Phenotype-Specific Dose-Response Patterns of Systemic Inflammation With Hepatic Decompensation in Cirrhosis: A Cross-Sectional Study

Introduction: Systemic inflammation is associated with hepatic decompensation in cirrhosis, but whether this association follows the same dose-response pattern across different decompensation phenotypes is unknown. We examined an inflammation burden index (IBI) against severity proxies (Child-Turcotte-Pugh [CTP], MELD) and clinical events (ascites, spontaneous bacterial peritonitis [SBP]). Methods: In 463 adults with cirrhosis, IBI integrated IL-6, hs-CRP, neutrophil-to-lymphocyte ratio and procalcitonin (log1p, robust-z, equal-weight). A unified covariate set was applied; dose-response used restricted cubic splines; additive interaction with sarcopenia by RERI/AP/SI; internal validation by 1,000 bootstrap resamples. Results: Cronbach α was 0.65; max VIF 1.58. High IBI was associated with worse CTP (OR 3.50, 2.43–5.06), higher MELD (β 4.88, 3.69–6.07), ascites (OR 3.67, 2.44–5.51) and SBP (OR 2.67, 1.45–4.93; all q < 0.05); bootstrap-corrected estimates differed by <0.04 log-odds or β units. Dose-response was phenotype-specific: CTP, MELD and SBP rose monotonically, while ascites showed an inverted-U pattern (P-nonlinearity < 0.001) confined to CTP C; ascitic high-IBI patients showed an immunoparalysis profile (lower WBC, PCT, hs-CRP, albumin). IBI — sarcopenia additive interaction was supra-additive for ascites only (RERI 0.192, AP 29.7%); sarcopenia had no independent main effect. Conclusion: The IBI — decompensation association is phenotype-specific; the inverted-U for ascites likely reflects an artifact of advanced disease rather than a biological threshold. Findings are descriptive and require prospective validation.