The Role of Immune Semaphorins in Steatotic Liver Disease and Sepsis

Sepsis Clinical Trial

— SepsisFAT  

Official title:

The Role of Immune Semaphorins in Steatotic Liver Disease and Sepsis

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06021743
• Other study ID #: UHID-08
• Status: Recruiting
• Start date: January 1, 2022
• Est. completion date: March 1, 2024

Study information

• Verified date: September 2023
• Source: University Hospital for Infectious Diseases, Croatia
• Contact: Nina Vrsaljko, MD
• Phone: +385914012018
• Email: nvrsaljko[@]bfm.hr
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

The impact of the complex liver immunological network on sepsis outcome is largely unknown. Steatotic liver disease (SLD) is the most common chronic liver disease with prevalence of 25% in European countries. The question remains whether patients with SLD are more prone to bacterial infections and what is the impact of persistent liver inflammation to the systemic response to infection, sepsis course and outcomes. Semaphorins are a large family of secreted and membrane-bound biological response modifiers present in many organ systems that are associated with SLD and development of fibrosis, but also might regulate systemic immune responses in sepsis. This study will investigate the association of semaphorins with sepsis outcomes in patients with SLD.

Description:

The liver, with its ability to produce acute phase proteins, complement and cytokines, plays a central role in regulating inflammation. A balanced pro- and anti-inflammatory liver response results in bacterial clearance and resolution of inflammation. Steatotic liver disease (SLD) is the most common chronic liver disease associated with systemic changes in immune response. Although there are numerous immunological links between sepsis and SLD, there is a significant gap in knowledge regarding the role of SLD in sepsis. Semaphorins were recently recognized as one of the key regulators of immune responses; while some suppress immune cells activation, proliferation and production of inflammatory cytokines, others stimulate immune responses. Semaphorins were recently shown to be associated with pathogenesis of viral hepatitis, SLD and progression of fibrosis. However, their role in sepsis is unknown. The hypothesis of this project is that semaphorins are regulators of inflammation in patients with SLD that have impact on sepsis outcome.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 160
• Est. completion date: March 1, 2024
• Est. primary completion date: February 28, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• 2 or more SIRS (Systemic Inflammatory Response Syndrome) criteria (1. Hyperthermia >38.3°C or Hypothermia <36°C; 2. Tachycardia >90 bpm; 3. Tachypnea >20 bpm; 3. Leukocytosis (>12,000 µL-1) or Leukopenia (<4,000 µL-1))
• clinical suspicion of sepsis
• enrolled within 24 hours of hospital admission

Exclusion Criteria:

• no consent
• immunosuppression
• malignancies
• immune diseases
• pregnancy
• HIV infection
• presence of chronic liver disease
• consumption of alcohol > 20 g/day

Related Conditions & MeSH terms

• Fatty Liver
• Immune Response
• Liver Diseases
• Sepsis
• Steatosis of Liver
• Toxemia

Intervention

Diagnostic Test:
• Evaluation of the degree of steatosis
The degree of steatosis will be estimated using the ultrasound and a method for grading steatosis will be measuring the degree of ultrasound attenuation by hepatic fat using a process based on simultaneous transient elastography (TE) which measures the degree of steatosis.
• Screening for the components of metabolic syndrome
Anthropometric measures including height, weight, waist circumference and hip circumference will be measured in all patients. Results of the routine laboratory tests as part of the standard diagnostic procedure will be collected: CRP, leukocyte count, ratio neutrophils and lymphocytes, hemoglobin, platelet count, urea, creatinine, bilirubin, AST, ALT, GGT, ALP, albumins, fasting glucose.
• Measurement of serum semaphorin concentrations
Semaphorin concentration will be measured in patient sera by ELISA.
• Measurement of inflammatory cytokines
A panel of pro- and anti-inflammatory markers will be determined by flow cytometer microsphere-based assay.

Locations

Country	Name	City	State
Croatia	University Hospital for Infectious Diseases Zagreb	Zagreb

Sponsors (2)

Lead Sponsor	Collaborator
University Hospital for Infectious Diseases, Croatia	Croatian Science Foundation

Country where clinical trial is conducted

Croatia, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Detection of semaphorins in patients with sepsis and SLD	Measurement of semaphorins concentration in serum of patients with SLD and sepsis by enzyme-linked immunosorbent assay (ELISA)	24 months
Primary	Impact of SLD on sepsis outcomes	Analysis of the impact of SLD and steatosis grade (grade 1 - mild steatosis, 2 - moderate, 3 - severe steatosis) on sepsis complications and outcomes.	24 months