Interleukin-38: A Candidate Biomarker for Disease Severity in Advanced Steatotic Liver Disease

Interleukin-38 (IL-38) is an anti-inflammatory IL-1-family cytokine implicated in limiting tissue injury by its anti-inflammatory character. We evaluated the diagnostic discrimination and prognostic relevance in steatotic liver disease (SLD).

We conducted a prospective, monocentric cohort analysis of 184 patients with SLD (n = 176) and healthy controls (n = 8). We tested group differences using Mann-Whitney U or Kruskal-Wallis; determined diagnostic quality using ROC curves. Logistic regression was used to assess the relationship with decompensation. Associations with MELD and routine laboratory parameters were modeled using Spearman correlation and linear regression. We analyzed survival using Kaplan-Meier and Cox regression.

IL-38 concentrations were found to be higher in decompensated (n = 94) than in compensated patients (n = 82) (p < 0.001). MELD was positively associated with IL-38 (p < 0.001; 95% CI 0.057-0.120). This corresponds to a 9.2% increase in IL-38 per 1-point increase in MELD (95% CI 5.9-12.7%). IL-38 correlated positively with the MELD score (p < 0.001) and with bilirubin/AST/LDH. In the combination model (MELD + IL-38 ± CRP), a very good AUC ≈ 0.92 was achieved.

IL-38 reflects the severity of steatotic liver disease and is therefore a potentially predictive biomarker for early risk stratification and therapy monitoring.