Alterations of Gut Microbiota and Serum Biochemical Markers in DILI Patients

Recruiting

• Conditions: Drug-induced Liver Injury; Gut Microbiota; Biochemical Markers
• Interventions: Other: Collect stool and blood samples from patients

• Registration Number: NCT05465642
• Lead Sponsor: Wuhan Union Hospital, China

Brief Summary

Drug-induced liver injury is a leading cause of acute liver failure worldwide and one of the least understood areas in hepatology research. Increasing evidence has shown that drug-induced liver injury is associated with gut microbiota.

Detailed Description

Background:

Drug-induced liver injury(DILI) refers to the liver injury induced by all kinds of drugs and is the leading cause of acute liver failure worldwide. China has a large population base and a wide variety of clinical drugs, and it is common for the population to use drugs irregularly. Therefore, the incidence of DILI is increasing year by year. The pathogenesis of DILI is complicated, and there are often multiple mechanisms successively or altogether. As a result of the same effect, it is particularly important to study the pathogenesis of DILI and find its therapeutic target. Increasing evidence shows that DILI is related to the gut microbiota, which provides broader insights and opportunities for understanding and treating this disease.

Aims:

We aim to map the alterations of gut microbiota and serum biochemical markers in patients with DILI, and to investigate the effects and mechanisms of key strains on the development of DILI, providing a theoretical basis and potential targets for its treatment.

Methods:

Patients who meet the inclusion criteria will sign informed consent, their demographic data, clinical labs, serum, and feces will be collected at baseline. Fecal samples will be subject to 16S rRNA amplicon sequencing. Serum samples were taken for metabolomics detection.

Anticipated Results:

Compared to the healthy control group, patients with DILI will suffer from gut microbiota dysbiosis and have more microbes and microbial genes associated with inflammation and injury. The levels of serum biochemical markers are associated with the severity of DILI.

Implications and Future Studies:

Results of altered gut microbiome and serum biochemical markers could provide potential targets for manipulating intestinal microbiota to prevent or treat DILI.

Study Timeline

• Study Start: 2022-07-04
• Study First Submitted: 2022-07-06
• Study First Submitted QC: 2022-07-15
• Study First Posted: 2022-07-20
• Status Verified: 2023-08
• Last Update Submitted: 2023-08-28
• Last Update Posted: 2023-08-31
• Primary Completion: 2024-07
• Study Completion: 2024-12

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 90

Inclusion Criteria

1. The group of DILI:

2. aged >18 years;

3. patients who meet the diagnostic criteria of DILI in Guidelines for Diagnosis and Treatment of Drug-induced Liver Injury;

4. history of taking hepatotoxic drugs;

5. with relatively complete clinical data and good compliance.

6. The group of healthy control:

7. aged >18 years;

8. no history of liver disease and other diseases.

Exclusion Criteria

1. with hepatocellular carcinoma (HCC) or hepatic metastases;
2. combined with infectious liver diseases, such as hepatitis A virus, hepatitis B virus, hepatitis C virus, hepatitis D virus, hepatitis E virus, and human immunodeficiency virus (HIV);
3. combined with non-infectious liver diseases, such as non-alcoholic fatty liver disease, alcoholic liver disease, autoimmune liver disease, immunoglobulin G4-related liver disease, Wilson's disease, alpha 1-antitrypsin deficiency, Budd-Chiari syndrome, and other congenital liver diseases;
4. combined with severe organic lesions of other organs;
5. pregnant and lactating women.

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Healthy control	Collect stool and blood samples from patients	no liver disease or other disease
Drug-induced liver injury	Collect stool and blood samples from patients	history of taking hepatotoxic drugs, liver injury.

Primary Outcome Measures

Name	Time	Method
The changes of gut microbiota in the levels of phylum, genus, and species in two groups	2 years	The changes will be detected by genome sequencing
The different levels of serum aspartate transaminase/alanine transaminase (AST/ALT) in two groups	2 years	The changes will be detected by biochemical analyzers
The different levels of proinflammatory cytokines in two groups	2 years	The changes will be determined by ELISA kits
The changes of lncRNA and miRNA in two groups	2 years	The changes will be measured by quantitative polymerase chain reaction (qPCR)

Trial Locations

Locations (1)

Union Hospital, Tongji Medical College, Huazhong University of Science and Technology; 🇨🇳 Wuhan, Hubei, China