Clinical trial NCT05804955: Alpha-Glutathione-S-Transferase (AlphaGST) and MARINA Index in Metabolic-Dysfunction-Associated-Steatotic-Liver-Disease (MASLD)
Official title: Alpha-Glutathione-S-Transferase (AlphaGST) and the MARINA Index as a Novel Predictive Biomarker and Composite Tool for Disease Impairment in the MASLD Context
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Fatty Liver
Keywords: Metabolic dysfunction Associated Steatotic Liver Disease
liver fibrosis
liver cirrhosis
non-invasive biomarkers
cardiovascular risk
Lead sponsor: University of Campania Luigi Vanvitelli
Sponsor class: OTHER
First posted: 2023-04-07
Enrollment: 260
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Observational model: COHORT
Time perspective: PROSPECTIVE
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.

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.


Eligibility criteria: 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

Primary outcomes:
measure: Alpha-Glutathione-S-Transferase (alpha GST) prediction of advanced fibrosis
timeFrame: baseline
measure: MARINA Index prediction of advanced fibrosis
timeFrame: baseline
Secondary outcomes:
measure: MARINA index in the prediction of acute cardiovascular events
timeFrame: five years
Other outcomes:
Locations:
city: Naples
country: Italy
facility: University of Campania Luigi Vanvitelli
Study officials:
affiliation: University of Campania Luigi Vanvitelli
name: Alessandro Federico, Professor
role: PRINCIPAL_INVESTIGATOR
References: