Study of microRNAs in a Decompensated Cirrhosis

NCT03905746 | Recruiting

• 2 other identifiers: 69HCL19_00202019-A00266-51
• Study Type: observational
• Target: 444
• Locations: 1 country
• Sites: 1

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.

Conditions

Cirrhosis; Acute Decompensation

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (32)

• miRNA profiles

  Day 0

• miRNA profiles

  Day 2

• miRNA profiles

  Day 7

• miRNA profiles

  Day 0

• miRNA profiles

  Day 2

Study Arms (2)

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; Other: blood sample at Day 2 and Day 7; Other: stool sample at Day 0

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; Other: stool sample at Day 0

Interventions

blood sample at Day 0 OTHER

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)

Pathological control group; acute decompensation group

blood sample at Day 2 and Day 7 OTHER

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.

acute decompensation group

stool sample at Day 0 OTHER

stool sample (2mL) will be performed at D0 (inclusion), at the time of routine exams.

Pathological control group; acute decompensation group

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• 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)

You may qualify if:

• 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
• 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)

You may not qualify if:

• 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)

Sponsors & Collaborators

• Hospices Civils de Lyon: lead

Study Sites (1)

Centre Hospitalier de la Croix Rousse

Lyon, 69004, France

RECRUITING

Biospecimen

Retention: SAMPLES WITH DNA

Plasma and peripheral blood mononuclear cells (PBMCs) will be collected at D0, D2 and D7 from enrolment.

MeSH Terms

Conditions

Fibrosis

Condition Hierarchy (Ancestors)

Pathologic Processes; Pathological Conditions, Signs and Symptoms

Central Study Contacts

Fanny Lebossé, PhD

CONTACT

04 26 10 93 39; Fanny.lebosse@chu-lyon.fr

Study Design

• Study Type: observational
• Observational Model: CASE ONLY
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 3, 2019
• First Posted: April 5, 2019
• Study Start: June 26, 2019
• Primary Completion (Estimated): December 26, 2033
• Study Completion (Estimated): June 26, 2034
• Last Updated: June 18, 2025

Record last verified: 2025-06

Locations

FR (1)