Chronic infection and metabolic stress: a converging axis driving hypertension and MASLD outcomes

Abstract

Metabolic dysfunction–associated steatotic liver disease (MASLD) is increasingly recognized as a systemic cardiometabolic disorder arising from the convergence of metabolic stress, chronic low-grade (smoldering) inflammation, and vascular pathology. MASLD extends beyond hepatic fat accumulation, and is tightly linked to arterial hypertension and cardiovascular disease, with arterial hypertension acting as a disease modifier that accelerates fibrosis progression and deteriorates long-term outcomes. Emerging evidence suggests that chronic infections, particularly Helicobacter pylori infection, may further amplify this cardiometabolic continuum by sustaining inflammatory signaling, oxidative stress, insulin resistance, and endothelial damage. These mechanisms substantially overlap with crucial pathogenic pathways implicated in MASLD progression and hypertension onset. At the molecular level, AMP-activated protein kinase (AMPK) signaling represents a key integrative axis linking energy homeostasis, inflammation, and blood pressure regulation. Pharmacological AMPK activation, exemplified by imeglimin targeting presenilin enhancer-2, highlights the translational potential of therapies addressing hepatic and vascular injury simultaneously.

This perspective summarizes clinical and mechanistic evidence supporting an integrated, systems-based framework in which chronic infection and metabolic stress converge along a shared axis to drive hypertension and MASLD. It underscores the need to incorporate metabolic regulation, cardiovascular risk modification, and selected infectious determinants into future risk stratification models and therapeutic strategies.