Soluble TNF-alpha-receptors I are prognostic markers in TIPS-treated patients with cirrhosis and portal hypertension

PLoS One. 2013 Dec 26;8(12):e83341. doi: 10.1371/journal.pone.0083341. eCollection 2013.


Background: TNFα 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.

Methods: Forty-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.

Results: Before 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.

Conclusion: Hepatic venous levels of sTNFR-I after TIPS insertion may predict mortality in patients with severe portal hypertension.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Biomarkers / blood
  • Blood Chemical Analysis
  • Female
  • Hemodynamics
  • Humans
  • Hypertension, Portal / blood*
  • Hypertension, Portal / etiology*
  • Hypertension, Portal / mortality
  • Hypertension, Portal / surgery
  • Liver Cirrhosis / blood*
  • Liver Cirrhosis / complications*
  • Liver Cirrhosis / mortality
  • Liver Cirrhosis / surgery
  • Male
  • Middle Aged
  • Portal Pressure
  • Portasystemic Shunt, Transjugular Intrahepatic
  • Prognosis
  • Receptors, Tumor Necrosis Factor, Type I / blood*


  • Biomarkers
  • Receptors, Tumor Necrosis Factor, Type I

Grants and funding

The study was supported by grants of Deutsche Forschungsgemeinschaft (SFB TRR57 to P12 and P18), by grants of H. J. & W. Hector Stiftung, as well as by the Capital Region of Denmark Foundation of Health Research and Hvidovre Hospital Foundation for Liver Diseases. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.