Clinical trial NCT06021743: The Role of Immune Semaphorins in Steatotic Liver Disease and Sepsis
Official title: The Role of Immune Semaphorins in Steatotic Liver Disease and Sepsis
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Steatosis of Liver
Sepsis
Immune Response
Lead sponsor: University Hospital for Infectious Diseases, Croatia
Sponsor class: OTHER
Collaborators: name: Croatian Science Foundation
First posted: 2023-09-01
Enrollment: 160
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: All adult patients admitted at three clinical departments at UHID that meet inclusion criteria will be offered to participate in the study during a 24-month period.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Detection of semaphorins in patients with sepsis and SLD
timeFrame: 24 months
measure: Impact of SLD on sepsis outcomes
timeFrame: 24 months
Secondary outcomes:
Other outcomes:
Locations:
city: Zagreb
country: Croatia
facility: University Hospital for Infectious Diseases Zagreb
Study officials:
affiliation: School of Medicine, University of Zagreb
name: Neven Papic, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: