Clinical Study on BIFICO Accelerating Postoperative Liver Function Recovery in Patients With Hepatocellular Carcinoma

Study Overview
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Brief Summary
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On the basis of previous studies, this study intends to explore the effect of BIFICO on liver function recovery of patients with hepatocellular carcinoma (HCC) after surgery, so as to provide a new method for accelerating liver function recovery of HCC patients during perioperative period. This project is an open, randomized, blank-controlled clinical study. Liver resection patients were randomly divided into two groups, one group received continuous administration of BIFICO during perioperative period, and the dosage was controlled according to the instructions. The other group was a blank control. Stool samples were collected at three time points (before medication, before and after surgery) in two groups. Statistical analysis was performed to compare the differences of postoperative liver function and preoperative and postoperative gut microbiota between the two groups. Through this study, the investigators aimed to verify the beneficial changes of intestinal microflora in HCC patients with BIFICO during perioperative period .

Detailed Description
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Hepatocellular carcinoma (HCC) is one of the most common malignant tumors in the digestive system, with a high incidence in the world and the third highest mortality rate among all malignant tumors in China. In recent years, studies have found that intestinal microflora disorder can also promote the occurrence and development of HCC through various ways, such as endotoxemia, metabolic disorders, and increased risk of exposure to HBV and aflatoxin. In the treatment of HCC, in addition to the traditional comprehensive treatment based on surgical resection, the treatment for intestinal microflora disorder also plays a unique role in improving prognosis and alleviating complications. At present, increasing the number of beneficial bacteria through probiotics is an important method to restore the ecological balance of intestinal microorganisms. Probiotics can maintain the balance of intestinal microecology and the integrity of intestinal mucosal barrier by inhibiting the growth of harmful bacteria, stimulating fermentation, stimulating the proliferation of intestinal mucosal cells and activating the immune system. The preliminary study of this project has shown that the difference of intestinal flora in patients with HCC has a certain impact on the recovery speed of liver function after hepatectomy, and the core flora affecting postoperative liver function is bifidobacteria. Meanwhile, animal experiments have also verified that bifidobacteria can improve the postoperative liver function of mice. Therefore, improving the structure and environment of intestinal microorganisms, increasing the colonization of beneficial bacteria and enhancing the diversity of bacteria are very important to accelerate the recovery of liver function after hepatectomy for patients with HCC. In this project, it is planned to use bifidobacteria-rich BIFICO as an intervention drug to sustained medication in the perioperative period of hepatectomy patients with HCC, and observe the recovery of postoperative liver function.

Official Title
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Clinical Study on BIFICO Accelerating Postoperative Liver Function Recovery in Patients With Hepatocellular Carcinoma

Conditions
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Gut Microbiota, Hepatocellular Carcinoma, Bifidobacterium

Intervention / Treatment
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* Drug: BIFICO


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age between 18 to 80 years old Imaging diagnosis of primary HCC, without other malignancies No antibiotic treatment within two weeks before surgery Regular diet and no severe diarrhea Laparoscopic or open hepatectomy is performed Exclusion Criteria: No liver resection is performed No preoperative or postoperative stool samples during the perioperative period Pathological diagnosis is not HCC

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Bifico Group<br>Continued administration during perioperative period | Drug: BIFICO<br>* Live combined Bifidobacterium, Lactobacillus and Enterococcus Capsules<br>|
| No Intervention: Control Group<br>No intervention | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Comparison of liver function recovery with total bilirubin and prothrombin activity | The liver function recovery of the two groups on the fifth day after surgery was compared, and t-test was used to verify whether there was a significant difference between the two groups. Total bilirubin and prothrombin activity were used to assess liver function. | Five days after the surgery | 
| The alpha and beta diversity analysis of gut microbiota | We will use 16S rRNA sequencing to measure fecal sample. The alpha and beta diversity of gut microbiota between two groups will be analyzed, including a series of statistical analysis indexes such as Chao, Shannon, Simpsonace, Simpson and Coverage, in order to reflect the microbial community diversity. | Baseline (Before the surgery) | 
| The alpha and beta diversity analysis of gut microbiota | We will use 16S rRNA sequencing to measure fecal sample. The alpha and beta diversity of gut microbiota between two groups will be analyzed, including a series of statistical analysis indexes such as Chao, Shannon, Simpsonace, Simpson and Coverage, in order to reflect the microbial community diversity. | Five days after the surgery | 
| Species composition and differential analysis of gut microbiota | We will use 16S rRNA sequencing to measure fecal sample. Based on the results of species annotation, the community histogram, the community heatmap and the Wayne map will be used to analyze the species composition of the sample; the PCA、PCoA and NMDS analysis will be used to assess the similarities and differences in species composition between the two groups. To further screen the species with significant differences, the LEfSe difference discriminant analysis will be used. | Baseline (Before the surgery) | 
| Species composition and differential analysis of gut microbiota | We will use 16S rRNA sequencing to measure fecal sample. Based on the results of species annotation, the community histogram, the community heatmap and the Wayne map will be used to analyze the species composition of the sample; the PCA、PCoA and NMDS analysis will be used to assess the similarities and differences in species composition between the two groups. To further screen the species with significant differences, the LEfSe difference discriminant analysis will be used. | Five days after the surgery |