Compositional Shift of Gut Microbiome According to the Complications in Patients With Liver Cirrhosis

Change in gut microbiome is closely associated with liver cirrhosis diseases initiation, progression, establishment, and severity. Nevertheless, compositional alterations in gut microbiome during cirrhosis development still not been evaluated, comprehensively. Here, investigators compared the gut microbial composition in cirrhosis patients to encompassing the gut microbial role in whole spectrum of disease.

Study Overview

• Status: Completed
• Conditions: Liver Cirrhosis

Detailed Description

Stool samples were collected prospectively from 240 participants (Healthy Control (HC=52) + Alcoholic Control (HC=46) + cirrhosis patients (n=142)). 16S rRNA (ribosomal ribonucleic acid) gene sequencing were performed using the MiSeq sequencer on the illumine platform and based on the phylogenetic relationship,16S-based Microbiome Taxonomic Profiling was performed to discovery gut microbial compositional shift along with cirrhosis severity progression.

• Study Type: Observational
• Enrollment (Actual): 3000

Contacts and Locations

Study Locations

• Korea, Republic of
  • Gangwondo
    • Chuncheon, Gangwondo, Korea, Republic of, 200-704
      • Department of Internal Medicine, Hallym University Chuncheon Sacred Heart Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: N/A
• Genders Eligible for Study: All

• Sampling Method: Probability Sample

Study Population

Microbiome Taxonomic Profiling was performed on 240 stool samples (Healthy Control (HC=52) + Alcoholic Control (HC=46) + cirrhosis patients (n=142)). All 142 patients were classified in six groups based on compilation: only cirrhosis, cirrhosis with hepatocellular carcinoma (HCC), cirrhosis with varices, cirrhosis with ascites, cirrhosis with 2 complications and cirrhosis with 3 or more complication.

Description

Inclusion Criteria:

1. Registered in the Hallym University Hospital
2. Presented initially sign of liver cirrhosis

3. Patients must have the following laboratory parameters at screening:

   1. Alanine aminotransferase (ALT) ≤10 × upper limit of normal (ULN)
   2. Aspartate aminotransferase (AST) ≤10 × ULN
   3. Hemoglobin ≥12 g/dL for male, ≥11 g/dL for female patients
   4. Platelets ≥ 50,000/mm3
   5. International normalized ratio (INR) ≤1.5 × ULN unless patient has known haemophilia or is stable on an anticoagulant regimen affecting INR.
   6. Albumin ≥3g/dL.
   7. Direct bilirubin ≤1.5 × ULN h) HbA1c ≤10.0%

   i) Creatinine clearance (CLcr) ≥60 mL/min, as calculated by the Cockcroft-Gault equation.

   -

   Exclusion Criteria:

   • Pregnant Female

Study Plan

How is the study designed?

Number of groups / cohorts

8

Cohorts and Interventions

Group / Cohort
Healthy Control; Total number of 52 Healthy Control Included in the study
Alcoholic Control; Total number of 46 Alcoholic Control Included in the study
Only Cirrhosis; Total 10 patients with only cirrhosis (n= 10, age 66.66±13.51 years) are included in this study
Cirrhosis+ HCC; Total 26 patients with Cirrhosis+ hepatocellular carcinoma (HCC) (n= 26, age 61.61±9.85 years) are included in this study
Cirrhosis+ Varices; Total 7 patients with Cirrhosis+ Varices (n= 7, age 48.42±15.80 years) are included in this study
Cirrhosis+ Ascites; Total number of 26 patients with Cirrhosis+ Ascites (n= 26, age 55.96±8.51years) are included in this study
Cirrhosis+ 2 Complications; Total number of 44 patients with cirrhosis with 2 complications (n=44, age 57.84±9.18 years) are included in this study
Cirrhosis+ 3 Complications; Total number of 29 patients with cirrhosis and 3 or more complication (n=29, aged 59.64±12.61 years) are included in this study

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Gut microbial compositional signature in liver cirrhosis and liver cirrhosis complications.	Gut microbial biomarkers, such as bacterial DNA and metabolic products in the feces, can provide valuable information about the gut microbiome in patients with decompensated cirrhosis, and may be useful in predicting the risk of complications and monitoring disease progression. However, more research is needed to fully understand the role of gut microbiota in decompensated cirrhosis and its complications, and to determine the utility of gut microbial biomarkers as a diagnostic or therapeutic tool in liver cirrhosis and cirrhosis with complications. Therefore, in this clinical trial the investigator will identify cirrhosis dependent bacterial species and metabolites which can have the ability to replace the invasive clinical biomarker for early detection of decompensation in cirrhosis.	2 years

Collaborators and Investigators

• Sponsor: Chuncheon Sacred Heart Hospital
• Investigators: Principal Investigator: Ki Tae Suk, PhD, Chuncheon Sacred Hallym hospital

Study record dates

Study Major Dates

• Study Start (Actual): August 15, 2018
• Primary Completion (Actual): June 15, 2021
• Study Completion (Actual): July 10, 2021

Study Registration Dates

• First Submitted: February 6, 2023
• First Submitted That Met QC Criteria: March 14, 2023
• First Posted (Actual): March 28, 2023

Study Record Updates

• Last Update Posted (Actual): March 28, 2023
• Last Update Submitted That Met QC Criteria: March 14, 2023
• Last Verified: February 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Liver Diseases; Fibrosis; Liver Cirrhosis
• Other Study ID Numbers: Liver cirrhosis, gut microbime

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No