Clinical trial NCT03905746: Study of microRNAs in a Decompensated Cirrhosis
Official title: Expression and Variance of microRNAs in a Cohort of Patients With Acute Decompensation of Cirrhosis.
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Cirrhosis
Acute Decompensation
Lead sponsor: Hospices Civils de Lyon
Sponsor class: OTHER
First posted: 2019-04-05
Enrollment: 444
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: CASE_ONLY
Time perspective: PROSPECTIVE
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)

Brief summary: 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.


Eligibility criteria: 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)

Primary outcomes:
measure: Plasma levels of 800 miRNA between the 2 subgroups of the AD group according to the retrospective diagnosis of sepsis or not
timeFrame: Day 0
Secondary outcomes:
measure: miRNA profiles
timeFrame: Day 0
measure: miRNA profiles
timeFrame: Day 2
measure: miRNA profiles
timeFrame: Day 7
measure: miRNA profiles
timeFrame: Day 0
measure: miRNA profiles
timeFrame: Day 2
measure: miRNA profiles
timeFrame: Day 7
measure: Correlation between plasma levels of 800 miRNAs and degree of portal hypertension
timeFrame: Day 0
measure: Correlation between plasma levels of 800 miRNAs and nutritional profile (Liver Frailty Index, bracchial circumference)
timeFrame: Day 0
measure: miRNA profiles
timeFrame: Day 0
measure: miRNA profiles
timeFrame: Day 2
measure: miRNA profiles
timeFrame: Day 7
measure: Correlation between monocyte expression of HLA-DR (mHLA-DR) and circulating miRNA expression
timeFrame: Day 0
measure: Correlation between monocyte expression of HLA-DR (mHLA-DR) and circulating miRNA expression
timeFrame: Day 2
measure: Difference in miRNA profiles between patients who died without liver transplantation at 6 months, 1 year and 5 years from inclusion and surviving patients.
timeFrame: Day 0
measure: Difference in miRNA profiles between patients who died without liver transplantation at 6 months, 1 year and 5 years from inclusion and surviving patients.
timeFrame: Day 2
measure: Difference in miRNA profiles between patients who died without liver transplantation at 6 months, 1 year and 5 years from inclusion and surviving patients.
timeFrame: Day 7
measure: 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)
timeFrame: Day 0
measure: 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)
timeFrame: Day 2
measure: 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)
timeFrame: Day 7
measure: 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
timeFrame: Day 0
measure: Association between miRNA expression and PBMC phenotype in the different groups (DA and pathological controls) and subgroups
timeFrame: Day 0
measure: 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)
timeFrame: Day 2
measure: 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)
timeFrame: Day 7
measure: Phenotypic and functional profiles of T and B lymphocytes from patients with cirrhosis at different stages (pathological control group and DA group)
timeFrame: Day 0
measure: Phenotypic and functional profiles of T and B lymphocytes from patients with cirrhosis at different stages (pathological control group and DA group)
timeFrame: Day 2
measure: Phenotypic and functional profiles of T and B lymphocytes from patients with cirrhosis at different stages (pathological control group and DA group)
timeFrame: Day 7
measure: Predictive value of miRNAs, ADM and cDPP3 for risk of secondary infection, further decompensation, death without liver transplantation.
timeFrame: Day 0
measure: Predictive value of miRNAs, ADM and cDPP3 for risk of secondary infection, further decompensation, death without liver transplantation.
timeFrame: Day 2
measure: Predictive value of miRNAs, ADM and cDPP3 for risk of secondary infection, further decompensation, death without liver transplantation.
timeFrame: Day 7
measure: 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).
timeFrame: Day 0
measure: 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).
timeFrame: Day 2
measure: 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).
timeFrame: Day 7
Other outcomes:
Locations:
city: Lyon
country: France
facility: Centre Hospitalier de la Croix Rousse
Study officials:
References: