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

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], Model for End-Stage Liver Disease [MELD]), and clinical events (ascites, spontaneous bacterial peritonitis [SBP]).

In 463 adults with cirrhosis, IBI integrated interleukin-6, high-sensitivity C-reactive protein, 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 relative excess risk due to interaction/attributable proportion/synergy index; internal validation by 1,000 bootstrap resamples.

Cronbach α was 0.65; max variance inflation factors 1.58. High IBI was associated with worse CTP (odds ratio [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, whereas ascites showed an inverted-U pattern ( P -nonlinearity < 0.001) confined to CTP C; ascitic high-IBI patients showed an immunoparalysis profile (lower white blood cell count [WBC], procalcitonin, high-sensitivity C-reactive protein, albumin). IBI - sarcopenia additive interaction was supra-additive for ascites only (relative excess risk due to interaction 0.192, attributable proportion 29.7%); sarcopenia had no independent main effect.

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.