Soluble TNF-Alpha-Receptors I Are Prognostic Markers in TIPS-Treated Patients with Cirrhosis and Portal Hypertension

Abstract

BackgroundTNFα levels are increased in liver cirrhosis even in the absence of infection, most likely owing to a continuous endotoxin influx into the portal blood. Soluble TNFα receptors (sTNFR type I and II) reflect release of the short-lived TNFα, because they are cleaved from the cells after binding of TNFα. The aims were to investigate the circulating levels of soluble TNFR-I and -II in cirrhotic patients receiving TIPS.MethodsForty-nine patients with liver cirrhosis and portal hypertension (12 viral, 37 alcoholic) received TIPS for prevention of re-bleeding (n = 14), therapy-refractory ascites (n = 20), or both (n = 15). Portal and hepatic venous blood was drawn in these patients during the TIPS procedure and during the control catheterization two weeks later. sTNFR-I and sTNFR-II were measured by ELISA, correlated to clinical and biochemical characteristics.ResultsBefore TIPS insertion, sTNFR-II levels were lower in portal venous blood than in the hepatic venous blood, as well as in portal venous blood after TIPS insertion. No significant differences were measured in sTNFR-I levels. Hepatic venous levels of sTNFR-I above 4.5 ng/mL (p = 0.036) and sTNFR-II above 7 ng/mL (p = 0.05) after TIPS insertion were associated with decreased survival. A multivariate Cox-regression survival analysis identified the hepatic venous levels of sTNFR-I (p = 0.004) two weeks after TIPS, and Child score (p = 0.002) as independent predictors of mortality, while MELD-score was not.ConclusionHepatic venous levels of sTNFR-I after TIPS insertion may predict mortality in patients with severe portal hypertension.

Increase in liver stiffness after transjugular intrahepatic portosystemic shunt is associated with inflammation and predicts mortality

“…Recently, the close relationship between systemic inflammation, organ failure, ACLF, and mortality has been shown in the CANONIC cohort . Indeed, the increase of liver stiffness after TIPS identified patients developing organ failure and independently predicted mortality in patients receiving TIPS, which is also supported by previous observations of our group ascribing an important prognostic value to inflammatory cytokines …”

IGFBP-3 inhibits TNF-α production and TNFR-2 signaling to protect against Retinal Endothelial Cell Apoptosis

“…These inhibitory effects on the TNFR2 cascade were blocked by treatment with LRP1 siRNA, suggesting that the LRP1 mediates inhibition of the TNF-α receptor-mediated cell death cascade. TNF-α can activate TNFR1 and TNFR2 receptor subtypes, both of which trigger cell death through similar signaling cascades (Leon et al, 2013; Trebicka et al, 2013; Yi et al, 2013). TNFR1 is most commonly associated with cell death in various different cell types, while TNFR2 has been more prominently linked to cell apoptosis in neural tissues (Chen and Palmer, 2013).…”

CXCL9 is a prognostic marker in patients with liver cirrhosis receiving transjugular intrahepatic portosystemic shunt

“…In the first cohort of patients (n = 78), enrolled between 1998 and 2003, a bare TIPS (8-10 mm Wallstent, Boston Scientific, MA, USA) was inserted as previously described [30][31][32][33]. In these patients, after a mean of fourteen days, an invasive procedure was performed to re-evaluate the function and position of the TIPS (previously specified as routine in our centre's protocol to optimize TIPS function) [30][31][32][33].…”

“…In these patients, after a mean of fourteen days, an invasive procedure was performed to re-evaluate the function and position of the TIPS (previously specified as routine in our centre's protocol to optimize TIPS function) [30][31][32][33]. Patients of the second cohort (n = 25), enrolled between 2013 and 2014, received covered TIPS-stents, but no invasive re-evaluation procedure was performed.…”