Oxidative Stress and Cirrhosis Severity: A Retrospective Cohort Analysis of Predictive and Interactive Effects with...

Oxidative stress is a central mechanism in the pathogenesis of cirrhosis, yet its clinical significance relative to established predictors remains unclear.

We conducted a retrospective cohort study of 90 patients with cirrhosis hospitalized between October 2024 and March 2025. Clinical data, biochemical parameters, systemic inflammatory indices, and oxidative stress markers [malondialdehyde (MDA), 8-epi-prostaglandin F2α (8-epi-PGF2α)] were assessed at admission. Statistical analyses included non-parametric group comparisons, Spearman correlations, logistic regression with interaction terms, ROC analysis with bootstrap confidence intervals, model calibration and discrimination metrics, reclassification indices (NRI, IDI), and decision curve analysis (DCA).

Patients with advanced encephalopathy (HE3) had significantly higher MDA levels compared with HE1 (123.4 [107.6-248.4] vs. 131.0 [66.9-301.1] ng/mL; p = 0.021), while 8-epi-PGF2α showed a non-significant but consistent trend. Both oxidative markers correlated with biochemical dysfunction (MDA with INR and albumin; 8-epi-PGF2α with direct bilirubin). ROC analyses demonstrated modest discriminative ability (AUC 0.55-0.60) compared with albumin (AUC 0.74-0.90) and INR (AUC 0.72-0.88). In regression models, albumin remained the strongest independent predictor, whereas oxidative markers did not retain significance. Interaction models suggested that oxidative stress exerted context-dependent effects, particularly in patients with elevated inflammatory indices. Incremental predictive value beyond age and albumin was minimal (ΔAUC ≤ 0.01; NRI + 2-4%). DCA confirmed no added clinical utility.

Classical clinical markers, particularly albumin and INR, dominate predictive accuracy in cirrhosis. Oxidative stress markers lack independent predictive power but consistently associate with worsening encephalopathy and liver dysfunction, underscoring their biological relevance and suggesting their role is best understood in conjunction with systemic inflammation.