We thank Anja Thiede and Benjamin Maasoumy [1] for adding additional important thoughts on the potential effect of transjugular intrahepatic portosystemic shunt (TIPS) on systemic inflammation (SI) [2,3], highlighting the anti-inflammatory potency of TIPS as being likely higher compared to other treatment options such as non-selective beta-blockers [4,5] a cornerstone for the therapy of clinically significant portal hypertension [6,7]. Just yesterday, the final results from the LIVERHOPE study were published, showing no effect of combined simvastatin 20 mg with rifaximin 1,200 mg on the incidence of acute-on-chronic liver failure or death in patients with decompensated cirrhosis (~80% with ChildPugh B, 90% with previous ascites, but only 37% with ascites grade 2 or 3 at study inclusion) [8]. While only data on Creactive protein (CRP) were shown, these indicated no effect on CRP over the study period or between the simvastatin/rifaximin or placebo groups, which is likely related to a less advanced patient population at study inclusion, as outlined above. Also, median CRP levels were within the normal range at baseline, making any anti-inflammatory effect of such a treatment less likely (compare regression to the mean), acknowledging all limitations of CRP as reflecting the full anti-inflammatory properties of simvastatin/rifaximin. Here, the promising data after TIPS showing a reduction in SI that indeed translated into an improved outcome [9] still give “hope” for a disease-modifying treatment in patients with (refractory) ascites that otherwise suffer from high mortality [10,11], and confirmatory data from randomized controlled trials are eagerly awaited.