Study of microRNAs in a Decompensated Cirrhosis (EmiC)

Expression and Variance of microRNAs in a Cohort of Patients With Acute Decompensation of Cirrhosis.

Cirrhotic patients are at higher risk of sepsis due to impaired innate and adaptive immune responses. Septic complications represent a major issue in the management of cirrhotic patients, with a 1-month mortality rate of 23%, which increases to 80% at 3 months in case of associated organ failure.

Delay to treatment initiation during a septic episode may increase the risk of complications and mortality of cirrhotic patients. However, the inappropriate use of antibiotics exposes cirrhotic patients to the risk of more severe infections due to multi-resistant organisms or fungi.

The use of diagnostic markers for sepsis is limited in the context of cirrhosis because of the lack of hepatic synthesis of these markers on the one hand and non-specific inflammation related to cirrhosis on the other hand.

Therefore, it is necessary to develop new tools for the early diagnosis of sepsis and appropriate management of cirrhotic patients.

The interest of microRNAs (miRNAs) in the diagnosis and prognosis of septic shock has been reported in the general population. No studies have described circulating miRNAs or reported their interest in the diagnosis of sepsis in a population of cirrhotic patients with acute decompensation (AD).

This preliminary study of 800 circulating miRNAs will be performed in a cohort of patients with acute cirrhosis decompensation, for whom the incidence of sepsis is estimated at 40%. The aim to evaluate the interest and feasibility of a larger study on the interest of circulating miRNAs in the early diagnosis of sepsis in cirrhotic patients. The long-term objective of this study is the development of biomarkers for the early management of cirrhotic patients with sepsis and the rationalization of antibiotic use to improve their prognosis.

Study Overview

• Status: Recruiting
• Conditions: Cirrhosis; Acute Decompensation
• Intervention / Treatment: Other: blood sample at Day 0; Other: blood sample at Day 2 and Day 7; Other: stool sample at Day 0

• Study Type: Observational
• Enrollment (Estimated): 444

Contacts and Locations

• Study Contact: Name: Fanny Lebossé, PhD; Phone Number: +33 04 26 10 93 39; Email: Fanny.lebosse@chu-lyon.fr

Study Locations

• France
  • Lyon, France, 69004
    • Recruiting
    • Centre Hospitalier de la Croix Rousse
    • Contact: Fanny Lebossé, PhD; Phone Number: +33 04 26 10 93 39; Email: Fanny.lebosse@chu-lyon.fr
    • Principal Investigator: Fanny Lebossé, PhD
    • Sub-Investigator: Marielle GUILLET
    • Sub-Investigator: Céline GUICHON

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

The patients concerned are cirrhotic patients, followed in the hepatology department of Pr Zoulim, in gastroenterology department of Dr Marielle Guillet and in intensive care unit of Dr Céline Guichon (Croix Rousse Hospital, North Hospital Group, Hospices Civils de Lyon), without a history of cancer or active infection with the virus of the hepatitis B, hepatitis C virus or HIV.

2 groups will be formed:

• A group of cirrhotic patients with acute decompensation (AD group)
• A group of stable cirrhotic patients (pathological controls)

Description

Inclusion Criteria:

• Patients with cirrhosis (determined either by histopathology or by association of clinical signs of portal hypertension and hepatocellular insufficiency and radiological signs (dysmorphic liver, evidences of portal hypertension (collateral circulation, ascites)).

AND

• Not refusing his / her participation in the study after information (or non-opposition of the person of confidence if the patient has a disorder of consciousness or impaired judgment (hepatic encephalopathy) at the time of inclusion) AND

• Admitted within 48 hours for an episode of acute decompensation (acute decompensation group = AD group), which is defined by the sudden occurrence of one or more of the following clinical or biological symptoms:

  • Jaundice
  • Hepatic encephalopathy
  • oedemato-ascitic decompensation
  • Gastro-intestinal bleeding
  • Acute renal failure (according to AKIN criteria (22)) and / or hyponatremia
  • Degradation of hepatocellular functions (decrease of prothrombin time and factor V measured in blood, increase of bilirubinemia) OR
• Outpatient follow-up for stable cirrhosis, not admitted in the last 6 months for an episode of acute cirrhosis decompensation (pathological control group)

Exclusion Criteria:

• Minor or major patient under guardianship or curatorship
• Pregnant women
• Patient deprived of liberty
• History of extra-digestive cancer
• History of hepatocellular carcinoma or other hepatobiliary cancer
• Chronic infection with Hepatitis B virus (defined by the presence of Antibodies to hepatitis B core antigen (anti-HBc) and the absence of Hepatitis B surface antibodies (anti-HBs)) identified by a recent serology (less than 6 months)
• Chronic Hepatitis C Virus infection or cured for less than 6 months
• Infection with the Human Immunodeficiency Virus identified by a recent serology (less than 6 months)

Study Plan

How is the study designed?

Design Details

• Observational Models: Case-Only
• Time Perspectives: Prospective

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
acute decompensation group; patients admitted within 48 hours for acute decompensation of cirrhosis, with or without evidence of sepsis	Other: blood sample at Day 0; 40mL blood (plasma and PBMCs) will be performed at D0 (inclusion), at the time of routine exams. (20 ml will be used for study analyzes ; 20mL will constitute the biological collection); Other: blood sample at Day 2 and Day 7; 20mL blood (plasma and PBMCs) will be performed at Day 2 and Day 7 from recruitment, at the time of routine exams. These two samples will constitute the biological collection.; Other: stool sample at Day 0; stool sample (2mL) will be performed at D0 (inclusion), at the time of routine exams.
Pathological control group; patients with Chronic Liver Disease (CLD), also named stable cirrhotic patients, without any admission in the last 6 months for an acute event	Other: blood sample at Day 0; 40mL blood (plasma and PBMCs) will be performed at D0 (inclusion), at the time of routine exams. (20 ml will be used for study analyzes ; 20mL will constitute the biological collection); Other: stool sample at Day 0; stool sample (2mL) will be performed at D0 (inclusion), at the time of routine exams.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Plasma levels of 800 miRNA between the 2 subgroups of the AD group according to the retrospective diagnosis of sepsis or not	The difference of miRNAs levels will assess in patients recruited in the AD group who will be retrospectively diagnosed as septic at the time of enrollment and compare them non septic patients.	Day 0

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
miRNA profiles	Difference between miRNA profiles identified in a subgroup of patients with secondary infection during admission (DA group) and a subgroup of patients who did not developing a secondary infection on admission	Day 0
miRNA profiles	Difference between miRNA profiles identified in a subgroup of patients with secondary infection during admission (DA group) and a subgroup of patients who did not developing a secondary infection on admission	Day 2
miRNA profiles	Difference between miRNA profiles identified in a subgroup of patients with secondary infection during admission (DA group) and a subgroup of patients who did not developing a secondary infection on admission	Day 7
miRNA profiles	Difference in miRNA profiles identified in a subgroup of patients with secondary infection 6 months, 1 year and 6 years after inclusion (DA group) and a subgroup of patients developing no secondary infection during follow-up (DA group).	Day 0
miRNA profiles	Difference in miRNA profiles identified in a subgroup of patients with secondary infection 6 months, 1 year and 6 years after inclusion (DA group) and a subgroup of patients developing no secondary infection during follow-up (DA group).	Day 2
miRNA profiles	Difference in miRNA profiles identified in a subgroup of patients with secondary infection 6 months, 1 year and 6 years after inclusion (DA group) and a subgroup of patients developing no secondary infection during follow-up (DA group).	Day 7
Correlation between plasma levels of 800 miRNAs and degree of portal hypertension		Day 0
Correlation between plasma levels of 800 miRNAs and nutritional profile (Liver Frailty Index, bracchial circumference)		Day 0
miRNA profiles	Difference between miRNA profiles identified in different subgroups of patients in the DA group according to the mode progression (PREDICT study criteria)	Day 0
miRNA profiles	Difference between miRNA profiles identified in different subgroups of patients in the DA group according to the mode progression (PREDICT study criteria)	Day 2
miRNA profiles	Difference between miRNA profiles identified in different subgroups of patients in the DA group according to the mode progression (PREDICT study criteria)	Day 7
Correlation between monocyte expression of HLA-DR (mHLA-DR) and circulating miRNA expression		Day 0
Correlation between monocyte expression of HLA-DR (mHLA-DR) and circulating miRNA expression		Day 2
Difference in miRNA profiles between patients who died without liver transplantation at 6 months, 1 year and 5 years from inclusion and surviving patients.	DA group and pathological control	Day 0
Difference in miRNA profiles between patients who died without liver transplantation at 6 months, 1 year and 5 years from inclusion and surviving patients.	DA group	Day 2
Difference in miRNA profiles between patients who died without liver transplantation at 6 months, 1 year and 5 years from inclusion and surviving patients.	DA group	Day 7
Difference in miRNA profiles between patients with a new episode of cirrhosis decompensation at 6 months, 1 year and 5 years from inclusion and surviving patients (DA group)	DA group	Day 0
Difference in miRNA profiles between patients with a new episode of cirrhosis decompensation at 6 months, 1 year and 5 years from inclusion and surviving patients (DA group)	DA group	Day 2
Difference in miRNA profiles between patients with a new episode of cirrhosis decompensation at 6 months, 1 year and 5 years from inclusion and surviving patients (DA group)	DA group	Day 7
Difference between miRNA profiles / subgroup of the pathological control group presenting a 1st episode of cirrhosis decompensation and in the subgroup presenting no 1st episode of cirrhosis decompensation at 6 months, 1 and 5 years of inclusion	pathological control group	Day 0
Association between miRNA expression and PBMC phenotype in the different groups (DA and pathological controls) and subgroups	control group and DA group / Subgroups :DA group: infection or not, secondary infection or not, evolutionary profile; pathological control group: decompensation at 6 Months, 1 and 5 years or not	Day 0
Association between miRNA expression and PBMC phenotype in subgroups (DA group: infection or not, secondary infection or not, evolutionary profile at 6 Months, 1 year and 5 years or not)	DA group	Day 2
Association between miRNA expression and PBMC phenotype in subgroups (DA group: infection or not, secondary infection or not, evolutionary profile at 6 Months, 1 year and 5 years or not)	DA group	Day 7
Phenotypic and functional profiles of T and B lymphocytes from patients with cirrhosis at different stages (pathological control group and DA group)	pathological control group and DA group ; determined by spectral cytometry on the one hand, and single cell RNA sequencing and single cell secretome analysis on the other.	Day 0
Phenotypic and functional profiles of T and B lymphocytes from patients with cirrhosis at different stages (pathological control group and DA group)	DA group ; determined by spectral cytometry on the one hand, and single cell RNA sequencing and single cell secretome analysis on the other.	Day 2
Phenotypic and functional profiles of T and B lymphocytes from patients with cirrhosis at different stages (pathological control group and DA group)	DA group ; determined by spectral cytometry on the one hand, and single cell RNA sequencing and single cell secretome analysis on the other.	Day 7
Predictive value of miRNAs, ADM and cDPP3 for risk of secondary infection, further decompensation, death without liver transplantation.	control group and DA group ; Predictive value will be assessed by ROC curve ant AUC and then logistic regression will be performed.	Day 0
Predictive value of miRNAs, ADM and cDPP3 for risk of secondary infection, further decompensation, death without liver transplantation.	DA group ; Predictive value will be assessed by ROC curve ant AUC and then logistic regression will be performed.	Day 2
Predictive value of miRNAs, ADM and cDPP3 for risk of secondary infection, further decompensation, death without liver transplantation.	DA group ; Predictive value will be assessed by ROC curve ant AUC and then logistic regression will be performed.	Day 7
Correlation between i) the proportion of T and B cells circulating subpopulations and ii) circulating levels of potential biomarkers (concentrations of cytokines in plasma, concentration of circulating bacterial DNA).	control group and DA group	Day 0
Correlation between i) the proportion of T and B cells circulating subpopulations and ii) circulating levels of potential biomarkers (concentrations of cytokines in plasma, concentration of circulating bacterial DNA).	DA group	Day 2
Correlation between i) the proportion of T and B cells circulating subpopulations and ii) circulating levels of potential biomarkers (concentrations of cytokines in plasma, concentration of circulating bacterial DNA).	DA group	Day 7

Collaborators and Investigators

• Sponsor: Hospices Civils de Lyon

Study record dates

Study Major Dates

• Study Start (Actual): June 26, 2019
• Primary Completion (Estimated): December 26, 2033
• Study Completion (Estimated): June 26, 2034

Study Registration Dates

• First Submitted: April 3, 2019
• First Submitted That Met QC Criteria: April 4, 2019
• First Posted (Actual): April 5, 2019

Study Record Updates

• Last Update Posted (Actual): June 18, 2025
• Last Update Submitted That Met QC Criteria: June 17, 2025
• Last Verified: June 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Digestive System Diseases; Liver Diseases; Fibrosis; Liver Cirrhosis
• Other Study ID Numbers: 69HCL19_0020; 2019-A00266-51 (Other Identifier: ID-RCB)

Drug and device information, study documents

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