Microbiome Translocation in Different Circulatory Compartments in Decompensated Cirrhosis

NCT04195724 | Unknown

• 1 other identifier: 12
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 1

Brief Summary

Acquired dysfunctional immunity in cirrhosis predisposes patients to frequent bacterial infections contributing to disease progression and may lead to the development of acute-on-chronic liver failure (ACLF). Spontaneous bacterial peritonitis (SBP) is one of the most frequent infections in cirrhosis and therefore a trigger for ACLF. ACLF is characterized by systemic inflammation even in the absence of confirmed infection and associated with poor outcome. The source of ascites infection, especially in case of culture-positive SBP and bacterascites, is suspected to be bacterial translocation from gut. In decompensated cirrhosis, data on the gut microbial translocation in different circulatory compartments is limited. Moreover, the link between gut microbiome and systemic inflammation in liver disease has still not established. The transjugular intrahepatic portosystemic shunt (TIPS) is applied to treat portal hypertension which frequently leads to intestinal bleeding, life-threatening esophageal bleeding and ascites. Under the procedure of TIPS, the vein blood samples in different compartments (superior mesenteric vein, portal vein and hepatic vein) from patients with decompensated liver cirrhosis are available. Metagenomic next-generation sequencing (mNGS) is a promise approach for the diagnosis of infectious disease because a comprehensive spectrum of potential causes (viral, bacterial, fungal, and parasitic) can be identified by a single assay. Previous study reported that mNGS of cerebrospinal fluid can be applied to diagnosis of meningitis and encephalitis. Comparing to traditional bacterial culture method, mNGS method is more sensitive and rapidly in pathogen detection. Therefore, the circulating microbiome in different compartment can be characterized by means of mNGS. Here, the study aim to investigate the circulating microbiome from superior mesenteric vein (first venous outflow in gut-liver axis), hepatic vein (liver outflow), peripheral vein and ascites from patients with decompensated liver cirrhosis receiving TIPS. Before TIPS, fecal sample and unary sample are collected. And mNGS method is performed to identify the pathogen in ascites,fecal and blood samples in a single center. Ultimately, the study aim to build up the link between gut microbiome translocation and liver disease.

Conditions

Cirrhosis, Liver

Keywords

gut microbial translocation; metagenomic next-generation sequencing; transjugular intrahepatic portosystemic shunt

Outcome Measures

Primary Outcomes (1)

• The circulating microbiome in ascites,fecal and in blood of different circulatory compartments (superior mesenteric vein, peripheral vein and hepatic vein, respectively).

  mNGS and metabonomics are performed in ascites,fecal and in blood of different circulatory compartments (superior mesenteric vein, peripheral vein and hepatic vein, respectively).

  28 days

Secondary Outcomes (2)

• The improvement of gut microbiome translocation 6 months after the operation of TIPS.

  6 months after discharge

• The occurrence of decompensated events (infection, ascites, hepatic encephalopathy, gastrointestinal bleeding) 1 year after the operation of TIPS.

  1 years after discharge

Study Arms (1)

Patients with decompensated ascites and receiving TIPS

EXPERIMENTAL

Patients with decompensated ascites and receiving TIPS will be enrolled. In this study, diagnostic paracentesis will be performed to get the ascites sample before the patients receiving TIPS. Next, the blood sample from superior mesenteric vein and hepatic vein will be collected under the procedure of TIPS.

Other: mNGS for pathogen detection

Interventions

mNGS for pathogen detection OTHER

mNGS for pathogen detection and metabonomics (ascites, fecal,venous blood from superior mesenteric vein, hepatic vein and peripheral vein, respectively)

Patients with decompensated ascites and receiving TIPS

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age\>18 years old;
• Patients with decompensated liver cirrhosis;
• Patients receiving TIPS for either variceal bleeding or refractory ascites.

You may not qualify if:

• Hepatic tumor or extrahepatic related cancer;
• Not provide written consent.

Sponsors & Collaborators

• Nanfang Hospital, Southern Medical University: lead

Study Sites (1)

Nanfang Hospital

Guangzhou, Guangdong, 510515, China

RECRUITING

MeSH Terms

Conditions

Liver Cirrhosis

Condition Hierarchy (Ancestors)

Liver Diseases; Digestive System Diseases; Fibrosis; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Jinjun Chen

  Nanfang Hospital, Southern Medical University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Jinjun Chen

CONTACT

8618588531001; chjj@smu.edu.cn

Beiling Li

CONTACT

8613570541527; lbling123@163.com

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: OTHER
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Hepatology Unit, Department of Infectious Diseases

Study Record Dates

• First Submitted: December 10, 2019
• First Posted: December 12, 2019
• Study Start: November 28, 2019
• Primary Completion: December 1, 2020
• Study Completion: December 1, 2021
• Last Updated: December 13, 2019

Record last verified: 2019-12

Locations

CN (1)