On the basis of previous studies, this study intends to explore the efficacy of preoperative oral administration of Lactobacillus reuteri (Lr) combined with preoperative neoadjuvant/conversion therapy in patients with primary resectable hepatocellular carcinoma (HCC). We hypothesize that this combination represents a novel, microbiota-based therapeutic strategy to facilitate perioperative hepatic recovery and improve long-term survival outcomes.
This study is an open-label, randomized, blank-controlled clinical trial. Patients undergoing liver resection were randomly allocated to one of two groups. The intervention group received preoperative oral Lactobacillus reuteri (Lr) supplementation alongside neoadjuvant/conversion immunotherapy. The control group received preoperative neoadjuvant/conversion immunotherapy alone. Fecal and peripheral blood samples will be collected at baseline (pre-medication), 3 days prior to surgery, and at 5 days, 1, 3, 6, 9, 12, 18, and 24 months postoperatively. Intraoperative liver tissue samples will also be obtained. Statistical analyses will be performed to compare intergroup differences in postoperative liver function recovery, overall survival, hepatic and peripheral immune markers, and gut microbiota composition.
This study aims to develop adjuvant strategies to enhance therapeutic outcomes for HCC patients undergoing preoperative neoadjuvant/conversion immunotherapy.
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;
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;