Alterations of Gut Microbiota and Serum Biochemical Markers in DILI Patients

Gut Microbiota Clinical Trial

Official title:

Alterations of Gut Microbiota and Serum Biochemical Markers in Asian Patients With Drug-induced Liver Injury

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05465642
• Other study ID #: UHCT22354
• Status: Recruiting
• Start date: July 4, 2022
• Est. completion date: December 2024

Study information

• Verified date: August 2023
• Source: Wuhan Union Hospital, China
• Contact: Huikuan Chu, M.D.
• Phone: +8613554105386
• Email: 2012xh0827[@]hust.edu.cn
• Is FDA regulated: No
• Study type: Observational [Patient Registry]

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 90
• Est. completion date: December 2024
• Est. primary completion date: July 2024
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

Inclusion Criteria:

1. The group of DILI:

1. aged >18 years;

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

3. history of taking hepatotoxic drugs;

4. with relatively complete clinical data and good compliance.

2. The group of healthy control:

1. aged >18 years;

2. 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.

Related Conditions & MeSH terms

• Biochemical Markers
• Chemical and Drug Induced Liver Injury
• Drug-induced Liver Injury
• Gut Microbiota

Intervention

Other:
• Collect stool and blood samples from patients
Collect stool and blood samples from patients

Locations

Country	Name	City	State
China	Union Hospital, Tongji Medical College, Huazhong University of Science and Technology	Wuhan	Hubei

Sponsors (1)

Lead Sponsor	Collaborator
Wuhan Union Hospital, China

Country where clinical trial is conducted

China, 

References & Publications (4)

Gong S, Lan T, Zeng L, Luo H, Yang X, Li N, Chen X, Liu Z, Li R, Win S, Liu S, Zhou H, Schnabl B, Jiang Y, Kaplowitz N, Chen P. Gut microbiota mediates diurnal variation of acetaminophen induced acute liver injury in mice. J Hepatol. 2018 Jul;69(1):51-59. — View Citation

Hartmann P, Chu H, Duan Y, Schnabl B. Gut microbiota in liver disease: too much is harmful, nothing at all is not helpful either. Am J Physiol Gastrointest Liver Physiol. 2019 May 1;316(5):G563-G573. doi: 10.1152/ajpgi.00370.2018. Epub 2019 Feb 15. — View Citation

Schneider KM, Elfers C, Ghallab A, Schneider CV, Galvez EJC, Mohs A, Gui W, Candels LS, Wirtz TH, Zuehlke S, Spiteller M, Myllys M, Roulet A, Ouzerdine A, Lelouvier B, Kilic K, Liao L, Nier A, Latz E, Bergheim I, Thaiss CA, Hengstler JG, Strowig T, Trautw — View Citation

Wu G, Win S, Than TA, Chen P, Kaplowitz N. Gut Microbiota and Liver Injury (I)-Acute Liver Injury. Adv Exp Med Biol. 2020;1238:23-37. doi: 10.1007/978-981-15-2385-4_3. — View Citation

Outcome

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

External Links

•   This web provides information of Human Subjects Protection in this study