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The Role of Immune Semaphorins in Steatotic Liver Disease and Sepsis

The Role of Immune Semaphorins in Steatotic Liver Disease and Sepsis

Status
UNKNOWN
Phases
Unknown
Study type
Observational
Source
ClinicalTrials.gov
Registry ID
NCT06021743
Acronym
SepsisFAT
Enrollment
160
Registered
2023-09-01
Start date
2022-01-01
Completion date
2024-03-01
Last updated
2023-09-07

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Immune Response, Sepsis, Steatosis of Liver

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.

Interventions

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.

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.

Semaphorin concentration will be measured in patient sera by ELISA.

DIAGNOSTIC_TESTMeasurement of inflammatory cytokines

A panel of pro- and anti-inflammatory markers will be determined by flow cytometer microsphere-based assay.

Sponsors

Croatian Science Foundation
CollaboratorOTHER_GOV
University Hospital for Infectious Diseases, Croatia
Lead SponsorOTHER

Study design

Observational model
COHORT
Time perspective
PROSPECTIVE

Eligibility

Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No

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

Design outcomes

Primary

MeasureTime frameDescription
Detection of semaphorins in patients with sepsis and SLD24 monthsMeasurement of semaphorins concentration in serum of patients with SLD and sepsis by enzyme-linked immunosorbent assay (ELISA)
Impact of SLD on sepsis outcomes24 monthsAnalysis of the impact of SLD and steatosis grade (grade 1 - mild steatosis, 2 - moderate, 3 - severe steatosis) on sepsis complications and outcomes.

Countries

Croatia

Contacts

Primary ContactNina Vrsaljko, MD
nvrsaljko@bfm.hr+385914012018

Outcome results

None listed

Source: ClinicalTrials.gov · Data processed: Feb 4, 2026