TIPS insertion leads to sustained reversal of systemic inflammation in patients with decompensated liver cirrhosis.

Background and aims: Systemic Inflammation (SI) is considered a key mechanism in disease progression and development of complications in decompensated liver cirrhosis. SI is mainly driven by portal hypertension and bacterial translocation. Transjugular intrahepatic portosystemic shunt (TIPS)-insertion represents an effective treatment for portal hypertension. This study aims to investigate the impact of TIPS-insertion on SI and bacterial translocation.

Methods: We prospectively included 59 cirrhotic patients undergoing TIPS-insertion. Blood samples were collected at TIPS-insertion and follow-up 1, 3, 6, and 12 months (FU) thereafter. At all time points, we performed a comprehensive analysis of SI including 43 soluble inflammatory markers (SIMs), and surrogates of bacterial translocation (sCD14, sCD163). To investigate long-term kinetics of SI, C-reactive protein (CRP) and white blood cells (WBC) were retrospectively analyzed in a cohort of 177 patients up to 3-years after TIPS-insertion.

Results: At TIPS-insertion, 30/43 SIMs, sCD14, and sCD163 measured significantly higher in cirrhotic patients compared to healthy controls. By FU6 25 SIMs and sCD14 measured at significantly lower levels compared to baseline. Interestingly, in patients with TIPS-indication refractory ascites IL-6 decreased to levels documented in earlier stages of cirrhosis. In long-term follow-up, CRP-levels significantly decreased after TIPS-insertion, which translated into improved liver-transplant-free survival in cox regression analysis (HR 0.968, p=0.042). Notably, patients with residual ascites post-TIPS showed significantly higher CRP- and IL-6 levels across all follow-ups compared to patients with resolved ascites.

Conclusions: Decreasing portal hypertension via TIPS-insertion leads to a significant attenuation of SI and bacterial translocation over time.