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

Inclusion criteria

• Understanding and voluntarily signing the informed consent form for this study;
• Age≥18 years and ≤75 years; gender not restricted;
• Histologically (pathologically), cytologically, or radiologically confirmed hepatocellular carcinoma (HCC);
• Patients who require preoperative immune checkpoint inhibitor (ICI) combination therapy followed by potentially curative hepatectomy;
• No prior systemic therapy for HCC, including chemotherapy, targeted therapy, or immunotherapy had been administered before enrollment.;
• 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;
• At least one measurable lesion meets RECIST v1.1 criteria;
• Child-Pugh liver function rating: grade A or B;
• The expected survival period is greater than 3 months;
• Patients must be able to take food orally independently;
• Preoperative ECOG physical condition score 0-1 points;
• Normal coagulation function, no activebleeding or thrombotic diseases; A. International standardized ratio INR≤1.5×ULN; B. Partial thromboplastin time APTT≤1.5×ULN;
• 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

• Inability to comply with the study protocols or procedures;
• Known intrahepatic cholangiocarcinoma, sarcomatoid hepatocellular carcinoma, mixed cell carcinoma (ICC more than 30%) and fibrolaminar cell carcinoma
• Hepatic encephalopathy, hepatorenal syndrome, or severe decompensated cirrhosis;
• Planned use of probiotics, yogurt, or bacterial-fortified foods during the treatment period;
• Use of probiotics or antibiotic within 2 months before the trial;
• Patients with severe mental illness;
• Patients under fasting or fluid restriction (e.g., complete bowel obstruction, active gastrointestinal bleeding, etc.);
• Patients with chronic digestive system diseases, such as irritable bowel syndrome, malabsorption syndrome, inflammatory bowel disease, or ileostomy;
• 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;
• Participants in other drug, dietary supplement, probiotic, or prebiotic clinical studies within the past 1 months prior to enrollment
• Pregnant or lactating women;
• 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;
• Any medical or non-medical condition that the researcher deems unsuitable for participation.