Expression of TGF-β1 in liver tissues and its prognostic value of IFN treatment in patients with chronic hepatitis C
摘要
Transforming growth factor-β1 (TGF-β1) is one of the pleiotropic factors that links the inflammatory process to the fibrogenesis. Fat storing cells (FSC) are nonparenchymal liver cells generally considered as the major source of the hepatic extracellular matrices (ECM). The process of the activation and phenotypical modification of FSCs is associated with development of α-smooth muscle actin (α-SMA) microfilaments and a marked increase of ECM synthesis. In this study, we searched for a possible correlation between the expression of TGF-β1 and α-SMA and histological findings in liver biopsy specimens from 32 patients with chronic hepatitis C. In patients who received inteferon (IFN) therapy, we examined the prognostic value of liver TGF-β1 expression analyzed before treatment. Liver biopsy specimens were fixed in acetone-methylbenzoate-xylene, incubated with anti-TGF-β1 antisera (provided from Dr. Kohei Miyazono) and anti-human α-SMA antibody (DAKO), and visualized using the Vectastain ABC kit. The intensity of expression of TGF-β1 and α-SMA in liver tissues was scored from 0 to 3. The histological activity was evaluated according to the scoring system of Scheuer. TGF-β1 was found in activated FSCs in fibroproliferative lesion as well as inside of inflammatory cells. The degree of both TGF-β1 and α-SMA expression was closely correlated with the fibrotic score of Scheuer, respectively. TGF-β1 expression was also correlated with the score of portal/periportal activity. In the investigation of 18 patients treated with IFN, all 7 patients, who had a score of less than 1 in both TGF-β1 and α-SMA expression, showed normal serum ALT levels during IFN treatment. Three of above patients sustained normal ALT levels for more than 6 months after therapy. On the contrary, no effectiveness of IFN therapy was observed in any patients who had a score of more than 3 in both TGF-β1 and α-SMA. These data indicate that the enhanced expression of TGF-β1 is associated with increased numbers of activated FSCs, and that TGF-β1, in this connection, plays a role in stimulating liver fibrogenesis during chronic HCV infection. It is noteworthy that the degree of TGF-β1 expression may be employed as a potent predicting indicator for the therapeutic efficacy of IFN.