Increased ΤGF-β3 in primary biliary cirrhosis: an abnormality related to pathogenesis?

Abstract

To investigate the transforming growth factor-β (TGF-β) isoforms in the peripheral and hepatic venous blood of primary biliary cirrhosis (PBC) patients. We examined TGF-β1, TGF-β2 and TGF-β3 (enzyme-linked immunosorbent assay), in 27 stage IV PBC patients (27 peripheral and 15 hepatic vein sera), 35 early (I-II) PBC and 60 healthy controls. As disease controls 28 hepatitis C virus (HCV) cirrhosis (28 peripheral and 17 hepatic vein serum), 44 chronic HCV hepatitis and 38 HCV-related hepatocellular carcinomas were included. We also tested liver tissue by immunohistochemistry to identify localization of TGF isoforms. TGF-β1 was significantly decreased in all cirrhotics (PBC III-IV: median 13.4 ng/mL; range, 7.4-26.2, HCV cirrhosis: 11.6 ng/mL; range, 5.0-33.8), compared to controls (30.9 ng/mL; range, 20.9-37.8). TGF-β2 was increased in viral cirrhosis but not in PBC and chronic hepatitis. TGF-β3 (47.2 pg/mL; range, 27.0-79.7 in healthy controls) was increased in early and late PBC (I-II: 94.3 pg/mL; range, 41.5-358.6; III-IV: 152.8 pg/mL; range, 60.4-361.2; P < 0.001) and decreased in viral cirrhosis (37.4 pg/mL; range, 13.3-84.0; P < 0.05). Hepatic vein TGF-β levels were analogous to those in peripheral blood. Immunohistochemistry identified all isoforms in portal tract lymphocytes, sinusoidal cells and cholangiocytes. TGF-β3 was additionally overexpressed in hepatocytes in PBC patients. The serum profile of TGF-β isoforms is different in cirrhotics. Increased TGF-β3 is characteristic of PBC. These findings may be related to the immunological abnormalities of PBC.