Gut Microbiota Analysis in IAI Patients With Sepsis-associated Liver Dysfunction

NCT05628493 | Completed DMC

• 1 other identifier: 2022-11-09
• Study Type: observational
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

With the rapid development of intensive care medicine, the mortality of patients with sepsis has decreased over the past decade, but it is still the leading cause of death in intensive care unit (ICU). As an important immune and metabolic organ, the liver plays a crucial role in host defense against invading pathogens and endotoxins, as well as maintenance of metabolic and immunological homeostasis. Some studies indicate that sepsis-associated liver dysfunction (SALD) has a substantial impact on the severity and prognosis of sepsis. Intra-abdominal infections (IAI) are the second leading source of infection for sepsis after pneumonia in ICU, and are often related to high morbidity and mortality rates. Studies had found that the incidence of SALD in IAI patients was considerably higher than that of general population with sepsis. Moreover, the incidence of acute gastrointestinal injury (AGI) in IAI patients was also much higher than that in sepsis patients with other site infections, as well as the degree of AGI was more serious according to guidelines proposed by the European Society of Intensive Care Medicine (ESICM) in 2012. IAI can directly cause AGI, and a subset of patients usually progress to increased intra-abdominal pressure, which further aggravates AGI. The pathogenesis of SALD remains unclear so far, and its mechanism is complicated and elusive. Nevertheless, the unique anatomical structure of the liver make it has close association with the gut, growing evidence indicates that the gut microbiota and related metabolites are related to several liver disease. In case of sepsis, gut microbiota disorder and low microbial diversity can cause severe liver injury. An important mechanism for this phenotype is the gut-liver axis, which refers to gut microbial metabolites and nutrients are transported to the liver through the portal vein and hepatic artery to maintain the healthy metabolism of liver. Therefore, we initially conducted a retrospective study to investigate the relationship between the occurrence of AGI and SALD among IAI patients. Subsequently, a prospective study was performed to analyze and compare the diversity and composition of gut microbiota in IAI patients with or without SALD, respectively, and the dynamic changes in the gut microbiota during the first week after ICU admission were also investigated.

Conditions

Gut Microbiota; Intra-abdominal Infections; Acute Gastrointestinal Injury; Sepsis-associated Liver Dysfunction

Outcome Measures

Primary Outcomes (1)

• mortality

  28day-mortality

  Day28 after enrollment

Secondary Outcomes (2)

• Gastrointestinal function

  through study completion, an average of 7 days

• Gut microbiota

  days 1,3 and 7 after enrollment

Study Arms (2)

The non-SALD group

The patient did not meet the SALD diagnosis during the study observation period. SALD was diagnosed when the level of serum alanine aminotransferase (ALT) or aspartate aminotransferase (AST) ≥ 1000IU/L, or total bilirubin (TBIL) level \>3mg/dL during hospitalization.

Behavioral: Gut microbiota Analysis

The SALD group

The patient's maximum values of ALT, AST, or TBIL during hospitalization reached any of the SALD criteria.

Behavioral: Gut microbiota Analysis

Interventions

Gut microbiota Analysis BEHAVIORAL

fecal samples were collected per patient on days 1,3 and 7 after ICU admission. All eligible patients were given antibiotics therapy, actively control infection source by puncture drainage or surgery if necessary, as well as other supportive therapy to maintain organ function.

The SALD group; The non-SALD group

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

All patients diagnosed with intra-abdominal infection (IAI). IAI was diagnosed according to the 2005 International Sepsis Forum Consensus Conference. Briefly, the patient present with abdominal symptoms and signs, such as fever (≥38℃), tenderness, rebound pain, etc; elevated inflammatory indicators in peripheral blood and positive culture of intra-abdominal specimens.

You may qualify if:

• Adult patients (≥18 years)
• Diagnosed as Intra-abdominal infections (IAH)
• Diagnosed as sepsis 3.0

You may not qualify if:

• Discharged or died within 48 hours afterenrollment
• Known serious chronic liver disease, such as decompensated cirrhosis and end-stage liver cancer
• Hospitalization due to primary hepatobiliary disease, such as trauma, hepatitis, cholelithiasis, etc;
• Other causes of liver injury include: drugs, poisons, etc
• Pregnancy.

Sponsors & Collaborators

• Chinese Medical Association: lead

Study Sites (1)

Nanjing Drum Tower Hospital

Nanjing, Jiangsu, 210008, China

Location

Related Publications (2)

• Guo K, Ren J, Wang G, Gu G, Li G, Wu X, Chen J, Ren H, Hong Z, Wu L, Chen G, Youming D, Li J. Early Liver Dysfunction in Patients With Intra-Abdominal Infections. Medicine (Baltimore). 2015 Oct;94(42):e1782. doi: 10.1097/MD.0000000000001782.

  PMID: 26496306 RESULT

• Yang XJ, Liu D, Ren HY, Zhang XY, Zhang J, Yang XJ. Effects of sepsis and its treatment measures on intestinal flora structure in critical care patients. World J Gastroenterol. 2021 May 21;27(19):2376-2393. doi: 10.3748/wjg.v27.i19.2376.

  PMID: 34040329 RESULT

Biospecimen

Retention: SAMPLES WITH DNA

fecal samples were collected per patient on days 1,3 and 7 after ICU admission. All fecal samples were collected in sterile tubes and then stored at -80°C refrigerator. The gut microbiota analysis was performed by LC-Bio Technology Co., Ltd. (Hangzhou, China)

MeSH Terms

Conditions

Intraabdominal Infections

Condition Hierarchy (Ancestors)

Infections

Study Officials

• Wenkui Yu, Ph.D.

  Study concept and study design

  STUDY CHAIR

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: CROSS SECTIONAL
• Target Duration: 28 Days
• Sponsor Type: NETWORK
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 9, 2022
• First Posted: November 28, 2022
• Study Start: January 3, 2022
• Primary Completion: September 9, 2022
• Study Completion: September 14, 2022
• Last Updated: November 28, 2022

Record last verified: 2022-03

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)