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

Study Overview
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Brief Summary
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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-Fatty-Liver-Disease has never been explored. The investigators aimed to assess the alphaGST levels in Metabolic-dysfunction-Associated-Fatty-Liver-Disease patients affected by different stages of liver fibrosis, and, by using a new-designed Metabolic abnormalities entity- Aspartate aminotransferase/Platelet Ratio-Inflammation-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 200 metabolic dysfunction-associated fatty liver disease patients and a group of 30 healthy controls. All Metabolic-dysfunction-Associated-Fatty-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.

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

Conditions
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Fatty Liver

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: age between 18 and 80 years MAFLD 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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Study Plan
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How is the study designed?
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What is the study measuring?
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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: (a) Metabolic alterations [plasma triglycerides >150 mg/dl or HDL < 40 mg/dl (men) and < 50 mg/dl (women): 1 point; homeostatic model assessment for insulin resistance (HOMA-IR) > 2.5 or diagnosed diabetes mellitus type 2: 1 point]; (b) Aspartateaminotransferase/Platelet Ratio (< 0.7: 1 point; > 0.7: 2 points); Inflammation (C-reactive protein < 2 mg/L: 1 point; > 2 mg/L: 2 points); Alpha-GST levels (< 3917 pg/ml: 1 point; > 3917 pg/ml: 2 points). 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: (a) Metabolic alterations [plasma triglycerides >150 mg/dl or HDL < 40 mg/dl (men) and < 50 mg/dl (women): 1 point; homeostatic model assessment for insulin resistance (HOMA-IR) > 2.5 or diagnosed diabetes mellitus type 2: 1 point]; (b) Aspartateaminotransferase/Platelet Ratio (< 0.7: 1 point; > 0.7: 2 points); Inflammation (C-reactive protein < 2 mg/L: 1 point; > 2 mg/L: 2 points); Alpha-GST levels (< 3917 pg/ml: 1 point; > 3917 pg/ml: 2 points). MARINA index total scores ranged from 3 to 8 points. | five years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Metabolic dysfunction Associated Fatty Liver Disease, liver fibrosis, liver cirrhosis, non-invasive biomarkers, cardiovascular risk