Introduction

Alpha-Glutathione-S-transferase (alphaGST) is a liver enzyme involved in several detoxification and antioxidant pathways 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 (MAFLD), has never been explored.
Alarmingly, the occurrence of atherosclerotic-related acute cardiovascular events (ACEs) constitutes a major cause of death in MAFLD advanced-fibrosis (AF)-affected patients.

Aims & Methods

We aimed to assess the alphaGST levels in MAFLD patients affected by different histologically-determined stages of liver fibrosis, and, by using a new-designed “Metabolic abnormalities entity- AST/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 AF, and prediction of 5-years ACEs occurrence.
We enrolled 200 MAFLD patients and a group of 30 healthy controls. All MAFLD patients received a US-guided percutaneous liver biopsy for the disease staging with the Ishak and NAFLD activity score (NAS) determination.
Anthropometrical, and clinical data, as well as a venous blood sample, were collected to assess biochemical parameters and alphaGST levels (pg/ml). Liver stiffness measurement (LSM), NAFLD fibrosis score (NFS), Fibrosis-4 (FIB-4), and BMI-AST/Platelet Ratio-Diabetes (BARD) scores, as well as the MARINA index (table 1), were determined. Naïve-ACE patients were subsequently followed up over 5 years to record ACEs occurrence ACEs were defined by:
1) Acute Myocardial Infarction (IMA),
2) Acute Coronary Syndrome (ACS),
3) Ictus cerebri (IC),
4) Transient Ischemic Attack (TIA).

Table 1. The MARINA index determination.

Results

AlphaGST levels were directly correlated with Ishak and NAS (both p<0.0001). AlphaGST levels and MARINA index were lower in F0-F2 patients compared to AF patients showing a direct linear correlation with the worsening of liver fibrosis (p<0.0001). Receiver operator characteristic (ROC) curve analysis revealed the alphaGST values of 3917 pg/ml [AUC: 0.89, p<0.0001] as the best cut-off (BCO) to identify AF, and the MARINA index threshold of 5 [AUC: 0.95, p<0.0001] as the BCO to identify AF. MARINA index expressed better predictive performance for AF identification compared to alphaGST levels alone [AUC: 0.89], NFS [AUC:0.80], FIB-4 [AUC:0.88], BARD score [AUC 0.83], and LSM [0.88]. The multinomial logistic regression revealed the MARINA index as the only variable significantly associated with the 5 years occurrence of ACEs for MAFLD patients. Moreover, MARINA [BCO > 6; AUC: 0.92, p<0.001] resulted superior to NFS [0.76], FIB-4 [0.79], BARD [AUC:0.80], and LSM [AUC: 0.80] as well as to the other quantitative variables measuring modifiable cardiovascular risk factors (blood pressure, cholesterol, triglycerides, glycosylated hemoglobin levels, and BMI) in the prediction of 5-year ACEs occurrence [HR: 2.62, p<0.0001].

Conclusion

The alphaGST dosage and the MARINA index represent novel non-invasive tools for liver fibrosis prediction and ACEs occurrence in MAFLD.

References

• Hayes PC, Bouchier IA, Beckett GJ. Glutathione S-transferase in humans in health and disease. Gut 1991; 32:813-8.
• Loguercio C, Tuccillo C, Caporaso N, et al. Determination of plasma alpha-glutathione S-transferases in patients with HCV-related chronic infection: its significance and possible clinical relevance. Liver 1998; 18:166-72.
• Eslam M, Sanyal AJ, George J. MAFLD: A Consensus-Driven Proposed Nomenclature for Metabolic Associated Fatty Liver Disease. Gastroenterology 2020; 158:1999-2014.e1.
• Castera L, Friedrich-Rust M, Loomba R. Noninvasive Assessment of Liver Disease in Patients With Nonalcoholic Fatty Liver Disease. Gastroenterology 2019;156:1264-1281.e4.
• Angelico F, Baratta F, Pastori D, et al. Assessment of hepatic fibrosis in MAFLD: A new player in the evaluation of residual cardiovascular risk? Dig Liver Dis 2021;53:383-384.

Introduction

Gastroesophageal reflux disease (GERD) is a common disorder characterized by the backward flow of stomach contents into the esophagus, impacting millions globally and significantly reducing quality of life. Typical symptoms include heartburn and acid reflux, while atypical presentations may involve noncardiac chest pain, chronic cough, and laryngitis(1).Over the past decade (2010–2021), GERD incidence and prevalence have risen sharply in Europe compared to global trends, leading to increased disability-adjusted life years (DALYs). Its multifactorial pathogenesis—driven by chemical, mechanical, psychological, and neurological mechanisms—affects symptom severity, diagnosis, and therapeutic outcomes(2).

Aims & Methods

This study aims to investigate the escalating burden of Gastroesophageal Reflux Disease (GERD) in Europe from 2010 to 2021, comparing its incidence, prevalence, and disability-adjusted life years (DALYs) with global trends to evaluate current healthcare policies and highlight the need for streamlined, evidence-based interventions that address regional disparities in disease burden. The findings will support policy refinement, ensuring healthcare systems are equipped with effective prevention strategies, optimized treatment protocols, and equitable resource allocation to reduce GERD’s long-term impact on patient health and healthcare infrastructure.
Incidence, Prevalence and disability-adjusted life years (DALYs) were calculated using the Global Burden of Disease (GBD) Database 2021. Joinpoint regression was used to calculate annual percentage changes (APCs) in ASDR, DALYs, and YLL with 95% uncertainty intervals, and significant trends over time were identified. Statistical significance was set at a p-value of <0.05

Results

Globally, GERD-related DALYs increased from 72.24 per 100,000 (95% CI: 36.45–128.77) in 2010 to 75.56 per 100,000 (95% CI: 38.05–133.87) in 2021. Prevalence rose from 9,398.70 per 100,000 (95% CI: 8,342.02–10,517.59) in 2010 to 9,838.60 per 100,000 (95% CI: 8,732.46–11,056.05) in 2021, while incidence climbed from 3,717.75 per 100,000 (95% CI: 3,298.17–4,113.24) in 2010 to 3,881.86 per 100,000 (95% CI: 3,445.56–4,299.95) in 2021.
Europe saw GERD-related DALYs rise from 75.38 per 100,000 (95% CI: 37.98–133.77) in 2010 to 77.57 per 100,000 (95% CI: 39.13–137.23) in 2021. Prevalence increased to 10,091.72 per 100,000 (95% CI: 8,938.24–11,206.79), and incidence reached 3,978.62 per 100,000 (95% CI: 3,521.81–4,418.93) in 2021.
Eastern Europe consistently showed the highest GERD burden, followed by Central Europe, while Western Europe had the lowest figures.

• Eastern Europe: 88.73 DALYs per 100,000 (95% CI: 44.67–156.85) in 2021
• Central Europe: 86.05 per 100,000 (95% CI: 43.45–152.64)
• Western Europe: 63.30 per 100,000 (95% CI: 31.76–112.67)

Conclusion

The increasing burden of Gastroesophageal Reflux Disease (GERD) in Europe from 2010 to 2021, particularly in Eastern Europe, highlights the need for targeted healthcare interventions. With rising incidence, prevalence, and disability-adjusted life years (DALYs), addressing lifestyle, environmental, and healthcare access disparities is essential. Streamlined policies, optimized treatment strategies, and preventive measures can help mitigate GERD’s impact, improve patient outcomes, and reduce the strain on healthcare systems.

References

1-Mahajan R, Kulkarni R, Stoopler ET. Gastroesophageal reflux disease and oral health: A narrative review. Spec Care Dentist. 2022;42(6):555-564. doi:10.1111/scd.12726
2-Sharma P, Yadlapati R. Pathophysiology and treatment options for gastroesophageal reflux disease: looking beyond acid. Ann N Y Acad Sci. 2021;1486(1):3-14. doi:10.1111/nyas.14501

Disclosure

No conflict of interest.