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The Role of Immune Semaphorins in Steatotic Liver Disease and Sepsis

Recruiting
Conditions
Steatosis of Liver
Sepsis
Immune Response
Interventions
Diagnostic Test: Evaluation of the degree of steatosis
Diagnostic Test: Screening for the components of metabolic syndrome
Diagnostic Test: Measurement of serum semaphorin concentrations
Diagnostic Test: Measurement of inflammatory cytokines
Registration Number
NCT06021743
Lead Sponsor
University Hospital for Infectious Diseases, Croatia
Brief 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.

Detailed 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 & Eligibility

Status
RECRUITING
Sex
All
Target Recruitment
160
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

Study & Design

Study Type
OBSERVATIONAL
Study Design
Not specified
Arm && Interventions
GroupInterventionDescription
SepsisEvaluation of the degree of steatosisPatients hospitalized due to the sepsis
SepsisMeasurement of serum semaphorin concentrationsPatients hospitalized due to the sepsis
SepsisMeasurement of inflammatory cytokinesPatients hospitalized due to the sepsis
SepsisScreening for the components of metabolic syndromePatients hospitalized due to the sepsis
Primary Outcome Measures
NameTimeMethod
Impact of SLD on sepsis outcomes24 months

Analysis of the impact of SLD and steatosis grade (grade 1 - mild steatosis, 2 - moderate, 3 - severe steatosis) on sepsis complications and outcomes.

Detection of semaphorins in patients with sepsis and SLD24 months

Measurement of semaphorins concentration in serum of patients with SLD and sepsis by enzyme-linked immunosorbent assay (ELISA)

Secondary Outcome Measures
NameTimeMethod

Trial Locations

Locations (1)

University Hospital for Infectious Diseases Zagreb

🇭🇷

Zagreb, Croatia

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