The Role of Immune Semaphorins in NAFLD (SepsisFAT)

• ClinicalTrials.gov Identifier: NCT04573543
• Recruitment Status: Recruiting
• First Posted: October 5, 2020
• Last Update Posted: October 5, 2020
• Sponsor: University Hospital for Infectious Diseases, Croatia
• Collaborator: Croatian Science Foundation
• Information provided by (Responsible Party): University Hospital for Infectious Diseases, Croatia

Study Description

Brief Summary:

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

Condition or disease	Intervention/treatment
Non-Alcoholic Fatty Liver Disease; Immune Response; Biomarkers; Liver Fibrosis; Non Alcoholic Steatohepatitis	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 Design

• Study Type: Observational
• Estimated Enrollment: 160 participants
• Observational Model: Case-Control
• Time Perspective: Prospective
• Official Title: The Role of Immune Semaphorins in NAFLD
• Actual Study Start Date: September 1, 2020
• Estimated Primary Completion Date: September 1, 2021
• Estimated Study Completion Date: March 1, 2022

Groups and Cohorts

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.

Outcome Measures

Primary Outcome Measures :

1. Detection of semaphorins in patients with NAFLD [ Time Frame: 12 months ]
   Measurement of semaphorins concentration in serum of patients with NAFLD by enzyme-linked immunosorbent assay (ELISA)
2. Identification of semaphorin gene polymorphism in patients with NAFLD [ Time Frame: 12 months ]
   Sequencing of semaphorin genes in patients with NAFLD using Sanger sequencing

Secondary Outcome Measures :

1. Staging of liver steatosis [ Time Frame: 12 months ]
   The degree of steatosis will be estimated using the controlled attenuation parameter (CAP) in patients with NAFLD
2. Staging of liver fibrosis [ Time Frame: 12 months ]
   The stage of liver fibrosis will be assessed by transient elastography (TE) in patients with NAFLD

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 70 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes
• Sampling Method: Non-Probability Sample

Study Population

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

Criteria

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

Contacts and Locations

Contacts

Contact: Branimir Gjurasin, MD; +38512826222; bgjurasin@bfm.hr

Locations

Croatia

University Hospital for Infectious Diseases Zagreb; Recruiting

Zagreb, Croatia, 10000

Contact: Neven Papic, MD, PhD +38512826222 npapic@bfm.hr

Principal Investigator: Neven Papic, MD, PhD

Sub-Investigator: Branimir Gjurasin, MD

Sub-Investigator: Anita Atelj, MD

Sub-Investigator: Juraj Krznaric, MD

Principal Investigator: Maja Mijic, MD

Sub-Investigator: Ivana Stromar Knezevic, MD, PhD

Sponsors and Collaborators

University Hospital for Infectious Diseases, Croatia

Croatian Science Foundation

Investigators

• Principal Investigator: Neven Papic, MD, PhD; University Hospital for Infectious Diseases Zagreb

More Information

• Responsible Party: University Hospital for Infectious Diseases, Croatia
• ClinicalTrials.gov Identifier: NCT04573543
• Other Study ID Numbers: UHID-05
• First Posted: October 5, 2020
• Last Update Posted: October 5, 2020
• Last Verified: September 2020

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Liver Diseases; Fatty Liver; Non-alcoholic Fatty Liver Disease; Liver Cirrhosis; Fibrosis; Pathologic Processes; Digestive System Diseases