Platelet activation and short-term rifaximin therapy in decompensated cirrhosis: a pilot randomized controlled study.

The concept of "rebalanced hemostasis" has improved our understanding of the coexistence of bleeding and thrombosis in cirrhosis. This balance, including changes of platelet function, is easily disrupted by inflammation, through bacterial gut translocation. The modulation of platelet activation through non-absorbable antibiotics remains unexplored. A cross-sectional analysis between patients with decompensated cirrhosis (Child-Pugh, CP, classes B and C) versus age-matched controls without cirrhosis and cardiometabolic diseases was performed to characterize the platelet phenotype and assessed short-term rifaximin effects. Platelet phenotyping, soluble myeloid cells TREM-like transcript-1 (sTLT-1), serum lipopolysaccharides (LPS), inflammatory cytokines, and neutrophil extracellular traps (NETs) markers were quantified. Decompensated cirrhosis patients were randomized to either rifaximin 550 mg BID or placebo for 14 days. Primary outcome was the post-treatment LPS change. Twenty-one patients with decompensated cirrhosis (mean age 59 ± 9 years; 65% male sex, 70% alcohol etiology; mean CP, 7.7 ± 2.2) were matched with sixteen controls (mean age 60 ± 13 years; 37,5% male sex). Patients displayed higher levels of LPS, inflammatory cytokines (IL-1β, IL-6, IL-18, IL-23), and NETs than controls. Platelets from patients with cirrhosis showed significantly lower surface expression of TLT-1 and higher levels of cleaved sTLT-1 (i.e., platelet activation in vivo). Rifaximin did not significantly reduce LPS, inflammatory cytokines, NETosis, and platelet activation. Patients with decompensated cirrhosis exhibit a distinct activation state of platelets with low-grade systemic inflammation and NETosis. Short-term rifaximin failed to reverse these changes, suggesting that longer or combined interventions targeting LPS may be required to rescue platelet dysfunction.