NCT06021743

The Role of Immune Semaphorins in Steatotic Liver Disease and Sepsis

• Status: Unknown
• Phase: —
• Study type: Observational
• Enrollment: 160 (estimated)
• Sponsor: University Hospital for Infectious Diseases, Croatia · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

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.

Conditions

• Steatosis of Liver
• Sepsis
• Immune Response

Interventions

Type	Name	Description
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.
DIAGNOSTIC_TEST	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.
DIAGNOSTIC_TEST	Measurement of serum semaphorin concentrations	Semaphorin concentration will be measured in patient sera by ELISA.
DIAGNOSTIC_TEST	Measurement of inflammatory cytokines	A panel of pro- and anti-inflammatory markers will be determined by flow cytometer microsphere-based assay.

Timeline

• Start date: 2022-01-01
• Primary completion: 2024-02-28
• Completion: 2024-03-01
• First posted: 2023-09-01
• Last updated: 2023-09-07

Locations

1 site across 1 country: Croatia