PROGRESSIVE SYSTEMIC INFLAMMATION PRECEDES DECOMPENSATION IN COMPENSATED CIRRHOSIS

Abstract

Background & AimsSystemic inflammation is a driver of decompensation in cirrhosis with unclear relevance in the compensated stage. We evaluated inflammation and bacterial translocation markers in compensated cirrhosis and their dynamics in relation to the first decompensation. MethodsThis study is nested within the PREDESCI trial, which investigated non-selective beta-blockers for preventing decompensation in compensated cirrhosis and clinically significant portal hypertension (CSPH; HVPG≥10mmHg). Blood biomarkers were measured at baseline and at 1 and 2 years in patients who remained compensated and had available samples (n=164). Values of patients with CSPH were split at each time point by decompensation development in the next time interval after sampling. We also included 54 patients with cirrhosis and subclinical portal hypertension (PH) and 35 controls. We assessed inflammation markers (interleukin-6 [IL-6], tumor necrosis factor-alpha, von Willebrand factor [vWF], C-reactive protein), macrophage activation (CD14, CD163), intestinal barrier integrity (fatty acid-binding protein [FABP], haptoglobin), and bacterial translocation (lipopolysaccharide [LPS]). ResultsIL-6, CD163, and vWF were higher (p<0.01) at baseline in patients with cirrhosis and CSPH compared to those with subclinical PH and controls. IL-6 increased (p<0.05) at 1-year in CSPH patients, with a greater rise in those who developed decompensation. CD163 was higher (p<0.01) in patients who decompensated at baseline and 1- and 2-year. FABP was elevated (p<0.01) in CSPH patients compared to subclinical PH and controls at baseline and 1 year, while haptoglobin was lower (p<0.01). LPS was higher (p<0.01) in CSPH patients than in those with subclinical PH and controls and increased at 1-year regardless of decompensation development. ConclusionsInflammation and bacterial products are present in the systemic circulation in compensated cirrhosis with CSPH. Progressive inflammation precedes the first decompensation.