Abstract

MircoRNA’s (miR) have been recognised as important modulators of gene expression and potential biomarkers. However, they have been rarely investigated in bio fluids apart from blood. We investigated the association of miR-125b and miR-155 with complications of cirrhosis. Ascites was prospectively collected from patients with cirrhosis undergoing paracentesis at our department. miR’s were determined in the supernatant using qPCR and normalized by SV-40. Clinical parameters were assessed at paracentesis and during follow-up. 76 specimens from 72 patients were analysed. MiR’s were not associated to age, sex or aetiology of cirrhosis. MiR-125b levels differed between patients with low and high MELD score, and miR-125b levels showed an inverse correlation to serum creatinine (r2 = −0.23; p = 0.05). MiR-155 was elevated in patients with spontaneous bacterial peritonitis (SBP) (n = 10; p = 0.04). MiR-155 levels differed between patients with and without 30-day survival (p = 0.02). No association of ascites levels of investigated miR’s to size of varices, episodes of gastrointestinal bleeding or hepatorenal syndrome was observed. While miR-125b levels in ascites seem to be associated with liver and renal dysfunction, miR-155 might be implicated in local immune response in SBP.

Highlights

  • We provide the first data on ascites microRNA levels in chronic liver disease

  • MiR-125b levels were different in patients with high and low model for end-stage liver disease (MELD) as indicator of liver disease severity

  • Because creatinine is one of the three parameters used to calculate the MELD score[25], it is likely that the difference in miR levels between high and low MELD scores did not reflect an association to liver disease severity, but rather the difference in kidney function

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Summary

Patients and Methods

Ascites samples from patients with cirrhosis in whom a diagnostic paracentesis was performed at the Department of Internal Medicine I of the University Bonn were prospectively collected from March 2012 to September 2013. Patient samples were only included if ascites was due to cirrhosis. Diagnosis of cirrhosis was confirmed by liver biopsy, where available, or based on the presence of clinical signs of portal hypertension (oesophageal varices, splenomegaly and ascites), appropriate findings in ultrasound and standard laboratory. Patients who received a liver transplant were considered dead at the day of transplant. Diagnosis of hepatorenal syndrome and grading of esophageal varices was done according to current international guidelines[21,22]. Ascites specimen of patients with cirrhosis were classified according to international guidelines[21] in ascites without infection, SBP or control after SBP. Bacterascites was defined by the detection of bacteria in the presence of a normal ascites PMN count

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