The Role of Immune Semaphorins in NAFLD (SepsisFAT)

To goal is to identify semaphorins that are associated with NAFLD and to investigate their relationship with variable degrees of steatosis and fibrosis.

Study Overview

• Status: Completed
• Conditions: Immune Response; Biomarkers; Liver Fibrosis; Non-Alcoholic Fatty Liver Disease; Non Alcoholic Steatohepatitis
• Intervention / Treatment: Diagnostic test: Evaluation of the degree of fibrosis and steatosis; Diagnostic test: Screening for the components of metabolic syndrome; Diagnostic test: Measurement of serum semaphorin concentrations; Diagnostic test: Identification of semaphorin gene polymorphisms

Detailed Description

Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease associated with systemic changes in immune response. 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. We have previously shown that semaphorins are associated with pathogenesis of viral hepatitis and progression of fibrosis. However, their role in NAFLD is unknown. The hypothesis of this project is that semaphorins are regulators of inflammation in patients with NAFLD. This study is designed as a prospective, non-interventional study. The main aims are: (1) to analyze serum concentration of semaphorins in patients with NAFLD; (2) to analyze tissue expression of semaphorins in patients with NAFLD; (3) to analyze semaphorin gene polymorphisms associated with NAFLD. Semaphorins could be a novel diagnostic and prognostic biomarker as well as targets for immune modulation.

• Study Type: Observational
• Enrollment (Actual): 160

Contacts and Locations

• Study Contact: Name: Branimir Gjurasin, MD; Phone Number: +38512826222; Email: bgjurasin@bfm.hr

Study Locations

• Croatia
  • Zagreb, Croatia, 10000
    • University Hospital for Infectious Diseases Zagreb

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

• Sampling Method: Non-Probability Sample

Study Population

120 patients diagnosed with NAFLD and 40 healthy controls will be included.

Description

Inclusion Criteria:

• Patients diagnosed with NAFLD according to current guidelines (AASLD, EASL)

Exclusion Criteria:

• Immunosuppression
• Malignancies
• Autoimmune diseases
• Pregnancy
• HIV
• Chronic viral hepatitis
• Presence of other chronic liver disease (hemochromatosis, Wilson's disease, toxic hepatitis, deficiency of alpha-1-antitrypsin, liver autoimmune disease)
• Consumption of alcohol > 20 g/day

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Patients with Non-alcoholic fatty liver disease; 120 patients diagnosed with NAFLD	Diagnostic test: Evaluation of the degree of fibrosis and steatosis; The degree of steatosis will be estimated using the controlled attenuation parameter (CAP), a method for grading steatosis by measuring the degree of ultrasound attenuation by hepatic fat using a process based on simultaneous transient elastography (TE) which measures the degree of fibrosis.; Diagnostic test: Screening for the components of metabolic syndrome; Anthropometric measures including body mass index (BMI), waist circumference (WC), waist hip ratio (WHR), and waist height ratio (WHtR) will be measured in all patients. Results of the routine laboratory tests as part of the standard diagnostic procedure will be collected: bilirubin, AST, ALT, GGT, ALP, albumins, WBC, neutrophil-to-lymphocyte ratio, hemoglobin, platelet count, fasting glucose, triglycerides, cholesterol, HDL and LDL. Non-invasive scores of steatosis/fibrosis will be calculated (APRI, FIB4, NAFLD score). Patients will be screened for the components of metabolic syndrome.; Diagnostic test: Measurement of serum semaphorin concentrations; Semaphorin concentration will be measured in patient sera by ELISA.; Diagnostic test: Identification of semaphorin gene polymorphisms; Semaphorin genes will be sequenced to identify semaphorin gene polymorphisms associated with NAFLD.
Controls; 40 healthy controls	Diagnostic test: Evaluation of the degree of fibrosis and steatosis; The degree of steatosis will be estimated using the controlled attenuation parameter (CAP), a method for grading steatosis by measuring the degree of ultrasound attenuation by hepatic fat using a process based on simultaneous transient elastography (TE) which measures the degree of fibrosis.; Diagnostic test: Screening for the components of metabolic syndrome; Anthropometric measures including body mass index (BMI), waist circumference (WC), waist hip ratio (WHR), and waist height ratio (WHtR) will be measured in all patients. Results of the routine laboratory tests as part of the standard diagnostic procedure will be collected: bilirubin, AST, ALT, GGT, ALP, albumins, WBC, neutrophil-to-lymphocyte ratio, hemoglobin, platelet count, fasting glucose, triglycerides, cholesterol, HDL and LDL. Non-invasive scores of steatosis/fibrosis will be calculated (APRI, FIB4, NAFLD score). Patients will be screened for the components of metabolic syndrome.; Diagnostic test: Measurement of serum semaphorin concentrations; Semaphorin concentration will be measured in patient sera by ELISA.; Diagnostic test: Identification of semaphorin gene polymorphisms; Semaphorin genes will be sequenced to identify semaphorin gene polymorphisms associated with NAFLD.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Detection of semaphorins in patients with NAFLD	Measurement of semaphorins concentration in serum of patients with NAFLD by enzyme-linked immunosorbent assay (ELISA)	12 months
Identification of semaphorin gene polymorphism in patients with NAFLD	Sequencing of semaphorin genes in patients with NAFLD using Sanger sequencing	12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Staging of liver steatosis	The degree of steatosis will be estimated using the controlled attenuation parameter (CAP) in patients with NAFLD	12 months
Staging of liver fibrosis	The stage of liver fibrosis will be assessed by transient elastography (TE) in patients with NAFLD	12 months

Collaborators and Investigators

• Sponsor: University Hospital for Infectious Diseases, Croatia
• Collaborators: Croatian Science Foundation
• Investigators: Principal Investigator: Neven Papic, MD, PhD, University Hospital for Infectious Diseases Zagreb

Publications and helpful links

General Publications

• Samadan L, Papic N, Mijic M, Knezevic Stromar I, Gasparov S, Vince A. Do Semaphorins Play a Role in Development of Fibrosis in Patients with Nonalcoholic Fatty Liver Disease? Biomedicines. 2022 Nov 23;10(12):3014. doi: 10.3390/biomedicines10123014.

Study record dates

Study Major Dates

• Study Start (Actual): September 1, 2020
• Primary Completion (Actual): September 1, 2021
• Study Completion (Actual): March 1, 2022

Study Registration Dates

• First Submitted: September 16, 2020
• First Submitted That Met QC Criteria: September 29, 2020
• First Posted (Actual): October 5, 2020

Study Record Updates

• Last Update Posted (Actual): August 30, 2023
• Last Update Submitted That Met QC Criteria: August 27, 2023
• Last Verified: September 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Fibrosis; Liver Diseases; Fatty Liver; Liver Cirrhosis; Non-alcoholic Fatty Liver Disease
• Other Study ID Numbers: UHID-05

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No