the skin, or cervical carcinoma in situ;
13. Any medical or non-medical condition that the researcher deems unsuitable for participation.