Portal levels of latent transforming growth factor-β are related to liver function in patients with liver cirrhosis

Abstract

Transforming growth factor-β1 (TGFβ1) is a short-lived immune suppressive and profibrotic protein. Its latent precursor is relatively stable and may even protect from fibrosis. Latent TGFβ1 is synthesized by various tissues including the liver and portal, hepatic, and systemic concentrations of latent TGFβ1 were determined in patients with liver cirrhosis and patients with normal liver function to find out whether circulating levels are affected by liver disease. Latent TGFβ1 was measured in portal venous serum (PVS), hepatic venous serum (HVS), and systemic venous serum (SVS) of 26 patients with liver cirrhosis and nine patients with normal liver function. Latent TGFβ1 was similarly abundant in HVS, PVS,and SVS of patients with liver cirrhosis and controls. There was a strong positive correlation of HVS, PVS, and SVS TGFβ1 to each other. PVS levels of latent TGFβ1 were significantly lower in patients with CHILD-PUGH stage C compared with CHILD-PUGH stage A, SVS levels were modestly and HVS levels tended to be reduced. PVS and SVS TGFβ1 concentrations were also lower in patients with a higher model for end-stage liver disease score. Only PVS concentrations were reduced in patients with massive ascites compared with the patients without ascites. Creatinine clearance as a marker of renal function and parameters of coagulation did not correlate with this cytokine indicating that latent TGFβ1 levels are not linked to kidney function and coagulation. Interleukin-6, which is elevated in patients with liver cirrhosis negatively correlated with latent TGFβ1 in PVS and SVS. In patients with liver cirrhosis splanchnic organ-derived latent TGFβ1 is negatively associated with the liver function.