Systemic inflammation in metabolic dysfunction-associated steatotic liver disease: Biological relevance and diagnostic limits

Abstract

Metabolic dysfunction-associated steatotic liver disease (MASLD) is increasingly recognized as a systemic condition characterized by both hepatic and extrahepatic manifestations, in which chronic low-grade inflammation plays a key role. Insulin resistance, adipose tissue dysfunction, and lipotoxicity are among the primary drivers of this inflammatory state. These mechanisms maintain a chronic pro-inflammatory environment that promotes hepatocellular damage and fibrosis. Disruptions in the gut-liver axis also exacerbate liver inflammation, adding another dimension to the systemic nature of MASLD. Although chronic low-grade inflammation is important in MASLD, it has not translated into useful clinical biomarkers. This is largely because it is not specific to liver damage, it may also reflect other underlying metabolic conditions. Making it difficult to determine whether changes in these markers are truly due to liver fibrosis. Several blood cell-derived inflammatory markers have been proposed as accessible, low-cost tools for detecting fibrosis. However, their validation has proven difficult, as MASLD is often accompanied by metabolic comorbidities that independently trigger immune activation. In this context, Duarte et al recently published a study in World Journal of Hepatology, providing population data based on the latest cycle of the National Health and Nutrition Examination Survey and concluding that indices such as the neutrophil-to-lymphocyte ratio and the systemic inflammatory response index are associated with liver fibrosis, but show limited discriminatory accuracy compared to C-reactive protein. This editorial contextualizes these findings, analyzes why this association has not led to reliable biomarkers, and discusses how inflammation-based markers could be better integrated into existing noninvasive models.

Keywords: Metabolic dysfunction-associated steatotic liver disease; Systemic inflammation; Liver fibrosis; C-reactive protein; Biological relevance; Diagnostic limit

Core Tip: Several markers have been developed to assess systemic inflammation in metabolic dysfunction-associated steatotic liver disease, including blood cell-derived indices and C-reactive protein. Yet, a statistical association with fibrosis does not make them clinically useful. Duarte et al confirm this using National Health and Nutrition Examination Survey data. Although indices such as the neutrophil-to-lymphocyte ratio and systemic inflammatory response index are associated with fibrosis, their discriminatory power is limited. C-reactive protein performs only slightly better. This suggests that inflammatory markers should be considered contextual risk modifiers. Not standalone diagnostic tools for fibrosis detection. Future strategies should prioritize biomarkers that more directly capture fibrogenic activity.