Low circulating chemerin levels correlate with hepatic dysfunction and increased mortality in decompensated liver cirrhosis

Paul Horn,Philipp Reuken,Franziska Forkert,Christian Von Loeffelholz,Tony Bruns,Sven Stengel,René Aschenbach,Andreas Stallmach

doi:10.1038/s41598-018-27543-6

Abstract

Nutritional status, infections, inflammation and extrahepatic organ dysfunction are critical factors for the progression of chronic liver disease. Chemerin is an immune-metabolically and chemotactically active adipokine and we hypothesized that it is associated with disease severity and prognosis in patients with advanced decompensated cirrhosis. Therefore, we measured serum concentrations of chemerin in a prospectively characterized cohort of 80 patients with decompensated cirrhosis and ascites and assessed the associations with markers of disease severity and short-term outcome at 28 days. In a subset of patients (n = 40), ascitic fluid chemerin was determined. Advanced liver disease was associated with decreased serum but not ascitic chemerin levels. Serum chemerin correlated with markers of hepatic function (total bilirubin, albumin, INR) and inversely correlated with indicators of portal hypertension (platelet count, gastrointestinal bleeding) but not with extrahepatic organ failure and systemic inflammation. Patients presenting with acute-on-chronic liver failure or infection did not exhibit altered serum or ascitic fluid chemerin concentrations. However, serum chemerin levels below 87 ng/ml predicted an increased risk for mortality or liver transplantation within 28 days independently of MELD and infections. We conclude that low serum chemerin is an independent adverse prognostic factor in patients with advanced decompensated cirrhosis.

Highlights

During the last years, adipokines emerged as multifunctional circulating mediators playing a role in different diseases such as obesity, diabetes mellitus, autoimmune diseases and chronic liver diseases including cirrhosis[1,2,3,4,5,6,7]
Chemerin correlates with necroinflammatory activity and fibrosis in non-alcoholic fatty liver disease (NAFLD) and in viral hepatitis it remains controversial whether chemerin contributes to the pathogenesis of liver disease[16,17,18]
We provide a comprehensive exploratory evaluation of serum concentrations of the immunometabolically active adipokine chemerin as a promising biomarker in decompensated liver disease

Summary

Introduction

Adipokines emerged as multifunctional circulating mediators playing a role in different diseases such as obesity, diabetes mellitus, autoimmune diseases and chronic liver diseases including cirrhosis[1,2,3,4,5,6,7]. Recent data suggest that hepatic chemerin gene expression is reduced in severe non-alcoholic steatohepatitis (NASH)[19] In line with these results, negative associations have been described for chemerin with liver function and disease severity in patients with hepatocellular carcinoma (HCC) and cirrhosis[6,7]. Chemerin as a multifunctional adipokine might serve as a surrogate marker and mediator of different risk factors and complications but associations of chemerin with complications of cirrhosis and extrahepatic organ failure in acute-on-chronic liver failure have not been assessed yet. We determined serum concentrations of chemerin in a well-characterized cohort of 80 patients, who were hospitalized for decompensation of cirrhosis, to determine associations with hepatic and extrahepatic organ failure, bacterial infections, severity of inflammation and short-term prognosis in patients with decompensated liver cirrhosis and severe liver dysfunction. We focused on associations with overall prognosis, hepatic and extrahepatic organ failure, infections and inflammation as well as complications of liver cirrhosis

Methods

Results

Conclusion