Significance of Serum TGF-β1 Levels for Estimating Bilirubin Decrease Following Biliary Drainage in Jaundiced Patients Caused by Biliary Tract Carcinoma

Abstract

Purpose: Biliary drainage is generally performed in patients with obstructive jaundice (OJ) before major hepatectomy for biliary tract carcinomas. However, estimation of bilirubin decrease rate after biliary drainage may be often difficult. In this study, we investigated useful biochemical marker for estimating a period for bilirubin decrease, and also studied mechanisms responsible for delayed bilirubin reduction. Methods: Peripheral blood samples were taken in 22 patients with OJ caused by biliary tract carcinoma before and after biliary drainage. Serum transforming growth factor-β1 (TGF- β1) and platelet-derived growth factor BB (PDGF-BB), and bilirubin decrease rates (“b”value) were investigated. Expression of desmin and α-smooth muscle actin (α-SMA) in surgically resected liver specimens were also investigated in 12 patients who underwent radical surgery, using immunohistochemical staining, to evaluate hepatic stellate cell (HSC) status. Results: Serum TGF- β1 and PDGF-BB levels were significantly higher in patients with OJ than in controls (p<0.01). Serum levels of total bilirubin and TGF- β1 decreased significantly following biliary drainage. However, bilirubin reduction in patients with high TGF- β1 was significantly slower than those with low TGF- β1, despite of the height of the serum bilirubin levels before drainage. Immunohistochemical studies revealed increased number of HSCs (desmin-positive cells) and activated HSCs (α-SMA-positive cells) in portal areas of the liver in patients with the high TGF- β1 at surgery. Conclusion: Serum TGF- β1 mostly produced by activated HSCs, reflecting hepatic damage by cholestasis, may be a useful biochemical marker for predicting the period of bilirubin reduction in patients with OJ.