The role of miRNA-34a as a prognostic biomarker for cirrhotic patients with portal hypertension receiving TIPS

PLoS One. 2014 Jul 28;9(7):e103779. doi: 10.1371/journal.pone.0103779. eCollection 2014.

Abstract

Background: Circulating miRNA-34a is increased in blood of patients with different liver diseases when compared to healthy controls. However, the origin of miRNA-34a and its possible relationship with hemodynamics and outcome in cirrhotic patients with portal hypertension is unknown. We analyzed the levels of miRNA-34a in cirrhotic patients with severe portal hypertension.

Methods: We included 60 cirrhotic patients receiving TIPS for prevention of rebleeding and/or therapy-refractory ascites. miRNA-34a levels were measured using qPCR and normalized by SV-40 in the portal and hepatic venous blood of these patients taken at TIPS procedure. Hemodynamic and clinical parameters were assessed before TIPS and during follow-up.

Results: Levels of miRNA-34a were higher in the hepatic vein than in the portal vein. Circulating miRNA-34a in the hepatic vein correlated with ALT, CHE and sodium excretion after TIPS. miRNA-34a showed no correlation with portal pressure, but its levels in the portal vein correlated inversely with the congestion index. Interestingly, the levels of miRNA-34a in the portal and hepatic vein showed inverse correlation with arterial pressure. Furthermore, levels of miRNA-34a in the hepatic vein had a predictive value for survival, but MELD, creatinine at short-time follow-up 14 days after TIPS-insertion and portal pressure after TIPS performed better.

Conclusion: This study demonstrates for the first time, that miRNA-34a may originate to a large extent from the liver. Even though higher levels of miRNA-34a are possibly associated with better survival at long-term follow-up in cirrhotic patients with severe portal hypertension receiving TIPS, classical prognostic parameters predict the survival better.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Biomarkers / blood*
  • Female
  • Gene Expression
  • Hepatic Veins / metabolism
  • Humans
  • Hypertension, Portal / diagnosis*
  • Hypertension, Portal / genetics
  • Hypertension, Portal / surgery
  • Kaplan-Meier Estimate
  • Liver Cirrhosis / diagnosis*
  • Liver Cirrhosis / genetics
  • Liver Cirrhosis / surgery
  • Male
  • MicroRNAs / blood*
  • MicroRNAs / genetics
  • Middle Aged
  • Outcome Assessment, Health Care / methods
  • Outcome Assessment, Health Care / statistics & numerical data
  • Portal Vein / metabolism
  • Portasystemic Shunt, Transjugular Intrahepatic
  • Prognosis
  • Proportional Hazards Models
  • Retrospective Studies
  • Reverse Transcriptase Polymerase Chain Reaction

Substances

  • Biomarkers
  • MIRN34 microRNA, human
  • MicroRNAs

Grant support

The study was supported by grants from Deutsche Forschungsgemeinschaft (SFB TRR57 P18 to J.T./T.S.) and from J. & W. Hector-Foundation (to J.T.). This study was further supported by the Research and Education program of the Medical Faculty of the University of Cologne and funded by the German Ministry of Education and Research (BMBF), Grant No. 01KI0601 (to M.O.) and the German Liver Foundation (to M.O). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.