Abstract
BackgroundAutotaxin (ATX) and its product lysophosphatidic acid (LPA) are considered to be involved in the development of liver fibrosis and elevated levels of serum ATX have been found in patients with hepatitis C virus associated liver fibrosis. However, the clinical role of systemic ATX in the stages of liver cirrhosis was unknown. Here we investigated the relation of ATX serum levels and severity of cirrhosis as well as prognosis of cirrhotic patients.MethodsPatients with liver cirrhosis were prospectively enrolled and followed until death, liver transplantation or last contact. Blood samples drawn at the day of inclusion in the study were assessed for ATX content by an enzyme-linked immunosorbent assay. ATX levels were correlated with the stage as well as complications of cirrhosis. The prognostic value of ATX was investigated by uni- and multivariate Cox regression analyses. LPA concentration was determined by liquid chromatography-tandem mass spectrometry.Results270 patients were enrolled. Subjects with liver cirrhosis showed elevated serum levels of ATX as compared to healthy subjects (0.814±0.42 mg/l vs. 0.258±0.40 mg/l, P<0.001). Serum ATX levels correlated with the Child-Pugh stage and the MELD (model of end stage liver disease) score and LPA levels (r = 0.493, P = 0.027). Patients with hepatic encephalopathy (P = 0.006), esophageal varices (P = 0.002) and portal hypertensive gastropathy (P = 0.008) had higher ATX levels than patients without these complications. Low ATX levels were a parameter independently associated with longer overall survival (hazard ratio 0.575, 95% confidence interval 0.365–0.905, P = 0.017).ConclusionSerum ATX is an indicator for the severity of liver disease and the prognosis of cirrhotic patients.
Highlights
Liver cirrhosis is the result of chronic injury and fibrotic remodeling of the liver [1]
270 patients with liver cirrhosis were prospectively included in this study
Alcohol abuse and chronic HCV infection were the predominant causes for liver cirrhosis in this cohort. 199 patients showed signs of hepatic decompensation at the time of inclusion in the study
Summary
Liver cirrhosis is the result of chronic injury and fibrotic remodeling of the liver [1]. A connection between liver fibrosis and serum or plasma LPA and ATX emerged in patients with chronic HCV infection [17,18]. We assessed if serum ATX levels might be associated with specific complications of liver cirrhosis as well as overall survival (OS). To this end we performed a prospective cohort study in patients with liver cirrhosis, assessed the serum ATX levels and correlated them with the prevalence of complications and OS. Autotaxin (ATX) and its product lysophosphatidic acid (LPA) are considered to be involved in the development of liver fibrosis and elevated levels of serum ATX have been found in patients with hepatitis C virus associated liver fibrosis. We investigated the relation of ATX serum levels and severity of cirrhosis as well as prognosis of cirrhotic patients
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