The Role of Immune Semaphorins in NAFLD

Non-Alcoholic Fatty Liver Disease Clinical Trial

— SepsisFAT  

Official title:

The Role of Immune Semaphorins in NAFLD

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04573543
• Other study ID #: UHID-05
• Status: Completed
• Start date: September 1, 2020
• Est. completion date: March 1, 2022

Study information

• Verified date: September 2020
• Source: University Hospital for Infectious Diseases, Croatia
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

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

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 160
• Est. completion date: March 1, 2022
• Est. primary completion date: September 1, 2021
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

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

Related Conditions & MeSH terms

• Biomarkers
• Fatty Liver
• Immune Response
• Liver Cirrhosis
• Liver Diseases
• Liver Fibrosis
• Non Alcoholic Steatohepatitis
• Non-Alcoholic Fatty Liver Disease

Intervention

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.
• 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.
• Measurement of serum semaphorin concentrations
Semaphorin concentration will be measured in patient sera by ELISA.
• Identification of semaphorin gene polymorphisms
Semaphorin genes will be sequenced to identify semaphorin gene polymorphisms associated with NAFLD.

Locations

Country	Name	City	State
Croatia	University Hospital for Infectious Diseases Zagreb	Zagreb

Sponsors (2)

Lead Sponsor	Collaborator
University Hospital for Infectious Diseases, Croatia	Croatian Science Foundation

Country where clinical trial is conducted

Croatia, 

References & Publications (1)

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	Identification of semaphorin gene polymorphism in patients with NAFLD	Sequencing of semaphorin genes in patients with NAFLD using Sanger sequencing	12 months
Secondary	Staging of liver steatosis	The degree of steatosis will be estimated using the controlled attenuation parameter (CAP) in patients with NAFLD	12 months
Secondary	Staging of liver fibrosis	The stage of liver fibrosis will be assessed by transient elastography (TE) in patients with NAFLD	12 months