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

Alpha-Glutathione-S-Transferase (AlphaGST) and the MARINA Index as a Novel Predictive Biomarker and Composite Tool for Disease Impairment in the MASLD Context

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.

Study Overview

• Status: Completed
• Conditions: Fatty Liver

• Study Type: Observational
• Enrollment (Actual): 260

Contacts and Locations

Study Locations

• Italy
  • Naples, Italy, 80138
    • University of Campania Luigi Vanvitelli

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: N/A

• 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.

Description

Inclusion Criteria:

• age between 18 and 80 years
• MASLD diagnosis

Exclusion Criteria:

• 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

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort
Training Cohort; 200 MASLD patients
Validation Cohort; 60 MASLD patients

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
MARINA index in the prediction of acute cardiovascular events	The accuracy of the MARINA index in the prediction of Acute Cardiovascular Events 5 years occurrence. 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.	five years

Collaborators and Investigators

• Sponsor: University of Campania "Luigi Vanvitelli"
• Investigators: Principal Investigator: Alessandro Federico, Professor, University of Campania "Luigi Vanvitelli"

Study record dates

Study Major Dates

• Study Start (Actual): January 2, 2017
• Primary Completion (Actual): June 30, 2017
• Study Completion (Actual): July 1, 2022

Study Registration Dates

• First Submitted: March 3, 2023
• First Submitted That Met QC Criteria: March 27, 2023
• First Posted (Actual): April 7, 2023

Study Record Updates

• Last Update Posted (Actual): May 16, 2024
• Last Update Submitted That Met QC Criteria: May 13, 2024
• Last Verified: May 1, 2024

More Information

Terms related to this study

• Keywords: cardiovascular risk; liver fibrosis; liver cirrhosis; non-invasive biomarkers; Metabolic dysfunction Associated Steatotic Liver Disease
• Additional Relevant MeSH Terms: Digestive System Diseases; Liver Diseases; Fatty Liver
• Other Study ID Numbers: 530/2016

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: all individual participant data (IPD) that underlie results in a publication
• IPD Sharing Time Frame: six months after the acceptance for 10 years
• IPD Sharing Access Criteria: upon reasonable request to the corresponding author
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; CSR

Drug and device information, study documents

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