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 Type
OBSERVATIONAL
Enrollment
444
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)
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.
stool sample (2mL) will be performed at D0 (inclusion), at the time of routine exams.
Centre Hospitalier de la Croix Rousse
Lyon, France
RECRUITINGPlasma 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.
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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).
Time frame: 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).
Time frame: 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).
Time frame: Day 7
Correlation between plasma levels of 800 miRNAs and degree of portal hypertension
Time frame: Day 0
Correlation between plasma levels of 800 miRNAs and nutritional profile (Liver Frailty Index, bracchial circumference)
Time frame: 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)
Time frame: 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)
Time frame: 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)
Time frame: Day 7
Correlation between monocyte expression of HLA-DR (mHLA-DR) and circulating miRNA expression
Time frame: Day 0
Correlation between monocyte expression of HLA-DR (mHLA-DR) and circulating miRNA expression
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: Day 7
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