Systemic inflammatory biomarkers in gastroesophageal reflux disease: current evidence and future perspectives

Gastroesophageal reflux disease (GERD) is a common gastrointestinal disorder that affects a large proportion of the population and is associated with impaired quality of life and increased healthcare utilization. Although GERD has traditionally been attributed to excessive reflux and dysfunction of the anti-reflux barrier, growing evidence indicates that inflammatory and immune-related processes also contribute to symptom development, mucosal injury, and disease progression. Accordingly, peripheral blood-derived inflammatory biomarkers, including the neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), lymphocyte-to-monocyte ratio (LMR), and systemic immune-inflammation index (SII), have been investigated as simple and readily available indicators of systemic inflammation. Clinical studies have suggested that these hematological indices may be associated with the presence of GERD, endoscopic phenotypes, and disease severity, although reported values and cutoff thresholds remain inconsistent. In addition, chronic low-grade inflammation, impaired epithelial barrier function, obesity-associated metabolic inflammation, and alterations in the microbiome are increasingly recognized as interacting mechanisms that may influence both local esophageal injury and systemic inflammatory responses. However, published findings remain inconsistent, and the clinical utility of these biomarkers has yet to be clearly established. This review provides an overview of the inflammatory mechanisms involved in GERD and evaluates current evidence regarding the potential role of hematological inflammatory biomarkers in clinical practice. Their strengths, current limitations, and priorities for future research are also discussed.