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Microbiome/Peptidome-based Model for Non-invasive Detection of High-risk Gastroesophageal Varices in Compensated Cirrhosis (CHESS1901/APPHA1901)

Conditions
Compensated Cirrhosis
Interventions
Diagnostic Test: esophagogastroduodenoscopy
Registration Number
NCT03990753
Lead Sponsor
Nanfang Hospital, Southern Medical University
Brief Summary

Variceal hemorrhage is a lethal complication in patients with cirrhosis and portal hypertension. Identification of varices needing treatment in compensated cirrhosis is, therefore, of great therapeutic and prognostic importance. The gold standard for diagnosing gastroesophageal varices and evaluating the risk of variceal hemorrhage is esophagogastroduodenoscopy. According to the Baveno VI consensus, for those with high-risk varices (HRV), either non-selective beta blockers or endoscopic band ligation is recommended for the prevention of the first variceal bleeding. However, the invasiveness and uncomfortableness during the esophagogastroduodenoscopy procedure has hindered its use in clinical practice, especially in patients with compensated cirrhosis. Sufficient accurate non-invasive tools for detection of HRV are warranted to safely avoid the use of esophagogastroduodenoscopy.

Advanced technologies including next-generation sequencing and MALDI-TOF mass spectrometry have the potential to be applied in this field. The latter is a widespread adopted tool in clinical microbiology for rapid, accurate and cost-effective identification of cultured bacteria and fungi. Recently, microbiome and peptidome have been proved their roles in the end-stage liver disease (e.g. cirrhosis, hepatocellular carcinoma), which may exhibit predictive capacity of HRV. In the present study, the investigators aim to conduct a prospective, multicenter diagnostic trial in 12 sites in China, 1 site in Turkey and 1 site in Thailand to evaluate the diagnostic performance of the microbiome/peptidome-based model for HRV detection in compensated cirrhosis.

Detailed Description

Variceal hemorrhage is a lethal complication in patients with cirrhosis and portal hypertension. Identification of varices needing treatment in compensated cirrhosis is, therefore, of great therapeutic and prognostic importance. The gold standard for diagnosing gastroesophageal varices and evaluating the risk of variceal hemorrhage is esophagogastroduodenoscopy. According to the Baveno VI consensus, for those with high-risk varices (HRV), either non-selective beta blockers or endoscopic band ligation is recommended for the prevention of the first variceal bleeding. However, the invasiveness and uncomfortableness during the esophagogastroduodenoscopy procedure has hindered its use in clinical practice, especially in patients with compensated cirrhosis. Sufficient accurate non-invasive tools for detection of HRV are warranted to safely avoid the use of esophagogastroduodenoscopy.

Advanced technologies including next-generation sequencing and MALDI-TOF mass spectrometry have the potential to be applied in this field. The latter is a widespread adopted tool in clinical microbiology for rapid, accurate and cost-effective identification of cultured bacteria and fungi. Recently, microbiome and peptidome have been proved their roles in the end-stage liver disease (e.g. cirrhosis, hepatocellular carcinoma), which may exhibit predictive capacity of HRV. In the present study, the investigators aim to conduct a prospective, multicenter diagnostic trial in 12 sites (The First Hospital of Lanzhou University; Zhujiang Hospital of Southern Medical University; Nanfang Hospital of Southern Medical University; Xingtai People's Hospital; Zhongda Hospital, Medical School, Southeast University; The Third People's Hospital affiliated to Jiangsu University; Guangdong Second Provincial General Hospital; Tianjin Infectious Disease Hospital; Lishui Municipal Central Hospital; The Second Hospital of Anhui Medical University; Xi'an Gaoxin Hospital; The Sixth People's Hospital of Shenyang) in China, 1 site (Ankara University School of Medicine) in Turkey and 1 site (King Chulalongkorn Memorial Hospital affiliated to Chulalongkorn University) in Thailand to evaluate the diagnostic performance of the microbiome/peptidome-based model for HRV detection in compensated cirrhosis.

Recruitment & Eligibility

Status
UNKNOWN
Sex
All
Target Recruitment
1000
Inclusion Criteria
  • age 18-75 years;
  • confirmed compensated cirrhosis based on liver biopsy or clinical findings;
  • without decompensated events (e.g. ascites, bleeding, or overt encephalopathy);
  • scheduled to undergo esophagogastroduodenoscopy;
  • estimated survival time> 24 months, and model for end-stage liver disease (MELD) score< 19, and without liver transplant;
  • with written informed consent.
Exclusion Criteria
  • contradictions for esophagogastroduodenoscopy;
  • use of antibiotics, prebiotics, probiotics and proton pump inhibitors within 3 months upon recruitment.
  • pregnancy or unknown pregnancy status.

Study & Design

Study Type
OBSERVATIONAL
Study Design
Not specified
Arm && Interventions
GroupInterventionDescription
Overall eligible participantsesophagogastroduodenoscopyEligible participants will receive standard esophagogastroduodenoscopy and microbiome/peptidome examination.
Primary Outcome Measures
NameTimeMethod
Diagnostic performance of microbiome/peptidome-based model for high-risk varices1 day

Diagnostic performance of microbiome/peptidome-based model to determine the presence or absence of high-risk varices when compared with esophagogastroduodenoscopy as the reference standard

Secondary Outcome Measures
NameTimeMethod
Diagnostic performance of microbiome/peptidome-based model for decompensation or death3 years

Diagnostic performance of microbiome/peptidome-based model to determine the presence or absence of decompensation (defined as development of ascites, bleeding, or overt encephalopathy) or death within 3-year follow-up

Diagnostic performance of microbiome/peptidome-based model for hepatic venous pressure gradient1 day

Diagnostic performance of microbiome/peptidome-based model to determine the level of hepatic venous pressure gradient

Trial Locations

Locations (14)

The Second Affiliated Hospital of Anhui Medical University

🇨🇳

Hefei, Anhui, China

The First Hospital of Lanzhou University

🇨🇳

Lanzhou, Gansu, China

Guangdong Second Provincial General Hospital

🇨🇳

Guangzhou, Guangdong, China

Nanfang Hospital of Southern Medical University

🇨🇳

Guangzhou, Guangdong, China

Zhujiang Hospital of Southern Medical University

🇨🇳

Guangzhou, Guangdong, China

The Third Hospital of Zhenjiang Affiliated Jiangsu University

🇨🇳

Zhenjiang, Jiangsu, China

Zhongda Hospital, Medical School, Southeast University

🇨🇳

Nanjing, Jiangsu, China

Xingtai People's Hospital

🇨🇳

Xingtai, Hebei, China

Xi'an Gaoxin Hospital

🇨🇳

Xi'an, Shanxi, China

Tianjin Second People's Hospital

🇨🇳

Tianjin, Tianjin, China

The Sixth People's Hospital of Shenyang

🇨🇳

Shenyang, Liaoning, China

Zhejiang University Lishui Hospital

🇨🇳

Lishui, Zhejiang, China

King Chulalongkorn Memorial Hospital affiliated to Chulalongkorn University

🇹🇭

Bangkok, Thailand

Ankara University School of Medicine

🇹🇷

Ankara, Turkey

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