Alpha-Glutathione-S-Transferase (AlphaGST) and MARINA Index in Metabolic-Dysfunction-Associated-Steatotic-Liver-Disease (MASLD)

NCT05804955 | Completed DMC

• 1 other identifier: 530/2016
• Study Type: observational
• Target: 260
• Locations: 1 country
• Sites: 1

Brief Summary

AlphaGST represents a liver enzyme whose serologic levels progressively increase in alcoholic and viral chronic hepatitis according to the worsening of liver fibrosis. However, its diagnostic and prognostic usefulness in Metabolic-dysfunction-Associated-Steatotic-Liver-Disease has never been explored. The investigators aimed to assess the alphaGST levels in Metabolic-dysfunction-Associated-Steatotic-Liver-Disease patients affected by different stages of liver fibrosis, and, by using a new-designed "Metabolic Abnormalities Related to lipids- Insulin resistance-AlphaGST levels" (MARINA) index, to evaluate its role as a novel non-invasive tool in the disease staging stratification, identification of the advanced fibrosis and prediction of 5-years acute cardiovascular events occurrence. The investigators enrolled 30 ehalthy controls and 200 metabolic dysfunction-associated steatotic liver disease patients (Training cohort) (TrC). As a validation cohort (VlC), between January 2018 and May 2019, 60 MASLD patients were consecutively enrolled (Validation Cohort - VlC) All Metabolic-dysfunction-Associated- Steatotic-Liver-Disease patients received an ultrasound-guided percutaneous liver biopsy for the disease staging. Liver stiffness measurement, NAFLD fibrosis score, Fibrosis-4, and body mass index-aspartate aminotransferase/Platelet Ratio-Diabetes scores as well as the MARINA index were determined. Naïve-acute cardiovascular events patients were subsequently followed up over 5 years to record acute cardiovascular events occurrence.

Conditions

Fatty Liver

Keywords

Metabolic dysfunction Associated Steatotic Liver Disease; liver fibrosis; liver cirrhosis; non-invasive biomarkers; cardiovascular risk

Outcome Measures

Primary Outcomes (2)

• Alpha-Glutathione-S-Transferase (alpha GST) prediction of advanced fibrosis

  The diagnostic accuracy of the alpha-Glutathione-S-Transferase (alphaGST) blood levels (pg/ml) in the prediction of hepatic histological-proved advanced fibrosis

  baseline

• MARINA Index prediction of advanced fibrosis

  The diagnostic accuracy of the MARINA index in the prediction of hepatic histological-proved advanced fibrosis. The MARINA index was calculated by combining the following variables: HLD \> 43.5 mg/dl (no: 1 point; yes: 2 points); HbA1c \> 5.5% (no: 1 point; yes: 2 points); AlphaGST \> 3917 pg/ml (no: 2 point; yes: 4 point). MARINA index total scores ranged from 3 to 8 points.

  baseline

Secondary Outcomes (1)

• MARINA index in the prediction of acute cardiovascular events

  five years

Study Arms (2)

Training Cohort

200 MASLD patients

Validation Cohort

60 MASLD patients

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

Study Population

After signing the informed consent, the investigators consecutively enrolled patients affected by ultrasonographic detectable bright-liver presenting the MAFLD diagnostic features:1) overweight or obesity, defined as Body Mass Index \>25 kg/m2; 2) type 2 diabetes mellitus; 3) presence of ≥ two metabolic risk abnormalities identified by (a) waist circumference ≥102 cm in men (≥ 88 cm in women), (b) blood pressure ≥ 130/85 mmHg (or specific drug treatment), (c) plasma triglycerides ≥150 mg/dL (or specific drug treatment), (d) plasma high-density-lipoprotein cholesterol \< 40 mg/dL for men (\<50 mg/dL for women) (or specific drug treatment), (e) prediabetes (fasting plasma glucose levels 100-125 mg/dL) or 2-hour post-load glucose levels 140-199 mg/dL or glycated hemoglobin 5.7%-6.4%, (f) homeostasis-model-assessment-for-insulin-resistance score ≥2.5, (g) plasma high-sensitivity C-reactive protein level \> 2 mg/L.

You may qualify if:

• age between 18 and 80 years
• MASLD diagnosis

You may not qualify if:

• presence of chronic inflammatory diseases
• acute or chronic kidney diseases
• rheumatoid arthritis, systemic lupus erythematosus, or other major systemic inflammatory diseases or tumors
• ongoing infections
• alcohol or drug abuse history
• other etiologies of chronic liver damage
• previous hepatocellular carcinoma diagnosis
• use of hepatoprotective drugs
• decompensated liver cirrhosis (Child-Pugh B and Child-Pugh C) at the moment of the enrollment or in the previous 12 months
• psychological/psychiatric problems that could have invalidated the informed consent

Sponsors & Collaborators

• University of Campania Luigi Vanvitelli: lead

Study Sites (1)

University of Campania Luigi Vanvitelli

Naples, 80138, Italy

Location

Biospecimen

Retention: SAMPLES WITH DNA

Whole blood, plasma, serum and biopsy liver samples

MeSH Terms

Conditions

Fatty Liver; Liver Cirrhosis

Condition Hierarchy (Ancestors)

Liver Diseases; Digestive System Diseases; Fibrosis; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Alessandro Federico, Professor

  University of Campania Luigi Vanvitelli

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Target Duration: 5 Years
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: March 3, 2023
• First Posted: April 7, 2023
• Study Start: January 2, 2017
• Primary Completion: June 30, 2017
• Study Completion: July 1, 2022
• Last Updated: May 16, 2024

Record last verified: 2024-05

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Time Frame: six months after the acceptance for 10 years
• Access Criteria: upon reasonable request to the corresponding author

Locations

IT (1)