Associations Between Systemic Inflammatory Markers, Metabolic Dysfunction, and Liver Fibrosis Scores in Patients with MASLD

Background: Metabolic dysfunction-associated steatotic liver disease (MASLD) has emerged as a global health challenge due to its complex pathophysiological processes. Systemic inflammation may profoundly affect disease progression, but the correlation between inflammatory markers and disease severity remains inadequately explored. This cross-sectional analysis within a prospective cohort evaluated associations of inflammatory markers (IL-6, TNF-α, hsCRP) with MASLD severity (five non-invasive scores) and metabolic indices, primarily with early-stage disease (66.7% mild fibrosis by TE). Methods: We recruited 120 patients diagnosed with MASLD. Assessment included anthropometric measurements, laboratory analyses, and non-invasive fibrosis evaluation using five validated scoring systems (APRI, FIB-4, NAFLD fibrosis score, FAST score, and transient elastography). Inflammatory markers were quantified using high-sensitivity ELISA techniques. Medication/comorbidities were recorded (statins 23.3%, diabetes drugs 26.7%), and multivariate regressions and FDR correction were applied. Results: Patients showed remarkably elevated inflammatory markers compared to reference ranges: IL-6 (15.1 ± 9.3 pg/mL), TNF-α (38.8 ± 29.1 pg/mL), and hsCRP (12.3 ± 11.1 mg/L). No correlations were found between inflammatory markers and disease severity across any non-invasive scoring system. However, TNF-α correlated significantly with waist circumference (r = 0.28, p = 0.002) and ALT (r = 0.19, p = 0.03), while showing inverse correlations with total cholesterol (r = −0.27, p = 0.03) and LDL (r = −0.22, p = 0.02). In contrast, hsCRP correlated positively with LDL (r = 0.20, p = 0.02) and WBC count (r = 0.24, p = 0.008). Conclusion: This study reveals a dissociation between systemic inflammatory markers and hepatic fibrosis severity in MASLD. Inflammatory Markers showed stronger metabolic associations than fibrosis, limiting their utility as fibrosis surrogates in early MASLD. These findings support a dual-pathway approach to MASLD management, targeting metabolic and hepatic components independently. The divergent associations of TNF-α and hsCRP with lipid profiles suggest distinct inflammatory mechanisms in MASLD.