Alterations of Gut Microbiota and Serum Biochemical Markers in DILI Patients

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

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.

Study Overview

• Status: Recruiting
• Conditions: Biochemical Markers; Gut Microbiota; Drug-induced Liver Injury
• Intervention / Treatment: Other: Collect stool and blood samples from patients

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 Type: Observational
• Enrollment (Estimated): 90

Contacts and Locations

• Study Contact: Name: Huikuan Chu, M.D.; Phone Number: +8613554105386; Email: 2012xh0827@hust.edu.cn
• Study Contact Backup: Name: Wenkang Gao, Dr.; Phone Number: +8618838022896; Email: gwkmed@163.com

Study Locations

• China
  • Hubei
    • Wuhan, Hubei, China, 430022
      • Recruiting
      • Union Hospital, Tongji Medical College, Huazhong University of Science and Technology
      • Contact: Huikuan Chu, M.D.; Phone Number: +8613554105386; Email: 2012xh0827@hust.edu.cn
      • Contact: Li Zhang, Dr.; Phone Number: +8618756533130; Email: zhangli5621@163.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

• Sampling Method: Non-Probability Sample

Study Population

Patients and healthy control will be recruited mainly from the outpatient or inpatient departments of Wuhan Union Hospital.

Description

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.

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Drug-induced liver injury; history of taking hepatotoxic drugs, liver injury.	Other: Collect stool and blood samples from patients; Collect stool and blood samples from patients
Healthy control; no liver disease or other disease	Other: Collect stool and blood samples from patients; Collect stool and blood samples from patients

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
The different levels of serum aspartate transaminase/alanine transaminase (AST/ALT) in two groups	The changes will be detected by biochemical analyzers	2 years
The different levels of proinflammatory cytokines in two groups	The changes will be determined by ELISA kits	2 years
The changes of lncRNA and miRNA in two groups	The changes will be measured by quantitative polymerase chain reaction (qPCR)	2 years

Collaborators and Investigators

• Sponsor: Wuhan Union Hospital, China
• Investigators: Study Director: Huikuan Chu, M.D., Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, wuhan

Publications and helpful links

General Publications

• 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.
• 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.
• 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. doi: 10.1016/j.jhep.2018.02.024. Epub 2018 Mar 8.
• 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, Trautwein C. Intestinal Dysbiosis Amplifies Acetaminophen-Induced Acute Liver Injury. Cell Mol Gastroenterol Hepatol. 2021;11(4):909-933. doi: 10.1016/j.jcmgh.2020.11.002. Epub 2020 Nov 12.

Helpful Links

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

Study record dates

Study Major Dates

• Study Start (Actual): July 4, 2022
• Primary Completion (Estimated): July 1, 2024
• Study Completion (Estimated): December 1, 2024

Study Registration Dates

• First Submitted: July 6, 2022
• First Submitted That Met QC Criteria: July 15, 2022
• First Posted (Actual): July 20, 2022

Study Record Updates

• Last Update Posted (Actual): August 31, 2023
• Last Update Submitted That Met QC Criteria: August 28, 2023
• Last Verified: August 1, 2023

More Information

Terms related to this study

• Keywords: gut microbiota; DILI; serum biochemical markers
• Additional Relevant MeSH Terms: Chemically-Induced Disorders; Digestive System Diseases; Liver Diseases; Drug-Related Side Effects and Adverse Reactions; Poisoning; Chemical and Drug Induced Liver Injury
• Other Study ID Numbers: UHCT22354

Drug and device information, study documents

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